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Sample records for 25-oh-cholesterol pregnenolone progesterone

  1. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor.

    PubMed

    Craig, Zelieann R; Hannon, Patrick R; Flaws, Jodi A

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P4) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P4, androstenedione (A), testosterone (T), estrone (E1), and 17β-estradiol (E2) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E2. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P4, A, T, and E1 that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival.

  2. Stimulatory effects of propylthiouracil on pregnenolone production through upregulation of steroidogenic acute regulatory protein expression in rat granulosa cells.

    PubMed

    Chen, Mei-Chih; Wang, Shyi-Wu; Kan, Shu-Fen; Tsai, Shiow-Chwen; Wu, Yu-Ching; Wang, Paulus S

    2010-12-01

    Propylthiouracil (PTU) is a common and effective clinical medicine for the treatment of hyperthyroidism. Our previous study demonstrated that short-term treatment with PTU inhibits progesterone production in rat granulosa cells. However, our present results indicate that a 16-h treatment with PTU was able to stimulate pregnenolone production in rat granulosa cells, although progesterone production was diminished by PTU through inhibition of 3β-hydroxysteroid dehydrogenase. Notably, we found that PTU treatment enhanced the conversion of cholesterol into pregnenolone, whereas the protein level of the cytochrome P450 side-chain cleavage enzyme (P450scc, which is the enzyme responding to this conversion) was not affected. Interestingly, the levels of steroidogenic acute regulatory protein (StAR) in both total cell lysate and the mitochondrial fraction were significantly increased by PTU treatment. Furthermore, the binding of steroidogenic factor-1 (SF-1) to the StAR promoter region was also enhanced by PTU treatment, which suggests that PTU could upregulate StAR gene expression. In addition to SF-1 regulation, we found that mitogen-activated protein (MAP) kinase kinase activation is an important regulator of PTU-stimulated StAR protein expression, based on the effects of the MEK inhibitor PD98059. In conclusion, these results indicate that PTU plays opposite roles in the production of progesterone and its precursor, pregnenolone. The regulation of negative feedback on speeding the cholesterol transportation and pregnenolone conversion after a 16-h PTU treatment may be the mechanism explaining PTU's inhibition of progesterone production in rat granulosa cells.

  3. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    SciTech Connect

    Craig, Zelieann R. Hannon, Patrick R. Flaws, Jodi A.

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17β-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis

  4. Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone

    SciTech Connect

    Hu, Z.Y.; Bourreau, E.; Jung-Testas, I.; Robel, P.; Baulieu, E.E.

    1987-12-01

    Oligodendrocyte mitochondria from 21-day-old Sprague-Dawley male rats were incubated with 100 nM (/sup 3/H)cholesterol. It yielded (/sup 3/H)pregnenolone at a rate of 2.5 +/- 0.7 and 5-(/sup 3/H)pregnene-3..beta..,20..cap alpha..-diol at a rate of 2.5 +/- 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19- to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with (/sup 3/H)mevalonolactone. (/sup 3/H)Cholesterol, (/sup 3/H)pregnenolone, and 5-(/sup 3/H)pregnene-3..beta..,20..cap alpha..-diol were characterized in cellular extracts. The formation of the /sup 3/H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of neurosteroids applied to ..delta../sup 5/-3..beta..-hydroxysteroids previously isolated from brain.

  5. Pregnenolone functions in centriole cohesion during mitosis.

    PubMed

    Hamasaki, Mayumi; Matsumura, Shigeru; Satou, Ayaka; Takahashi, Chisato; Oda, Yukako; Higashiura, Chika; Ishihama, Yasushi; Toyoshima, Fumiko

    2014-12-18

    Cell division is controlled by a multitude of protein enzymes, but little is known about roles of metabolites in this mechanism. Here, we show that pregnenolone (P5), a steroid that is produced from cholesterol by the steroidogenic enzyme Cyp11a1, has an essential role in centriole cohesion during mitosis. During prometa-metaphase, P5 is accumulated around the spindle poles. Depletion of P5 induces multipolar spindles that result from premature centriole disengagement, which are rescued by ectopic introduction of P5, but not its downstream metabolites, into the cells. Premature centriole disengagement, induced by loss of P5, is not a result of precocious activation of separase, a key factor for the centriole disengagement in anaphase. Rather, P5 directly binds to the N-terminal coiled-coil domain of short-form of shugoshin 1 (sSgo1), a protector for centriole cohesion and recruits it to spindle poles in mitosis. Our results thus reveal a steroid-mediated centriole protection mechanism.

  6. The Fungus Trichoderma Regulates Submerged Conidiation Using the Steroid Pregnenolone.

    PubMed

    Lin, Hui; Travisano, Michael; Kazlauskas, Romas J

    2016-09-16

    In previous work, we evolved a population of Trichoderma citrinoviride in liquid cultures to speed up its asexual development cycle. The evolved population, called T-6, formed conidia 3 times sooner and in >1000-fold greater numbers. Here, we identify the steroid pregnenolone as a molecular signal for this different behavior. Media in which the ancestral T. citrinoviride population was grown (called ancestral spent media) contained a submerged conidiation inhibitor. Growing the evolved population T-6 in ancestral spent media eliminated the abundant formation of conidia. This inhibition depended on the amount and age of the ancestral spent medium and the time that the ancestral spent medium was added to the T-6 culture. Fractionation of the ancestral spent medium identified a hydrophobic inhibiting compound with a molecular weight less than 2000 g/mol. A combination of GC-MS, ELISA, and reaction with cholesterol oxidase identified it as pregnenolone. The addition of pregnenolone to cultures of T-6 inhibited submerged conidiation by inhibiting formation of conidiophores, while 10 other analogous steroids did not. Pregnenolone also inhibited submerged conidiation of Fusarium graminearum PH-1, a plant pathogen that causes head blight in wheat and barley. This identification of steroids as signal molecules in fungi creates opportunities to disrupt this signaling to control fungal behavior. PMID:27413801

  7. Steroidogenesis in plants--Biosynthesis and conversions of progesterone and other pregnane derivatives.

    PubMed

    Lindemann, Peter

    2015-11-01

    In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain-cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed. PMID:26282543

  8. Steroidogenesis in plants--Biosynthesis and conversions of progesterone and other pregnane derivatives.

    PubMed

    Lindemann, Peter

    2015-11-01

    In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain-cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed.

  9. Progesterone and 5 beta-pregnanediol production by isolated fetal placental binucleate cells from sheep and goats.

    PubMed

    Wango, E O; Heap, R B; Wooding, F B

    1991-05-01

    Enzymic dispersion and density gradient separation were used for the isolation of enriched populations (60-90%) of cells from the corpus luteum, placenta and peripheral blood of pregnant sheep and goats. Analysis of the steroids produced from radioactive pregnenolone demonstrated that placental binucleate cells can produce progesterone and 5 beta-pregnanediol whereas white blood cells were relatively inactive. Thus, sheep binucleate cells converted pregnenolone predominantly to progesterone as did sheep luteal cells. However, goat binucleate cells produced 5 beta-pregnanediol as the major metabolite, which is consistent with its production in vivo during pregnancy. Production of progesterone (sheep) or 5 beta-pregnanediol (goat) by binucleate cells was shown to be proportional to the number and viability of the cells. In contrast with the binucleate cells there was no evidence that trophectodermal uninucleate cells play a significant role in placental progesterone or 5 beta-pregnanediol synthesis in either species. PMID:2040862

  10. Molecular mechanism of reduction in pregnenolone synthesis by cigarette smoke

    SciTech Connect

    Bose, Mahuya; Whittal, Randy M.; Gairola, C. Gary; Bose, Himangshu S.

    2008-05-15

    Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol from the outer to inner mitochondrial membrane for the synthesis of pregnenolone. Here, we investigated the molecular mechanism of the reduction of pregnenolone synthesis by cigarette smoke condensate (CSC). Pre-exposure or post-exposure of cells with CSC led to reduced pregnenolone synthesis, in a fashion similar to its effect on isolated mitochondria. However, there was no difference in the expression of 30 kDa StAR in cells treated with moderately concentrated CSC by either regimen. The active form of 37 kDa StAR is degraded easily suggesting that the continuous presence of CSC reduces StAR expression. Mitochondrial import of {sup 35}S-methionine-labeled StAR followed by extraction of the StAR-mitochondrial complex with 1% digitonin showed similarly sized complexes in the CSC-treated and untreated mitochondria. Further analysis by sucrose density gradient centrifugation showed a specific complex, 'complex 2', in the untreated mitochondria but absent in the CSC-treated mitochondria. Mass spectrometric analysis revealed that complex 2 is the outer mitochondrial protein, VDAC1. Knockdown of VDAC1 expression by siRNA followed by co-transfection with StAR resulted in a lack of pregnenolone synthesis and 37 kDa StAR expression with reduced expression of the intermediate, 32 kDa StAR. Taken together, these results suggest that in the absence of VDAC1, active StAR expression is reduced indicating that VDAC1 expression is essential for StAR activity. In the absence of VDAC1-StAR interaction, cholesterol cannot be transported into mitochondria; thus the interaction with VDAC1 is a mandatory step for initiating steroidogenesis.

  11. Pregnenolone sulfate as a modulator of synaptic plasticity

    PubMed Central

    Smith, Conor C.; Gibbs, Terrell T.

    2015-01-01

    Rationale The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years. Objectives New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update. Results Highly specific actions of PregS affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission and the pharmacological effects of PregS on various receptors and ion channels are discussed. The discovery of a high potency (nanomolar) signal transduction pathway for PregS-induced NMDAR trafficking to the cell surface via a Ca2+- and G protein-coupled receptor (GPCR)-dependent mechanism and a potent (EC50 ~2 pM) direct enhancement of intracellular Ca2+ levels is discussed in terms of its agonist effects on long-term potentiation (LTP) and memory. Lastly, preclinical and clinical studies assessing the promnestic effects of PregS and pregnenolone toward cognitive dysfunction in schizophrenia, and altered serum levels in epilepsy and alcohol dependence, are reviewed. Conclusions PregS is present in human and rodent brain at physiologically relevant concentrations and meets most of the criteria for an endogenous neurotransmitter/neuromodulator. PregS likely plays a significant role in modulation of glutamatergic excitatory synaptic transmission underlying learning and memory, yet the molecular target(s) for its action awaits identification. PMID:24997854

  12. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

    PubMed

    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.

  13. Promnestic effects of intranasally applied pregnenolone in rats.

    PubMed

    Abdel-Hafiz, Laila; Chao, Owen Y; Huston, Joseph P; Nikolaus, Susanne; Spieler, Richard E; de Souza Silva, Maria A; Mattern, Claudia

    2016-09-01

    The neurosteroid pregnenolone (PREG) has been shown to have memory-enhancing and anti-depressant action. The present study addresses the question of whether intranasally applied pregnenolone (IN-PREG) also has promnestic properties in the rat. We examined the effects of IN-PREG at doses of 0.187 and 0.373mg/kg on memory for objects and their location on learning and retention of escape in a water maze, and on behavior on the elevated plus maze. The main findings were: (a) Pre-trial, but not post-trial, administration of IN-PREG facilitated long-term memory in a novel object-preference test and a novel object-location preference test when tested 48h after dosing. (b) Over the duration of 5days of extinction trials, after learning to escape onto a hidden platform in a water maze, the animals treated with IN-PREG spent more time in searching for the absent platform, indicating either, or both, superior memory for the former position of the escape platform, or a higher resistance to extinction. (c) Administration of the anticholinergic, scopolamine, disrupted learning to escape from the water maze in the vehicle-treated group. The IN-PREG treated groups exhibited superior escape learning in comparison with vehicle controls, indicating that the treatment countered the scopolamine effect. IN-PREG treatment had no influence on behaviors on the elevated plus maze. Our results demonstrate that IN-PREG is behaviorally active with cognitive enhancing properties comparable to those known from studies employing systemic PREG administration. PMID:27423520

  14. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system

    SciTech Connect

    Strushkevich, Natallia; MacKenzie, Farrell; Cherkesova, Tatyana; Grabovec, Irina; Usanov, Sergey; Park, Hee-Won

    2011-09-06

    In humans, the precursor to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1). This complex not only plays a key role in steroidogenesis, but also has long been a model to study electron transfer, multistep catalysis, and C-C bond cleavage performed by monooxygenases. Detailed mechanistic understanding of these processes has been hindered by a lack of structural information. Here we present the crystal structure of the complex of human Adx and CYP11A1 - the first of a complex between a eukaryotic CYP and its redox partner. The structures with substrate and a series of reaction intermediates allow us to define the mechanism underlying sequential hydroxylations of the cholesterol and suggest the mechanism of C-C bond cleavage. In the complex the [2Fe-2S] cluster of Adx is positioned 17.4 {angstrom} away from the heme iron of CYP11A1. This structure suggests that after an initial protein-protein association driven by electrostatic forces, the complex adopts an optimized geometry between the redox centers. Conservation of the interaction interface suggests that this mechanism is common for all mitochondrial P450s.

  15. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression

    PubMed Central

    Brown, E Sherwood; Park, John; Marx, Christine E; Hynan, Linda S; Gardner, Claire; Davila, Domingo; Nakamura, Alyson; Sunderajan, Prabha; Lo, Alexander; Holmes, Traci

    2014-01-01

    Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology—Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ2(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=−0.43, p=0.036) and pregNANolone (r(22)=−0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered. PMID:24917198

  16. Astrocytes and neurosteroids: metabolism of pregnenolone and dehydroepiandrosterone. Regulation by cell density

    PubMed Central

    1993-01-01

    The rat central nervous system (CNS) has previously been shown to synthesize pregnenolone (PREG) and convert it to progesterone (PROG) and 7 alpha-hydroxy-PREG (7 alpha-OH PREG). Astrocytes, which participate to the regulation of the CNS function, might be involved in the metabolism of neurosteroids. Purified type 1 astrocytes were obtained from fetal rat forebrain with the use of selective culture conditions and were identified by immunostaining with specific antibodies (GFAP+, A2B5-). They were plated at low, intermediate, or high densities (2.5-5 x 10(5), 1-2 x 10(6), or 4-8 x 10(6) cells/dish, respectively) and maintained for 21 d. They were then incubated with 14C-PREG and 14C-DHEA for 24 h and the steroids extracted from cells and media were analyzed. Most radioactive derivatives were released into incubation media. Two metabolic pathways were mainly observed. PREG and DHEA were oxidized to PROG and androstenedione (ADIONE), respectively, [3 beta-hydroxysteroid-dehydrogenase, delta 5-->4 3- ketosteroid-isomerase (3 beta-HSD) activity], and converted to 7 alpha- OH PREG and 7 alpha-OH DHEA, respectively (7 alpha-hydroxylase activity). After low density plating, the formation of PROG and ADIONE was approximately 10% of incubated radioactivity, tenfold larger than that of 7 alpha-hydroxylated metabolites. In contrast, after high density plating, low levels of PROG and ADIONE were formed, whereas the conversion to either 7 alpha-OH PREG or 7 alpha-OH DHEA was > or = 50%. The results expressed per cell indicated that the 3 beta-HSD activity was almost completely inhibited at high cell density, in contrast to the 7 alpha-hydroxylation which was maintained or increased. The pattern of steroid metabolism was related to cell density at the time of measurement and not to an early commitment of cells: when primary cultures were plated at high density (8 x 10(6) cells/dish), then subcultured after several dilutions (3-, 9-, or 27-fold), the 3 beta- HSD activity was

  17. Prostate Androgen-Regulated Mucin-Like protein 1: A Novel Regulator of Progesterone Metabolism

    PubMed Central

    Park, Ji Yeon; Jang, Hyein; Curry, Thomas E.; Sakamoto, Aiko

    2013-01-01

    The LH surge reprograms preovulatory follicular cells to become terminally differentiated luteal cells which produce high levels of progesterone and become resistant to apoptosis. PARM1 (prostate androgen regulated mucin-like protein 1) has been implicated in cell differentiation and cell survival in nonovarian cells, but little is known about PARM1 in the ovary. This study demonstrated that the LH surge induced a dramatic increase in Parm1 expression in periovulatory follicles and newly forming CL in both cycling and immature rat models. We further demonstrated that hCG increases Parm1 expression in granulosa cell cultures. The in vitro up-regulation of Parm1 expression was mediated by hCG-activated multiple signaling pathways and transcriptional activation of this gene. Parm1 knockdown increased the viability of cultured granulosa cells but resulted in a decrease in progesterone levels. The inhibitory effect of Parm1 silencing on progesterone was reversed by adenoviral mediated add-back expression of Parm1. Parm1 silencing had little effect on the expression of genes involved in progesterone biosynthesis and metabolism such as Scarb1, Ldlr, Vldlr, Scp2, Star, Cyp11a1, Hsd3b, and Srd5a1, while decreasing the expression of Akr1c3. Analyses of culture media steroid levels revealed that Parm1 knockdown had no effect on pregnenolone levels, while resulting in time-dependent decreases in progesterone and 20α-dihydroprogesterone and accelerated accumulation of 5α-pregnanediol. This study revealed that the up-regulation of Parm1 expression promotes progesterone and 20α-dihydroprogesterone accumulation in luteinizing granulosa cells by inhibiting progesterone catabolism to 5α-pregnanediol. PARM1 contributes to ovulation and/or luteal function by acting as a novel regulator of progesterone metabolism. PMID:24085821

  18. Determination of progesterone and some of its neuroactive ring A-reduced metabolites in human serum.

    PubMed

    Pearson Murphy, B E; Allison, C M

    2000-10-01

    A method for the separation and assay of some ring A-reduced metabolites of progesterone (pregnanediones and pregnanolones) is described. Serum was extracted with an organic solvent, and the extract chromatographed using high performance liquid chromatography (HPLC). A total of 50 fractions was collected for each sample and split using a stream splitter so that 30% was collected in counting vials for recovery while 70% was collected in test tubes which were assayed by radioimmunoassay. An antiserum raised in our laboratory to progesterone-3-CMO-BSA cross-reacted with five of these compounds (5alpha- and 5beta-dihydroprogesterone, 3alpha- and 3beta-5alpha-tetrahydroprogesterone, and 3beta, 5beta-tetrahydroprogesterone). Since pregnenolone eluted with 5alpha, 3beta-tetrahydroprogesterone, pregnenolone was assayed separately and its effect subtracted. Using this method it was shown that picogram to nanogram/ml amounts of these metabolites are present in all human sera. Levels in men were comparable to those of women in the follicular phase of the menstrual cycle. 5alpha-Dihydroprogesterone and 3alpha,5alpha-tetrahydroprogesterone rose substantially in the luteal phase of the menstrual cycle and all rose considerably during pregnancy.

  19. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions

    PubMed Central

    2012-01-01

    Background Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Methods Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose–response study. The highest tested concentration of NE (10 (−7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (−8) M), a non-selective beta-adrenergic antagonist. Conclusions The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation. PMID:23171052

  20. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    PubMed Central

    Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD. PMID:24849255

  1. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder.

    PubMed

    Fung, Lawrence K; Libove, Robin A; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y

    2014-11-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.

  2. Effects of progesterone and norethindrone on female fathead minnow (Pimephales promelas) steroidogenesis.

    PubMed

    Petersen, Lene H; Hala, David; Carty, Dennis; Cantu, Mark; Martinović, Dalma; Huggett, Duane B

    2015-02-01

    As knowledge of contaminants capable of adversely modulating endocrine functions increases, attention is focused on the effects of synthetic progestins as environmental endocrine disrupters. In the present study, effects of exposure to a synthetic progestin (norethindrone, 168 ± 7.5 ng/L) and endogenous progestogen (progesterone, 34 ± 4.1 ng/L) on steroidogenesis in adult female fathead minnows were examined. In vivo exposure to either compound lowered expression (nonsignificant) of luteinizing hormone (LHβ) levels in the brain along with significantly down-regulating the beta isoform of membrane progesterone receptor (mPRβ) in ovary tissue. The correspondence between lowered LHβ levels in the brain and mPRβ in the ovary is suggestive of a possible functional association as positive correlations between LHβ and mPR levels have been demonstrated in other fish species. In vitro exposure of ovary tissue to progesterone resulted in significantly elevated progestogen (pregnenolone, 17α-hydroxyprogesterone, and 17α,20β-dihydroxypregnenone) and androgen (testosterone) production. Whereas in vitro exposure to norethindrone did not significantly impact steroid hormone production but showed decreased testosterone production relative to solvent control (however this was not significant). Overall, this study showed that exposure to a natural progestogen (progesterone) and synthetic progestin (norethindrone), was capable of modulating LHβ (in brain) and mPRβ expression (in ovary). PMID:25470578

  3. Progesterone Receptor Signaling Mechanisms.

    PubMed

    Grimm, Sandra L; Hartig, Sean M; Edwards, Dean P

    2016-09-25

    Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. This paper summarizes recent advances in understanding the structure-function properties of the receptor protein and the tissue/cell-type-specific PR signaling pathways that contribute to the biological actions of progesterone in the normal breast and in breast cancer. PMID:27380738

  4. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

  5. Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits

    PubMed Central

    Sripada, Rebecca K.; Marx, Christine E.; King, Anthony P.; Rampton, Jessica C.; Ho, Shaun; Liberzon, Israel

    2013-01-01

    Background The neurosteroid allopregnanolone is a potent allosteric modulator of the GABA(A) receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective functioning. However, the neural mechanism whereby allopregnanolone improves mood and reduces anxiety is unknown. In particular, brain imaging has not been used to link neurosteroid effects to emotion regulation neurocircuitry. Methods To investigate the brain basis of allopregnanolone’s impact on emotion regulation, participants were administered 400mg of pregnenolone (N=16) or placebo (N=15) and underwent 3T fMRI while performing the Shifted-Attention Emotion Appraisal Task (SEAT), which probes emotional processing and regulation. Results Compared to placebo, allopregnanolone was associated with reduced activity in the amygdala and insula across all conditions. During the appraisal condition, allopregnanolone increased activity in the dorsal medial prefrontal cortex and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, an effect that was associated with reduced self-reported anxiety. Conclusions These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacological intervention in the treatment of anxiety disorders, and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry. PMID:23348009

  6. 21 CFR 556.540 - Progesterone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Progesterone. 556.540 Section 556.540 Food and... Residues of New Animal Drugs § 556.540 Progesterone. No residues of progesterone are permitted in excess of the following increments above the concentrations of progesterone naturally present in...

  7. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

    Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations. PMID:22193289

  8. Inhibition of basal and stimulated progesterone synthesis by dichlorodiphenyldichloroethylene and methoxychlor in a stable pig granulosa cell line.

    PubMed

    Crellin, N K; Kang, H G; Swan, C L; Chedrese, P J

    2001-03-01

    The effects of the insecticide dichlorodiphenyldichloroethylene (DDE) and methoxychlor in a stable pig granulosa cell line, JC-410, were investigated. The studies of DDE and methoxychlor were conducted in combination with studies of cholera toxin, the protein kinase A activator that stimulates cAMP and progesterone synthesis and gene expression of P450 cholesterol side chain cleavage (P450scc), which converts cholesterol to pregnenolone. Administration of DDE at 3000 and 10 000 ng ml (-1) was found to decrease progesterone synthesis 0.49- and 0.25-fold, respectively, and to block the stimulatory effect of 100 ng cholera toxin ml (-1), after 24 h incubation. At 1-100 ng ml (-1), methoxychlor did not affect progesterone synthesis after 48 h incubation. However, 1000 ng methoxychlor ml (-1) decreased progesterone synthesis 0.32-fold, and both 100 and 1000 ng methoxychlor ml (-1) blocked the stimulatory effect of cholera toxin. At 3000 and 10 000 ng ml(-1), DDE decreased cAMP synthesis 0.66-and 0.36-fold, respectively. At 300, 3000 and 10 000 ng ml (-1), DDE also decreased cholera toxin-stimulated cAMP synthesis 0.84-, 0.68-, and 0.52-fold, respectively. Administration of 1-100 ng methoxychlor ml (-1) did not affect basal or cholera toxin-stimulated cAMP synthesis. Cholera toxin increased P450scc mRNA 1.4-fold after 24 h incubation, while 3000 and 10 000 ng DDE ml (-1) led to 0.39- and 0.18-fold reductions, respectively. The stimulatory effect of cholera toxin on P450scc mRNA was blocked by 3000 and 10 000 ng DDE ml(-1). Cholera toxin increased P450scc mRNA 3.48-fold after 48 h incubation, while 100 and 1000 ng methoxychlor ml (-1) increased P450scc mRNA 1.79- and 3.0-fold, respectively, and further increased the stimulatory effect of cholera toxin 6.47- and 5.44-fold, respectively. The results of the present study indicate that DDE inhibits granulosa cell steroidogenesis by affecting cAMP production and P450scc gene expression. However, methoxychlor appears to inhibit

  9. Progesterone vaginal ring for luteal support.

    PubMed

    Stadtmauer, Laurel; Waud, Kay

    2015-02-01

    Progesterone supplementation is universally used and has been shown to be beneficial in supplementation of the luteal phase in IVF. There are multiple options and the most commonly used include intramuscular and vaginal progesterone. A progesterone vaginal ring is a novel system for luteal support with advantages of controlled release with less frequent dosing. This review examines options for progesterone luteal support focusing on the rationale for a progesterone vaginal ring. Pub-med search of the literature. A weekly vaginal ring, although not yet FDA approved, is an effective and safe alternative for luteal supplementation in IVF. Large prospective clinical trials are needed to determine the best protocols for replacement cycles.

  10. Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R.; Febo, Marcelo; Li, Mona; Gold, Mark S.

    2015-01-01

    Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction, and intoxication. Some research into those harms will be reviewed here and misgivings about the use of Pregnenolone, to treat cannabis addiction and intoxication explained. Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication. The major active ingredient of Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor. This steroid has been shown to inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. In this hypothesis, we caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation. Blocking CB1 receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling. Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels, may induce a hypodopaminergic state, and lead to aberrant substance and non-substance (behavioral) addictions. PMID:26306328

  11. The roles of pregn-5-ene-3β,20α-diol and 20α-hydroxy steroid dehydrogenase in the control of progesterone synthesis preceding parturition and lactogenesis in the rat

    PubMed Central

    Kuhn, N. J.; Briley, M. S.

    1970-01-01

    1. The activity of 20α-hydroxy steroid dehydrogenase in rat ovarian corpora lutea increased at least 50-fold between 2 days before and 2 days after parturition, and then fell gradually during lactation. The activity of 3β-hydroxy Δ5-steroid dehydrogenase decreased by 50% at parturition but remained constant at other times. 2. The 20α-hydroxypregn-4-en-3-one/progesterone concentration ratio in the ovary fell tenfold between 1 day before and 1 day after parturition, in contrast with the increase of the ratio for these steroids in plasma. 3. Pregnenolone was metabolized in intact cells or cell-free systems either to pregn-5-ene-3β,20α-diol and then to 20α-hydroxypregn-4-en-3-one by 20α-hydroxy steroid dehydrogenase and 3β-hydroxy Δ5-steroid dehydrogenase respectively, or directly to progesterone by the latter enzyme. The relative activities of these pathways appeared to reflect the relative amounts of the two enzymes and the concentrations of their respective coenzymes NADPH and NAD+. 4. From these and other observations it was concluded that the cessation of progesterone secretion, which precedes parturition and lactogenesis at the end of pregnancy, is partly due to the redirected metabolism of pregnenolone away from progesterone and towards 20α-hydroxypregn-4-en-3-one as the secreted end product. This is primarily the consequence of the sharp increase in the activity of 20α-hydroxy steroid dehydrogenase. This mechanism is super-imposed on the already declining rate of net Δ4-steroid release by the ovary. 5. A relationship of these pathways to subcellular compartments of luteal cells is proposed. PMID:4392955

  12. Pregnenolone sulfate and its enantiomer: differential modulation of memory in a spatial discrimination task using forebrain NMDA receptor deficient mice

    PubMed Central

    Petit, Géraldine H.; Tobin, Christine; Krishnan, Kathiresan; Moricard, Yves; Covey, Douglas F.; Rondi-Reig, Laure; Akwa, Yvette

    2010-01-01

    This study examined the role of forebrain N-methyl-D-aspartate receptors (NMDA-Rs) in the promnesiant effects of natural (+) pregnenolone sulfate (PREGS) and its synthetic (−) enantiomer ent-PREGS in young adult mice. Using the two-trial arm discrimination task in a Y-maze, PREGS and ent-PREGS administration to control mice increased memory performances. In mice with a knock-out of the NR1 subunit of NMDA-Rs in the forebrain, the promnesiant effect of ent-PREGS was maintained whereas the activity of PREGS was lost. Memory enhancement by PREGS involves the NMDA-R activity in the hippocampal CA1 area and possibly in some locations of the cortical layers, whereas ent-PREGS acts independently of NMDA-R function. PMID:21036556

  13. Synthetic pregnenolone derivatives as antiviral agents against acyclovir-resistant isolates of Herpes Simplex Virus Type 1.

    PubMed

    Dávola, María Eugenia; Mazaira, Gisela I; Galigniana, Mario D; Alché, Laura E; Ramírez, Javier A; Barquero, Andrea A

    2015-10-01

    The conventional therapy for the management of Herpes Simplex Virus Type 1 (HSV-1) infections mainly comprises acyclovir (ACV) and other nucleoside analogues. A common outcome of this treatment is the emergence of resistant viral strains, principally when immunosuppressed patients are involved. Thus, the development of new antiherpetic compounds remains as a central challenge. In this work we describe the synthesis and the in vitro antiherpetic activity of a new family of steroidal compounds derived from the endogenous hormone pregnenolone. Some of these derivatives showed a remarkable inhibitory effect on HSV-1 spread both on wild type and ACV-resistant strains. The results also show that these compounds seem to interfere with the late steps of the viral cycle. PMID:26259812

  14. Progesterone inhibits mast cell secretion.

    PubMed

    Vasiadi, M; Kempuraj, D; Boucher, W; Kalogeromitros, D; Theoharides, T C

    2006-01-01

    Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.

  15. Membrane progesterone receptors in reproduction and cancer.

    PubMed

    Valadez-Cosmes, Paulina; Vázquez-Martínez, Edgar Ricardo; Cerbón, Marco; Camacho-Arroyo, Ignacio

    2016-10-15

    Progesterone is a sexual steroid hormone that has a critical role in reproductive processes in males and females of several species, including humans. Furthermore, progesterone has been associated with pathological diseases such as breast, gynecological and brain cancer, regulating cell proliferation, apoptosis, and metastasis. In the past, progesterone actions were thought to be only mediated by its intracellular receptor (PR). However, recent evidence has demonstrated that membrane progesterone receptors (mPRs) mediate most of the non-classical progesterone actions. The role of the different mPRs subtypes in progesterone effects in reproduction and cancer is an emerging and exciting research area. Here we review studies to date regarding mPRs role in reproduction and cancer and discuss their functions and clinical relevance, suggesting mPRs as putative pharmacological targets and disease markers in cancer and diseases associated with reproduction. PMID:27368976

  16. Progesterone in normal and pathological pregnancy.

    PubMed

    Di Renzo, Gian Carlo; Giardina, Irene; Clerici, Graziano; Brillo, Eleonora; Gerli, Sandro

    2016-07-01

    Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. It has been proposed and extensively used in the treatment of different gynecological pathologies as well as in assisted reproductive technologies and in the maintenance of pregnancy. Called "the pregnancy hormone", natural progesterone is essential before pregnancy and has a crucial role in its maintenance based on different mechanisms such as: modulation of maternal immune response and suppression of inflammatory response (the presence of progesterone and its interaction with progesterone receptors at the decidua level appears to play a major role in the maternal defense strategy), reduction of uterine contractility (adequate progesterone concentrations in myometrium are able to counteract prostaglandin stimulatory activity as well as oxytocin), improvement of utero-placental circulation and luteal phase support (it has been demonstrated that progesterone may promote the invasion of extravillous trophoblasts to the decidua by inhibiting apoptosis of extravillous trophoblasts). Once the therapeutic need of progesterone is established, the key factor is the decision of the best route to administer the hormone and the optimal dosage determination. Progesterone can be administered by many different routes, but the most utilized are oral, the vaginal and intramuscular administration. The main uses of progesterone are represented by: threatened miscarriage, recurrent miscarriage and preterm birth (in the prevention strategy, as a tocolytic agent and also in the maintenance of uterine quiescence). PMID:27662646

  17. Altered levels of synapsin I, dopamine transporter, dynorphin A, and neuropeptide Y in the nucleus accumbens and striatum at post-puberty in rats treated neonatally with pregnenolone or DHEA.

    PubMed

    Muneoka, Katsumasa; Iwata, Masaaki; Shirayama, Yukihiko

    2009-10-01

    It is well documented that neonatal neurosteroid administration influences brain development. In our previous studies, administration of pregnenolone, the precursor of neurosteroids, during the neonatal period altered the activity of dopamine (DA) in the striatum. Furthermore, neonatal treatment with pregnenolone or dehydroepiandrosterone (DHEA) increased synapse-related protein synapsin I as well as neuropeptide Y (NPY) in the hippocampus. The present study examined the effects of neonatal treatment with pregnenolone or DHEA on synapsin I, DA transporter (DAT), dynorphin A, and NPY in the striatum and the core and shell of the nucleus accumbens at post-puberty. Administration of pregnenolone or DHEA during the neonatal period increased immunodensity of synapsin I in the dorsomedial or ventrolateral striatum. DAT immunodensity in the striatum and the nucleus accumbens core as well as dynorphin A immunodensity in the nucleus accumbens core were increased in DHEA-treated but not in pregnenolone-treated rats. In addition, the size, but not numbers, of NPY-positive cells in the nucleus accumbens core was increased in pregnenolone- and DHEA-treated rats. The results suggest that neurosteroid levels during the neonatal period have larger impact on synaptic formation, development of DA and NPY systems in the nigrostriatal rather than the mesolimbic pathway.

  18. [Progesterone and nitric oxide systems].

    PubMed

    Wieser, F; Gruber, D M; Tschugguel, W; Huber, J C

    1997-01-01

    Sexual steroids play an established role in the mechanisms concerning reproduction, ovulation, menstruation and onset of labour. However, sexual steroids are also involved in extragenital mechanisms, which were described for both oestrogen, and progesterone. Progesterone and its mechanisms of signal transduction still remain to be fully understood. However, there is evidence, that nitric oxide (NO) seems to be an important mediator in these mechanisms. NO, the molecule, which was described to exist in acid rain, was elected the molecule of the year 1992 from the American Academy of Science. NO is a short-lived molecule, which is involved in many reactions as an modulating transmitter due to its high diffusibility and its polarity. NO regulates the immune response of mononuclear cells, contractility of smooth muscle cells and neuronal transmission of non-adrenergic and non-cholinergic nerves. Additionally it was found, that NO may be important in the regulation of menstruation, the maintenance of uterine quiescence as well as the initiation of labour and the maturation of the uterine cervix.

  19. [Peroxidase activity of catalase modified by progesterone].

    PubMed

    Artemchik, V D; Matveentsev, V D; Metelitsa, D I

    1986-08-01

    Catalase conjugates with 3, 7, 9 and 42 progesterone molecules were obtained by the reaction between the enzyme and N-oxy-succinimide ether of 3-0-carboxymethyloxime of progesterone. The enzyme modified by 42 progesterone molecules is effective in o-dianisidine oxidation by hydrogen peroxide and has a kcat/KM value of 512 M-1 s-1. The catalase conjugates with 3, 7 and 9 progesterone molecules exhibit a high activity during o-dianisidine oxidation by cumene hydroperoxide. The activity of conjugates is higher than that of the native non-modified enzyme in the same reaction. The maximum effectiveness was observed for catalase modified by 7 progesterone molecules. This conjugate is characterized by kcat/KM of 99,000 M-1 s-1 at 30 degrees C. The effect of the degree of enzyme modification on the kinetic parameters of o-dianisidine oxidation by H2O2 and cumene hydroperoxide is discussed. PMID:3021241

  20. Progesterone

    MedlinePlus

    ... not had a hysterectomy (surgery to remove the uterus). Hormone replacement therapy usually includes estrogen, which is ... cause abnormal thickening of the lining of the uterus and increase the risk of developing uterine cancer. ...

  1. Intracellular redistribution of SCP2 in Leydig cells after hormonal stimulation may contribute to increased pregnenolone production.

    PubMed

    van Noort, M; Rommerts, F F; van Amerongen, A; Wirtz, K W

    1988-07-15

    Sterol carrier protein2 (SCP2) also designated non specific lipid transfer protein (nsL-TP), added to tumour Leydig cell mitochondria as a pure compound or in cytosolic preparations, stimulates pregnenolone production two- to three-fold. This stimulation can be abolished by addition of anti rat SCP2 but not by preimmune IgG-antibodies. SCP2- levels in the cytosol are increased in less than two minutes after addition of lutropin (LH). This increased SCP2 level may contribute to stimulation of steroid production in intact cells. After hormonal stimulation the subcellular distribution of SCP2 changes. A two-fold increase of SCP2- levels in the supernatant fraction and four-fold decrease in extracts of the particulate fraction was observed 30 min after stimulation of tumour Leydig cells with LH and subsequent fractionation. This apparent shift of SCP2 can be explained by an altered association with membranes or a true relocation of the protein from the particulate to the supernatant fractions under the influence of the hormone. PMID:3395346

  2. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    PubMed

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  3. Pregnenolone sulphate enhances spatial orientation and object discrimination in adult male rats: evidence from a behavioural and electrophysiological study.

    PubMed

    Plescia, Fulvio; Sardo, Pierangelo; Rizzo, Valerio; Cacace, Silvana; Marino, Rosa Anna Maria; Brancato, Anna; Ferraro, Giuseppe; Carletti, Fabio; Cannizzaro, Carla

    2014-01-01

    Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10mg/kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of both spatial orientation-acquisition and object discrimination in a simple and in a complex version of the visual task. Electrophysiological recordings were also performed in vivo, after acute PREGS systemic administration in order to investigate on the neuronal activation in the hippocampus and the perirhinal cortex. Our results indicate that, PREGS induces an improvement in spatial orientation-acquisition and in object discrimination in the simple and in the complex visual task; the behavioural responses were also confirmed by electrophysiological recordings showing a potentiation in the neuronal activity of the hippocampus and the perirhinal cortex. In conclusion, this study demonstrates that PREGS systemic administration in rats exerts cognitive enhancing properties which involve both the acquisition and utilization of spatial information, and object discrimination memory, and also correlates the behavioural potentiation observed to an increase in the neuronal firing of discrete cerebral areas critical for spatial learning and object recognition. This provides further evidence in support of the role of PREGS in exerting a protective and enhancing role on human memory.

  4. The Addition of A Pregnenolone Pendant Group Enhances the Anticancer Properties of Titanocene Dichloride in a MCF-7 Xenograft Model

    PubMed Central

    Ramos, Gladiany; Loperena, Yaliz; Ortiz, Giovanni; Reyes, Fiorella; Szeto, Ada; Vera, Jose; Velez, Javier; Morales, Jessica; Morrero, Deborah; Castillo, Linnette; Dharmawardhane, Surangani; Melendez, Enrique; Washington, A. Valance

    2014-01-01

    Background/Aim Titanocene dichloride held great promise as a chemotherapeutic compound in preclinical studies. However, subsequent clinical trials revealed hepatoxicity and nephrotoxicity, which limited its use in clinical applications. Therefore, we used steroid pendant groups to improve the targeting of titanocene in the MCF-7 breast cancer cell line, and demonstrated a 10-fold lower effective dose compared to titanocene in in vitro assays. The aim of the present study was to test the efficacy of a titanocene functionalized with pregnenolone (Ti-Preg) in an in vivo breast cancer model. Materials and Methods Xenografts from the MCF7 breast cancer cell line were implanted into athymic nu/nu mice to evaluate the potential of Ti-Preg as an anti-breast cancer agent. Results Ti-Preg demonstrated a significant inhibition of MCF-7 tumor growth when compared to vehicle and to titanocene controls. Conclusion Our findings demonstrate the potential of steroid pendent groups for targeting chemotherapeutics to steroid hormone-dependent cancer. PMID:24692689

  5. Studies on neurosteroids XV. Development of enzyme-linked immunosorbent assay for examining whether pregnenolone sulfate is a veritable neurosteroid.

    PubMed

    Higashi, Tatsuya; Daifu, Yuri; Ikeshima, Takehiro; Yagi, Takako; Shimada, Kazutake

    2003-01-15

    An enzyme-linked immunosorbent assay (ELISA) of pregnenolone sulfate (PREGS) has been developed for examining whether it is a veritable neurosteroid. 11alpha-Hemiglutaryloxy-PREGS was newly synthesized and conjugated with bovine serum albumin (BSA), which was injected to rabbits for the production of anti-PREGS antibodies. A bridge-heterologous ELISA system employing the sequential saturation method exhibited a high sensitivity with a midpoint of 30 pg. Although the antibody showed some cross-reactivity with PREG (4.4%), it easily discriminated other related steroids reported to exist in the mammalian brain. The rat brain homogenate was treated with hexane and subjected to an OASIS HLB cartridge, which was washed with AcOEt to remove the unconjugated steroids, and then the desired sulfate was eluted with EtOH. The recovery rate of PREGS through the pretreatment was satisfactory, but its brain levels in the preliminary experiments were much lower than those previously measured by gas chromatography (GC)-mass spectrometry (MS) after solvolysis. These results practically agreed with our previous results by liquid chromatography (LC)-electrospray ionization (ESI)-MS without deconjugation.

  6. The role of pregnenolone sulphate in spatial orientation-acquisition and retention: an interplay between cognitive potentiation and mood regulation.

    PubMed

    Plescia, Fulvio; Marino, Rosa A M; Cannizzaro, Emanuele; Brancato, Anna; Cannizzaro, Carla

    2013-10-01

    Neurosteroids can alter neuronal excitability interacting with specific neurotransmitter receptors, thus affecting several functions such as cognition and emotionality. In this study, we investigated, in adult male rats, the effects of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s.c.) on cognitive processes using the Can test, a non aversive spatial/visual task which allows the assessment of spatial information-acquisition during the baseline training, and of memory retention in the longitudinal study. Furthermore, on the basis of PREGS pharmacological profile, the modulation of depressive-like behaviour was also evaluated in the forced swim test (FST). Our results indicate that acute PREGS induces: an improvement in spatial orientation-acquisition and in reference memory, during the baseline training; a strengthening effect on reference and working memory during the longitudinal study. A decrease in immobility time in the FST has also been recorded. In conclusion, PREGS exerts enhancing properties on acquisition, consolidation and retrieval of spatial information, probably due of improved hippocampal-dependent memory processes. The additional antidepressant effect observed in the FST can provide further evidence in support of the potential of PREGS as a therapeutic tool for the treatment of cognitive deficits associated with mood disorders. This article is part of a Special Issue entitled: insert SI title.

  7. Progesterone Receptors: Form and Function in Brain

    PubMed Central

    Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

    2008-01-01

    Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

  8. Progesterone in Peri- and Postmenopause: A Review

    PubMed Central

    Regidor, P.-A.

    2014-01-01

    Around 14.5 million peri- and postmenopausal women currently live in Germany. Moreover, approximately 450 000 women, each with a life expectancy of around 85 years, reach menopause every year in Germany. The challenge is therefore to find a therapy with few side effects which could improve the quality of life of women with menopausal symptoms. The aim of hormone therapy (HT) is to remedy hormone deficiencies using substances that offer the best trade-off between benefits and risks. This is where progesterone has a new and important role to play. Progesterone is one of the most important gestagens. Biologically effective progesterone formulations created with micronization techniques have been used in clinical practice since 1996. Nevertheless, up until 2003 preference was given to synthetic gestagens rather than progesterone. The increased breast cancer hazard ratio of 1.23 reported in the WHI study and of 2 given in the Million Women Study has been associated with the use of synthetic gestagens. In a comparison between synthetic gestagens and progesterone, the E3N Study showed that the transdermal administration of estrogen and progesterone did not lead to an increase in breast cancer rates (RR: 1.08). The administration of progesterone does not change the HDL/LDL cholesterol ratio. Because of its anti-mineralocorticoid effect, progesterone has no impact on carbohydrate metabolism, hemostasis, blood pressure, thrombogenicity and body weight. The administration of 200 mg/day progesterone over 12 days of a menstrual cycle or a daily administration of 100 mg combined with an estrogen are a safe and well-tolerated option to treat menopausal symptoms, with a better benefit risk profile compared to synthetic gestagens. PMID:25484373

  9. Progesterone in Peri- and Postmenopause: A Review.

    PubMed

    Regidor, P-A

    2014-11-01

    Around 14.5 million peri- and postmenopausal women currently live in Germany. Moreover, approximately 450 000 women, each with a life expectancy of around 85 years, reach menopause every year in Germany. The challenge is therefore to find a therapy with few side effects which could improve the quality of life of women with menopausal symptoms. The aim of hormone therapy (HT) is to remedy hormone deficiencies using substances that offer the best trade-off between benefits and risks. This is where progesterone has a new and important role to play. Progesterone is one of the most important gestagens. Biologically effective progesterone formulations created with micronization techniques have been used in clinical practice since 1996. Nevertheless, up until 2003 preference was given to synthetic gestagens rather than progesterone. The increased breast cancer hazard ratio of 1.23 reported in the WHI study and of 2 given in the Million Women Study has been associated with the use of synthetic gestagens. In a comparison between synthetic gestagens and progesterone, the E3N Study showed that the transdermal administration of estrogen and progesterone did not lead to an increase in breast cancer rates (RR: 1.08). The administration of progesterone does not change the HDL/LDL cholesterol ratio. Because of its anti-mineralocorticoid effect, progesterone has no impact on carbohydrate metabolism, hemostasis, blood pressure, thrombogenicity and body weight. The administration of 200 mg/day progesterone over 12 days of a menstrual cycle or a daily administration of 100 mg combined with an estrogen are a safe and well-tolerated option to treat menopausal symptoms, with a better benefit risk profile compared to synthetic gestagens. PMID:25484373

  10. Overview of progesterone profiles in dairy cows.

    PubMed

    Blavy, P; Derks, M; Martin, O; Höglund, J K; Friggens, N C

    2016-09-01

    The aim of this study was to gain a better understanding of the variability in shape and features of all progesterone profiles during estrus cycles in cows and to create templates for cycle shapes and features as a base for further research. Milk progesterone data from 1418 estrus cycles, coming from 1009 lactations, was obtained from the Danish Cattle Research Centre in Foulum, Denmark. Milk samples were analyzed daily using a Ridgeway ELISA-kit. Estrus cycles with less than 10 data points or shorter than 4 days were discarded, after which 1006 cycles remained in the analysis. A median kernel of three data points was used to smooth the progesterone time series. The time between start of progesterone rise and end of progesterone decline was identified by fitting a simple model consisting of base length and a quadratic curve to progesterone data, and this luteal-like phase (LLP) was used for further analysis. The data set of 1006 LLP's was divided into five quantiles based on length. Within quantiles, a cluster analysis was performed on the basis of shape distance. Height, upward and downward slope, and progesterone level on Day 5 were compared between quantiles. Also, the ratio of typical versus atypical shapes was described, using a reference curve on the basis of data in Q1-Q4. The main results of this article were that (1) most of the progesterone profiles showed a typical profile, including the ones that exceeded the optimum cycle length of 24 days; (2) cycles in Q2 and Q3 had steeper slopes and higher peak progesterone levels than cycles in Q1 and Q4 but, when normalized, had a similar shape. Results were used to define differences between quantiles that can be used as templates. Compared to Q1, LLP's in Q2 had a shape that is 1.068 times steeper and 1.048 times higher. Luteal-like phases in Q3 were 1.053 times steeper and 1.018 times higher. Luteal-like phases in Q4 were 0.977 times steeper and 0.973 times higher than LLP's in Q1. This article adds to our

  11. [Progesterone transport across the wall of the rumen of sheep].

    PubMed

    Borisenkov, M F; Vaĭkishnoraĭte, M A; Kaneva, A M

    2003-09-01

    Data on content of fiber, lignin and progesterone in reticulo-ruminal chyme and progesterone in blood serum and saliva of sheep throughout the reproductive cycle and at intramuscular injection of progesterone, are presented. A direct correlation between concentration of progesterone in blood and chyme was revealed. 1.5% of progesterone entered the reticulo-rumen with saliva. Transport of hormone through the wall of forestomach is the main way of progesterone entering the reticulo-rumen. The transport is carried out against the gradient of hormone concentration. Possible participation of progesterone adsorption on lignin in explanation of this transport, is discussed.

  12. Promotion of thyroid tumors in rats by pregnenolone-16alpha-carbonitrile (PCN) and polychlorinated biphenyl (PCB).

    PubMed

    Vansell, Nichole R; Muppidi, Jagan R; Habeebu, Sultan M; Klaassen, Curtis D

    2004-09-01

    Pregnenolone-16alpha-carbonitrile (PCN) and Aroclor 1254 (PCB) both reduce serum thyroid hormone levels in rats, but only PCN consistently produces an increase in serum thyrotropin (TSH). PCN-mediated increases in TSH result in increased thyroid follicular cell proliferation and hyperplasia, which may represent early events on a morphological continuum leading to neoplasia. The purpose of this study was to assess whether PCN, a compound that increases serum TSH, and PCB, which does not increase TSH, promote thyroid tumors in a two-stage carcinogenesis model. Male SD rats were administered the thyroid tumor initiator diisopropanolnitrosamine (2.5 g/kg, sc), and after seven days were fed control diet, diet containing 1000 ppm PCN, or diet containing 100 ppm PCB for 19 weeks. Body weights were unaffected by PCN treatment, but were reduced 21% after 19 weeks of PCB treatment compared to control. PCN treatment significantly reduced serum T4 through week 3 before returning to control concentrations, whereas T4 levels following PCB treatment fell below detection limits by week 3 and remained drastically reduced through week 19. TSH concentrations in PCN-treated rats increased three-fold at week 2, then declined to near control values at week 19. After one week of PCB treatment, TSH concentrations reached nearly twice that of controls, and were sustained until week 6. The incidence of thyroid follicular cell proliferative lesions, including cystic and follicular hyperplasia, cystic and follicular adenoma, and follicular carcinoma, was significantly increased following PCN treatment, but not following PCB treatment. PCB treatment caused an increase in thyroid carcinomas (4 of 22 rats) not associated with the proliferative-type lesions produced by PCN, despite an increase in TSH serum concentrations. In conclusion, PCN appears to promote thyroid tumors in a manner consistent with known effects of excessive TSH stimulation. However, thyroid carcinomas stemming from PCB

  13. Induction of UDP-glucuronosyltransferase activities in Gunn, heterozygous, and Wistar rat livers by pregnenolone-16 alpha-carbonitrile.

    PubMed

    Watkins, J B; Klaassen, C D

    1982-01-01

    The effect of pregnenolone-16 alpha-carbonitrile (PCN) on UDP-glucuronosyltransferase (UDP-GT) activity was comprehensively examined in Wistar (JJ), heterozygous (Jj) and Gunn (jj) rats with eleven different acceptors for glucuronic acid. UDP-GT activity after 3-methylcholanthrene (3-MC) and phenobarbital (PB) treatment was studied in additional rats for comparative purposes. Conjugation of group-1 aglycones (1-naphthol and p-nitrophenol) was much lower in Gunn than in Wistar rats. PCN did not alter UDP-GT conjugation of these acceptors. UDP-GT activity toward group-1 aglycones was increased by 3-MC in Wistar and heterozygous rats but was not enhanced in Gunn rats by any inducer. Activity toward group-2 aglycones (morphine, chloramphenicol, valproic acid) was similar in control rats of all genotypes. PCN increased chloramphenicol conjugation, whereas PB enhanced the glucuronidation of all group-2 aglycones in Wistar, heterozygous, and Gunn rats. Conjugation of group-3 acceptors (bilirubin and digitoxigenin monodigitoxoside, DIG) was deficient in Gunn rats and was not inducible. PCN increased glucuronidation of bilirubin and DIG in Wistar and heterozygous rats. The concentration of UDP-glucuronic acid (UDPGA) in liver was similar in control animals of all genotypes and was increased in rats treated with 3-MC. The other inducers did not affect hepatic UDPGA levels. Thus, 3-MC, PB, and PCN induce UDP-GT activities toward different groups of acceptors of glucuronic acid. The results support the hypothesis that PCN induces a form of UDP-GT that preferentially conjugates the group-3 acceptors, bilirubin and DIG.

  14. Progesterone exerts neuroprotective effects after brain injury.

    PubMed

    Stein, Donald G

    2008-03-01

    Progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. This review assesses recent, primarily in vivo, evidence that progesterone can play an important role in promoting and enhancing repair after traumatic brain injury and stroke. Although many of its specific actions on neuroplasticity remain to be discovered, there is growing evidence that this hormone may be a safe and effective treatment for traumatic brain injury and other neural disorders in humans.

  15. Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

    PubMed

    Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

    2015-12-15

    Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone.

  16. Therapeutic effects of progesterone in animal models of neurological disorders.

    PubMed

    De Nicola, Alejandro F; Coronel, Florencia; Garay, Laura I; Gargiulo-Monachelli, Gisella; Gonzalez Deniselle, Maria Claudia; Gonzalez, Susana L; Labombarda, Florencia; Meyer, Maria; Guennoun, Rachida; Schumacher, Michael

    2013-12-01

    Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone receptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites with neurotransmitter receptors. We next described our results involving animal models of human neuropathologies to elucidate the protective roles of progesterone. We described: (a) the protective and promyelinating effects of progesterone in experimental spinal cord injury; (b) the progesterone protective effects exerted upon motoneurons in the degenerating spinal cord of Wobbler mouse model of amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects of progesterone in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis and after lysolecithin demyelination; (d) the progesterone prevention of nociception and neuropathic pain which follow spinal cord injury; and (e) the protective effect of progesterone in experimental ischemic stroke. Whenever available, the molecular mechanisms involved in these progesterone effects were examined. The multiplicity of progesterone beneficial effects has opened new venues of research for neurological disorders. In this way, results obtained in animal models could provide the basis for novel therapeutic strategies and pre-clinical studies.

  17. Binding of ATP to the progesterone receptor.

    PubMed Central

    Moudgil, V K; Toft, D O

    1975-01-01

    The possible interaction of progesterone--receptor complexes with nucleotides was tested by affinity chromatography. The cytosol progesterone receptor from hen oviduct was partially purified by ammonium sulfate precipitation before use. When progesterone was bound to the receptor, the resulting complex could be selectively adsorbed onto columns of ATP-Sepharose. This interaction was reversible and of an ionic nature since it could be disrupted by high-salt conditions. A competitive binding assay was used to test the specificity of receptor binding to several other nucleotides, including ADP, AMP, and cAMP. A clear specificity for binding ATP was evident from these studies. When ATP was added to receptor preparations, the nucleotide did not affect the sedimentation properties or hormone binding characteristics of the receptor. Although the function of ATP remains unknown, these studies indicate a role of this nucleotide in some aspect of hormone receptor activity. PMID:165493

  18. Progesterone receptor expression declines in the guinea pig uterus during functional progesterone withdrawal and in response to prostaglandins.

    PubMed

    Welsh, Toni N; Hirst, Jonathan J; Palliser, Hannah; Zakar, Tamas

    2014-01-01

    Progesterone withdrawal is essential for parturition, but the mechanism of this pivotal hormonal change is unclear in women and other mammals that give birth without a pre-labor drop in maternal progesterone levels. One possibility suggested by uterine tissue analyses and cell culture models is that progesterone receptor levels change at term decreasing the progesterone responsiveness of the myometrium, which causes progesterone withdrawal at the functional level and results in estrogen dominance enhancing uterine contractility. In this investigation we have explored whether receptor mediated functional progesterone withdrawal occurs during late pregnancy and labor in vivo. We have also determined whether prostaglandins that induce labor cause functional progesterone withdrawal by altering myometrial progesterone receptor expression. Pregnant guinea pigs were used, since this animal loses progesterone responsiveness at term and gives birth in the presence of high maternal progesterone level similarly to primates. We found that progesterone receptor mRNA and protein A and B expression decreased in the guinea pig uterus during the last third of gestation and in labor. Prostaglandin administration reduced while prostaglandin synthesis inhibitor treatment increased progesterone receptor A protein abundance. Estrogen receptor-1 protein levels remained unchanged during late gestation, in labor and after prostaglandin or prostaglandin synthesis inhibitor administration. Steroid receptor levels were higher in the non-pregnant than in the pregnant uterine horns. We conclude that the decreasing expression of both progesterone receptors A and B is a physiological mechanism of functional progesterone withdrawal in the guinea pig during late pregnancy and in labor. Further, prostaglandins administered exogenously or produced endogenously stimulate labor in part by suppressing uterine progesterone receptor A expression, which may cause functional progesterone withdrawal, promote

  19. Progesterone to prevent spontaneous preterm birth

    PubMed Central

    Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

    2014-01-01

    Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth <33 weeks of gestation, 12 patients with a short cervix would need to be treated. Vaginal progesterone reduces the rate of spontaneous preterm birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

  20. Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility.

    PubMed

    Beckley, Ethan H; Finn, Deborah A

    2007-10-01

    Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5alpha-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p<.05). In another experiment, 3 days of PWD significantly decreased levels of progesterone compared to 0 days of withdrawal, but progesterone levels at 3 days of PWD did not differ from vehicle-treated controls. In a final study, mice received daily injections of progesterone (5 mg/kg IP) for 8 days, with 0 mg/kg, 50 mg/kg, or 100 mg/kg finasteride co-administered for the last three days. Mice that received 100 mg/kg finasteride, but not 50 mg/kg finasteride, displayed increased FST immobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.

  1. Altrenogest and progesterone therapy during pregnancy in bottlenose dolphins (Tursiops truncatus) with progesterone insufficiency.

    PubMed

    Robeck, Todd R; Gill, Claudia; Doescher, Bethany M; Sweeney, Jay; De Laender, Piet; Van Elk, Cornelis E; O'Brien, Justine K

    2012-06-01

    Progesterone production is essential for growth and development of the conceptus during pregnancy. Abnormal development of the corpus luteum (CL) after conception can result in early embryonic loss or fetal abortion. Routine monitoring of bottlenose dolphin (Tursiops truncatus) pregnancy after artificial insemination or natural conception with ultrasonography and serum progesterone determination has allowed for the establishment of expected fetal growth rates and hormone concentrations. Using these monitoring techniques, we revealed four pregnant dolphins (12-24 yr old) with abnormally low progesterone production indicative of luteal insufficiency. Once diagnosed, animals were placed on altrenogest (0.044-0.088 mg/kg once daily) alone or with oral progesterone (50-200 mg twice daily). Doses of hormone were increased or decreased in each animal based on how fetal skull biparietal and thoracic growth rates compared with published normal values. Hormones were withdrawn starting from day 358 of gestation in animals 1 and 2, with labor occurring 6 and 7 days after withdrawal and at 376 and 373 days of gestation, respectively. Both deliveries were dystocic, with each calf requiring manual extraction and fetotomy for calf 1. The fetuses in animals 3 and 4 died at 348 and 390 days of gestation, respectively. Induction of labor was attempted in both animals, after fetal death, by using a combination of rapid progesterone withdrawal and steroid and prostaglandin F2alpha administration. The calf of animal 4 had to be removed with manual cervical dilation and fetotomy All adult females survived the procedures. These data provide the first in vivo evidence that the CL is the primary source of progesterone throughout pregnancy in the bottlenose dolphin. Until further characterization of hormones required during pregnancy and at parturition has been accomplished, the exogenous progestagen supplementation protocol described here cannot be recommended for treatment of progesterone

  2. Milk progesterone for pregnancy diagnosis in dairy goats.

    PubMed

    Pennington, J A; Hoffman, W F; Schultz, L H; Spahr, S L; Lodge, J R

    1982-10-01

    Factors affecting progesterone concentration in milk of lactating dairy goats and use of this milk for pregnancy diagnosis were studied. Radioimmunoassay was used to assay progesterone in milk. Mean milk progesterone (ng/ml) +/- standard errors of 6 pregnant does for first, composite, and last milk were 9.9 +/- 2.0, 18.2 +/- 3.5, and 21.7 +/- 4.1. Correlation between milk fat and progesterone in composite milk was low (.11). Composite milk samples from 4 nonpregnant does were obtained daily throughout the estrous cycle. Milk progesterone (ng/ml) was 1 to 2 at estrus, rose to 5 to 12 within 2 to 5 days, reached a plateau at 15 to 25 in the middle of the estrous cycle, and then dropped to low concentrations again at 3 to 5 days before the next estrus. Milk progesterone also was used to diagnose pregnancy in 72 does. Forty-two does were diagnosed pregnant by high progesterone; 36 of these does later produced kids, and 5 other does aborted in various stages of pregnancy. Of 21 does diagnosed not pregnant with low progesterone, 19 does were not pregnant by either return to estrus or lack of parturition in the spring. All three incorrectly diagnosed does were problem breeders. Nine does with intermediate milk progesterone were classified questionable. Milk progesterone can be used to provide an early indication of the pregnancy status of does. PMID:7174966

  3. Structure of the human progesterone receptor gene.

    PubMed

    Misrahi, M; Venencie, P Y; Saugier-Veber, P; Sar, S; Dessen, P; Milgrom, E

    1993-11-16

    The complete organization of the human progesterone receptor (hPR) gene has been determined. It spans over 90 kbp and contains eight exons. The first exon encodes the N-terminal part of the receptor. The DNA binding domain is encoded by two exons, each exon corresponding to one zinc finger. The steroid binding domain is encoded by five exons. The nucleotide sequence of 1144 bp of the 5' flanking region has been determined. PMID:8241270

  4. Rethinking progesterone regulation of female reproductive cyclicity

    PubMed Central

    Kubota, Kaiyu; Cui, Wei; Dhakal, Pramod; Wolfe, Michael W.; Rumi, M. A. Karim; Vivian, Jay L.; Roby, Katherine F.; Soares, Michael J.

    2016-01-01

    The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null mutation at the Pgr locus has forced a reexamination of the role of progesterone in the regulation of the female reproductive cycle. We generated two Pgr mutant rat models, using genome editing. In both cases, deletions yielded a null mutation resulting from a nonsense frame-shift and the emergence of a stop codon. Similar to Pgr null mice, Pgr null rats were infertile because of deficits in sexual behavior, ovulation, and uterine endometrial differentiation. However, in contrast to the reported phenotype of female mice with disruptions in Pgr signaling, Pgr null female rats exhibit robust estrous cycles. Cyclic changes in vaginal cytology, uterine histology, serum hormone levels, and wheel running activity were evident in Pgr null female rats, similar to wild-type controls. Furthermore, exogenous progesterone treatment inhibited estrous cycles in wild-type female rats but not in Pgr-null female rats. As previously reported, pharmacologic antagonism supports a role for PGR signaling in the regulation of the ovulatory gonadotropin surge, a result at variance with experimentation using genetic ablation of PGR signaling. To conclude, our findings in the Pgr null rat challenge current assumptions and prompt a reevaluation of the hormonal control of reproductive cyclicity. PMID:27035990

  5. Progesterone Receptor Action in Leiomyoma and Endometrial Cancer

    PubMed Central

    Kim, J. Julie; Sefton, Elizabeth C.; Bulun, Serdar E.

    2013-01-01

    Progesterone is a key hormone in the regulation of uterine function. In the normal physiological context, progesterone is primarily involved in remodeling of the endometrium and maintaining a quiescent myometrium. When pathologies of the uterus develop, specifically, endometrial cancer and uterine leiomyoma, response to progesterone is usually altered. Progesterone acts through mainly two isoforms of the progesterone receptor (PR), PRA and PRB which have been reported to exhibit different transcriptional activities. Studies examining the expression and function of the PRs in the normal endometrium and myometrium as well as in endometrial cancer and uterine leiomyoma are summarized here. The clinical use of progestins and the transcriptional activity of the PR on genes specific to endometrial cancer and leiomyoma are described. An increased understanding of the differential expression of PRs and response to progesterone in these two diseases is critical in order to develop more efficient and targeted therapies. PMID:20374701

  6. [Reproductive physiology of the European mink: progesterone profile during pregnancy].

    PubMed

    Amstislavskiĭ, S Ia; Zav'ialov, E L; Ternovskaia, Iu G; Gerlinskaia, L A

    2010-04-01

    Reproductive physiology of the European mink, an endangered mustelid species, has been so far scarcely investigated. This study confirms that in European mink embryo implantation occurs on the day 12 of pregnancy. Progesterone profile during pregnancy has been compared in European mink and domestic ferret. In both species, progesterone increases at peri-implantation period, i. e. on day 8 and day 12 after mating. However, toward the end of pregnancy, on day 40 after mating, progesterone concentration in faeces of the ferrets decreases and does not differ from the initial level. In contrast, increase of progesterone during first 12 days of pregnancy in European mink is not as rapid as in ferrets, but in this species, there is no visible decrease of progesterone at the end of pregnancy. Peak levels of progesterone in faeces (day 8, 12) are lower in European mink than in ferret.

  7. Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

    PubMed Central

    Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

    2016-01-01

    Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID

  8. Expression of rat Multidrug Resistance Protein 2 (Mrp2) in male and female rats during normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny.

    PubMed

    Johnson, David R; Guo, Grace L; Klaassen, Curtis D

    2002-09-16

    The normal maturation of biliary organic anion excretion in newborn rats can be enhanced by microsomal enzyme-inducing chemical treatment, yet the mechanism for this phenomenon is not known. Multidrug Resistance Protein 2 (Mrp2) is a biliary efflux transporter that is inducible by select microsomal enzyme-inducing chemicals. Thus, the aims of this study were to compare the normal and pregnenolone-16alpha-carbonitrile (PCN)-induced postnatal ontogeny of Mrp2 in male and female rats. Mrp2 protein increased in an age-dependent manner in both sexes between 0 and 90 days of age. At birth, Mrp2 protein in both male and female rats was the same, approximately 70% of adult levels. Mrp2 protein in both sexes reached maximal expression levels that were higher than adult levels (male: days 25-40; female: day 45), then decreased to adult levels, at which age Mrp2 protein expression in male and female rats was the same. Second, male and female rats of various ages were treated with PCN (75 mg/kg, ip) or corn oil for 4 days, after which livers were removed and analyzed for Mrp2 protein and mRNA expression. PCN accelerated the expression of Mrp2 protein in male and female rats as early as 10 days of age, whereas, PCN did not affect male and female Mrp2 mRNA ontogeny. These data suggest that PCN increased Mrp2 protein by a sex-independent posttranscriptional mechanism.

  9. Control of parturition in the sow using progesterone and prostaglandin.

    PubMed

    Gooneratne, A; Hartmann, P E; McCauley, I; Martin, C E

    1979-12-01

    The effect of progesterone and prostaglandin administration on the timing of farrowing was studied in three groups of 25 sows each. Progesterone treatment (100 mg/day) on days 112, 113 and 114 of gestation (group I) significantly prolonged the gestation length to 116.4 +/- 0.4 (mean +/- s.e.) days compared to the control sows (group III; 115.5 +/- 0.2; P less than 0.05). Administration of prostaglandin (200 micrograms Cloprostanol intramuscularly) on day 115 of gestation following progesterone treatment (group II) resulted in a gestation length of 116.0 +/- 0.1 days, with the sows farrowing 25.4 +/- 1.0 h after the prostaglandin injection. 80% of the sows farrowed between 0800 and 1700 h of day 116 of gestation. Plasma progesterone levels were maintained by the exogenous progesterone during treatment. At farrowing, higher levels of progesterone were observed in groups I and II compared to controls. Prostaglandin treatment did not significantly alter withdrawal of progesterone in progesterone treated sows, suggesting that the actions of exogenous prostaglandin is primarily on the myometrium and the cervix. Hormonal treatment in late pregnancy did not have any adverse effects on piglet viability and growth rate, or subsequent reproductive performances of sows. Lactation was initiated normally, and the concentrations of lactose, protein, fat, IgG, Na+, Ca2+ and K+ in colostrum and milk were similar in all groups during the first 5 days of lactation.

  10. Ventilatory response of rabbits and goats to chronic progesterone administration.

    PubMed

    Smith, C A; Kellogg, R H

    1980-03-01

    We assessed the ventilatory response to chronic progesterone administration of 37 male rabbits and 4 castrated male goats. Rabbits, in response to 2.72 mg.kg-1.day-1 of progesterone, did not chronically hyperventilate as measured by changes in CSF [HCO-3]. Two goats given 10 mg/kg/day of progesterone by intramuscular injection, alone or in combination with estradiol or testosterone, manifested no convincing ventilatory changes. Two goats were given progesterone in the form of progesterone-containing Silastic implants. Serum progesterone levels of 8-27 ng/ml were maintained over the course of 45 days. The hyperventilation in these goats, unlike that of man, was slow to develop (8-15 days), slow to decay (10-30 days), and relatively small (resting PETCO2 fell 3-5 mm Hg relative to control); and there was no change in slope of the CO2 response curves. We conclude that goats and rabbits do not respond to progesterone like man, and therefore are not good models with which to study the mechanism(s) by which progesterone produces hyperventilation in man. PMID:7384660

  11. Protective Effect of Progesterone during Pregnancy against Ovarian Cancer

    PubMed Central

    Han, Kyung Hee; Kim, Mi-Kyung; Kim, Hee Seung; Chung, Hyun Hoon; Song, Yong Sang

    2013-01-01

    There have been several epidemiologic studies supporting the protective role of pregnancy, although the mechanism is not clear. High level of progesterone, which is crucial in maintaining pregnancy, has been supposed to be one of the causative factors. Progesterone is produced at the corpus luteum in the early pregnancy and the placenta in the late pregnancy period. In several experimental studies, progesterone was reported to induce apoptosis of ovarian cancer cells through intrinsic and extrinsic pathways. In addition, progesterone has been shown to exert its anticancer effect through genomic and non-genomic action. The objective of this review is to discuss the protective mechanism of pregnancy against ovarian cancer focusing on the steroid hormone, progesterone. PMID:25337537

  12. Persistent genital hyperinnervation following progesterone administration to adolescent female rats.

    PubMed

    Liao, Zhaohui; Smith, Peter G

    2014-12-01

    Provoked vestibulodynia, a female pelvic pain syndrome affecting substantial numbers of women, is characterized by genital hypersensitivity and sensory hyperinnervation. Previous studies have shown that the risk of developing provoked vestibulodynia is markedly elevated following adolescent use of oral contraceptives with high progesterone content. We hypothesized that progesterone, a steroid hormone with known neurotropic properties, may alter genital innervation through direct or indirect actions. Female Sprague Dawley rats received progesterone (20 mg/kg subcutaneously) from Days 20-27; tissue was removed for analysis in some rats on Day 28, while others were ovariectomized on Day 43 and infused for 7 days with vehicle or 17beta estradiol. Progesterone resulted in overall increases in vaginal innervation at both Day 28 and 50 due to proliferation of peptidergic sensory and sympathetic (but not parasympathetic) axons. Estradiol reduced innervation in progesterone-treated and untreated groups. To assess the mechanisms of sensory hyperinnervation, we cultured dissociated dorsal root ganglion neurons and found that progesterone increases neurite outgrowth by small unmyelinated (but not myelinated) sensory neurons, it was receptor mediated, and it was nonadditive with NGF. Pretreatment of ganglion with progesterone also increased neurite outgrowth in response to vaginal target explants. However, pretreatment of vaginal target with progesterone did not improve outgrowth. We conclude that adolescent progesterone exposure may contribute to provoked vestibulodynia by eliciting persistent genital hyperinnervation via a direct effect on unmyelinated sensory nociceptor neurons and that estradiol, a well-documented therapeutic, may alleviate symptoms in part by reducing progesterone-induced sensory hyperinnervation. PMID:25359899

  13. Progesterone neuroprotection in traumatic CNS injury and motoneuron degeneration.

    PubMed

    De Nicola, Alejandro F; Labombarda, Florencia; Gonzalez Deniselle, Maria Claudia; Gonzalez, Susana L; Garay, Laura; Meyer, Maria; Gargiulo, Gisella; Guennoun, Rachida; Schumacher, Michael

    2009-07-01

    Studies on the neuroprotective and promyelinating effects of progesterone in the nervous system are of great interest due to their potential clinical connotations. In peripheral neuropathies, progesterone and reduced derivatives promote remyelination, axonal regeneration and the recovery of function. In traumatic brain injury (TBI), progesterone has the ability to reduce edema and inflammatory cytokines, prevent neuronal loss and improve functional outcomes. Clinical trials have shown that short-and long-term progesterone treatment induces a significant improvement in the level of disability among patients with brain injury. In experimental spinal cord injury (SCI), molecular markers of functional motoneurons become impaired, including brain-derived neurotrophic factor (BDNF) mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and choline acetyltransferase (ChAT). SCI also produces motoneuron chromatolysis. Progesterone treatment restores the expression of these molecules while chromatolysis subsided. SCI also causes oligodendrocyte loss and demyelination. In this case, a short progesterone treatment enhances proliferation and differentiation of oligodendrocyte progenitors into mature myelin-producing cells, whereas prolonged treatment increases a transcription factor (Olig1) needed to repair injury-induced demyelination. Progesterone neuroprotection has also been shown in motoneuron neurodegeneration. In Wobbler mice spinal cord, progesterone reverses the impaired expression of BDNF, ChAT and Na,K-ATPase, prevents vacuolar motoneuron degeneration and the development of mitochondrial abnormalities, while functionally increases muscle strength and the survival of Wobbler mice. Multiple mechanisms contribute to these progesterone effects, and the role played by classical nuclear receptors, extra nuclear receptors, membrane receptors, and the reduced metabolites of progesterone in neuroprotection and myelin formation remain an exciting field worth of exploration

  14. Progesterone action in breast, uterine, and ovarian cancers

    PubMed Central

    Diep, Caroline H.; Daniel, Andrea R.; Mauro, Laura J.; Knutson, Todd P.; Lange, Carol A.

    2015-01-01

    Progesterone and progesterone receptors (PR) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two progesterone receptor isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential cross-talk with growth factor signaling pathways, and distinct post-translational modifications and cofactor binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases. PMID:25587053

  15. Progesterone and mental rotation task: is there any effect?

    PubMed

    Noreika, Donatas; Griškova-Bulanova, Inga; Alaburda, Aidas; Baranauskas, Mindaugas; Grikšienė, Ramunė

    2014-01-01

    Mental rotation task (MRT) incorporates elements of spatial abilities, important in many professions, with people of both genders involved. Importantly, these are the areas where spatial tasks might be performed for long time periods; thus adverse effects of mental fatigue are highly unwanted. Substantial variation of MRT performance in relation to estrogen levels has been observed in many studies, whereas the role of progesterone remains elusive. Here we aimed to elucidate the effect of progesterone level on the long-duration (1.5 hours) performance of MRT. We included three groups of subjects: a group of males as a control, a group of females in their follicular phase (low progesterone) and a group of females in their luteal phase (high progesterone), MRT accuracy and response time, subjective fatigue ratings and cardiovascular measures together with 17 β -estradiol and progesterone concentrations were analyzed. We found that subjective ratings of fatigue increased, performance accuracy increased, and mean response times decreased during the task in all groups. Females in luteal phase were significantly slower not only than men, but also than females in their follicular phase. An increase in subjective fatigue ratings was positively related to progesterone level-at higher progesterone levels, females felt more tired. PMID:24818150

  16. [Intracellular traffic of the progesterone receptor].

    PubMed

    Guiochon-Mantel, A; Lescop, P; Christin-Maitre, S; Perrot-Applanat, M; Milgrom, E

    1992-01-01

    The nuclear localization of the progesterone receptor is mediated by two signal sequences: one is constitutive and lies in the hinge region (between the DNA and steroid binding domains), the other is hormone-dependent and is localized in the second zinc finger of the DNA binding domain. The use of various inhibitors of energy synthesis in cells expressing permanently or transiently the wild-type receptor or a receptor mutated within the nuclear localization signals, demonstrated that the nuclear residency of the receptor reflects a dynamic situation: the receptor diffusing into the cytoplasm and being constantly and actively transported back into the nucleus. The existence of this nucleo-cytoplasmic shuttle mechanism was confirmed by receptor transfer from one nucleus to the other in heterokaryons. Preliminary evidence was obtained, using oestrogen receptor, that this phenomenon may be of general significance for steroid receptors. PMID:1492716

  17. Progesterone promotes propagation and viability of mouse embryonic stem cells.

    PubMed

    Shen, Shan-Wei; Song, Hou-Yan

    2009-10-25

    It has been known that estrogen-17beta stimulates proliferation of mouse embryonic stem (mES) cells. To explore the function of another steroid hormone progesterone, we used MTT method and BrdU incorporation assay to obtain growth curves, clone forming assay to detect the propagation and viability of individual mES cells, Western blot to test the expression of ES cell marker gene Oct-4, fluorescence activated cell sorter (FACS) to test cell cycle, and real-time PCR to detect the expressions of cyclins, cyclin-dependent kinases and proto-oncogenes. The results showed that progesterone promoted proliferation of mES cells. The number of clones was more in progesterone-treated group than that in the control group. The expression of pluripotency-associated transcriptional factor Oct-4 changed little after progesterone treatment as shown by Western blot, indicating that most of mES cells were in undifferentiated state. The results of FACS proved that progesterone promoted DNA synthesis in mES cells. The proportion of mES cells in S+G(2)/M phase was higher in progesterone-treated group than that in the control group. Cyclins and cyclin-dependent kinases, as well as proto-oncogenes (c-myc, c-fos) were up-regulated when cells were treated with progesterone. The results obtained indicate that progesterone promotes propagation and viability of mES cells. The up-regulation of cell cycle-related factors might contribute to the function of progesterone.

  18. Pregnenolone sulfate block of GABA(A) receptors: mechanism and involvement of a residue in the M2 region of the alpha subunit.

    PubMed

    Akk, G; Bracamontes, J; Steinbach, J H

    2001-05-01

    Neurosteroids are produced in the brain, and can have rapid actions on membrane channels of neurons. Pregnenolone sulfate (PS) is a sulfated neurosteroid which reduces the responses of the [gamma]-aminobutyric acid A (GABA(A)) receptor. We analysed the actions of PS on single-channel currents from recombinant GABA(A) receptors formed from [alpha]1, [beta]2 and [gamma]2L subunits. Currents were elicited by a concentration of GABA eliciting a half-maximal response (50 microM) and a saturating concentration (1 mM). PS reduced the duration of clusters of single-channel activity at either concentration of GABA. PS had no discernable effect on rapid processes: no effects were apparent on channel opening and closing, nor on GABA affinity, and a rapidly recovering desensitised state was not affected. Instead, PS produced a slowly developing block which occurred at a similar rate for receptors with open or closed channels and with one or two bound GABA molecules. The rate of block was independent of membrane potential, implying that the charged sulfate moiety does not move through the membrane field. Change in a specific residue near the intracellular end of the channel lining portion of the [alpha]1 subunit had a major effect on the rate of block. Mutation of the residue [alpha]1 V256S reduced the rate of block by 30-fold. A mutation at the homologous position of the [beta]2 subunit ([beta]2 A252S) had no effect, nor did a complementary mutation in the [gamma]2L subunit ([gamma]2L S266A). It seems likely that this residue is involved in a conformational change underlying block by PS, instead of forming part of the binding site for PS.

  19. Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice.

    PubMed

    Ma, Yongjie; Liu, Dexi

    2012-01-01

    Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN) in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues. RT-PCR analysis of genes involved in gluconeogenesis, lipid metabolism and energy homeostasis reveal that PCN treatment on high-fat diet-fed mice reduces expression in the liver of G6Pase, Pepck, Cyp7a1, Cd36, L-Fabp, Srebp, and Fas genes and slightly enhances expression of Cyp27a1 and Abca1 genes. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue show that PCN treatment reduces expression of Pparγ2, Acc1, Cd36, but increases expression of Cpt1b and Pparα genes in mice fed with high-fat diet. Similarly, PCN treatment of animals on high-fat diet increases expression in brown adipose tissue of Pparα, Hsl, Cpt1b, and Cd36 genes, but reduces expression of Acc1 and Scd-1 genes. PXR activation by PCN in high-fat diet fed mice also increases expression of genes involved in thermogenesis in brown adipose tissue including Dio2, Pgc-1α, Pgc-1β, Cidea, and Ucp-3. These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance.

  20. Postnatal expression and induction by pregnenolone-16alpha-carbonitrile of the organic anion-transporting polypeptide 2 in rat liver.

    PubMed

    Guo, Grace L; Johnson, David R; Klaassen, Curtis D

    2002-03-01

    Newborn rats are more sensitive to the toxic effects of cardiac glycosides than are adult rats. This is associated with a decreased ability to remove cardiac glycosides from blood into the liver. Pregnenolone-16alpha-carbonitrile (PCN), a prototypical rodent CYP3A inducer and pregnane-X-receptor (PXR) ligand, stimulates the hepatic clearance of cardiac glycosides in newborn rats, which results in decreased toxicity of the cardiac glycosides. The mechanism responsible for this phenomenon is not clear; however, if elucidated, it would help in understanding and preventing potential drug-drug interactions. The recently cloned rat organic anion-transporting polypeptide 2 (oatp2) (Slc21a5) is a sinusoidal hepatic uptake transporter, with very high affinities for cardiac glycosides, and thus it was hypothesized that rat oatp2 increases during postnatal development and is inducible by PCN. In the present study, livers were removed from Sprague-Dawley rats from postnatal days (pnd) 0 to 45, in 5-day increments; as well as from pnd 10 to 90, in 10-day increments, after PCN (75 mg/kg i.p., for 4 days) or corn oil (vehicle for PCN) treatment. The protein and mRNA levels of rat oatp2 were determined by Western blot analysis and branched DNA signal amplification technique, respectively. Expression of rat oatp2 protein and mRNA increased gradually during postnatal development. PCN treatment increased liver to body weight ratio in both genders, and dramatically accelerated the maturation of hepatic oatp2 protein and mRNA levels. In summary, rat oatp2 undergoes age-dependent and chemical regulation during postnatal development, and is a potential target for drug-drug and age-drug interactions.

  1. Expression of androgen and progesterone receptors in primary human meningiomas.

    PubMed

    Maxwell, M; Galanopoulos, T; Neville-Golden, J; Antoniades, H N

    1993-03-01

    Meningiomas are common brain tumors that show a predilection for females and become more aggressive during pregnancy and menses. The existence of gender-specific hormone receptors in meningiomas has long been a matter of controversy; the recent cloning of androgen, estrogen, and progesterone receptors has facilitated their direct evaluation. The authors have demonstrated the expression of androgen and progesterone receptor messenger ribonucleic acid and protein product in nine primary human meningiomas by Northern blot analysis. Cellular localization was achieved by in situ hybridization analysis. Estrogen receptor expression was not detected. Normal adult meninges were shown to express very low levels of both androgen and progesterone receptors.

  2. Advances in uterine leiomyoma research: the progesterone hypothesis.

    PubMed

    Rein, M S

    2000-10-01

    Uterine leiomyomas are monoclonal tumors. However, the factors involved in their initiation and growth remain poorly understood. The neoplastic transformation of myometrium to leiomyoma likely involves somatic mutations of normal myometrium and the complex interactions of sex steroids and local growth factors. Traditionally, estrogen has been considered the major promoter of myoma growth. The purpose of this review is to highlight the biochemical, histologic, and clinical evidence that supports an equally important role for progesterone in the growth of uterine myomas. Biochemical studies suggest that progesterone, progestins, and the progesterone receptor modulate myoma mitotic activity. A hypothesis to explain the pathogenesis of myomas is presented.

  3. Immunoreactive oestrogens and progesterone in amniotic fluid in twin pregnancies.

    PubMed

    Norman, R J; Joubert, S M

    1985-03-01

    Amniotic fluid concentrations of immunoreactive oestrogens and progesterone were measured at the time of caesarean section in 32 twin pregnancies; 25 women had an elective section and seven were in labour at the time of operation. No significant differences between concentrations in the amniotic fluid of the first and second twin were found in respect of conjugated and unconjugated oestrone, oestradiol, oestriol, oestetrol and unconjugated progesterone either before or during labour. It is unlikely that changes in oestrogens or progesterone in the amniotic fluid are responsible for the selective changes seen in prostaglandins and fetal adrenal steroid during labour in the first twin. PMID:3978052

  4. [Participation of progesterone receptors in plus-maze behavior in female mice].

    PubMed

    Galeeva, A Iu; Pivina, S G; Tuohimaa, P; Ordian, N E

    2006-07-01

    The current study tested delayed effect pf progesterone on the anxiety level of female mice. The elevated plus maze (EPM) behavior was assessed in ovariectomized mice injected for 7 days with estradiol benzoate and progesterone or progesterone alone after 6 hrs of the last treatment. One group of ovariectomized mice was injected with progesterone receptor blocker Mifepristone before 2 hrs of the last treatment. The immunocytochemistry method was used to visualize cells in different brain areas having immunoreactivity (ir) for progesterone receptors. In the EPM, progesterone administration significantly increased the anxiety levels of ovariectomized mice as compared with estradiol benzoate and progesterone administration. The participation of nuclear progesterone receptors in anxiety levels regulation is confirmed by high correlation of the change of progesterone receptor-ir cell number in some brain areas and anxiety levels. Mifepristone decreased anxiety levels and progesterone receptor-ir cell number in both groups of mice that suggests involvement of genomic mechanisms in anxiety regulation in female mice.

  5. Estrogen- and progesterone-induced uterine motility of anestrous goats.

    PubMed

    Verma, O P; Singh, L P

    1976-02-01

    Uterine motility was studied in the anestrous goats after a series of estradiol injections was given and after estradiol-plus-progesterone treatment was administered. Estradiol (0.1 mg/kg) given alone by intramuscular route every 6 hours for 4 continuous days produced only a moderate increase in the uterine contractions during treatment, but significantly higher amplitude and frequency of contractions occurred at 2 days after treatment was stopped. The same doses of estradiol administered for a 24-hour period and followed by 4 injections of progesterone (1.0 mg/kg) given intramuscularly once a day produced a moderate response during treatment, but depressed the amplitude and the frequency of contractions after the treatment was stopped. The results indicate that the tissues primed with estrogen produced a stimulatory effect after their estrogen contents diminished. Progesterone, likewise, produced inhibition after a decrease in the progesterone contents of the uterine tissue. PMID:944003

  6. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  7. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  8. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  9. Role of nuclear progesterone receptor isoforms in uterine pathophysiology

    PubMed Central

    Patel, Bansari; Elguero, Sonia; Thakore, Suruchi; Dahoud, Wissam; Bedaiwy, Mohamed; Mesiano, Sam

    2015-01-01

    BACKGROUND Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key

  10. Uterine activty and plasma progesterone levels in pregnant goats.

    PubMed

    Jones, D E; Kinfton, A

    1977-01-01

    Uterine activity was recorded during the last few weeks of pregnacy in goats, and related to changes in plasma progesterone concentration. In six of the 14 pregnancies, there was little activity until immediately pre-partum, but the remainder showed a progressive increase in uterine motility, particularly during the last seven days of pregnancy. There was a significant correlation between increased uterine activity and decline of peripheral plasma progesterone levels. PMID:841203

  11. Uterine activty and plasma progesterone levels in pregnant goats.

    PubMed

    Jones, D E; Kinfton, A

    1977-01-01

    Uterine activity was recorded during the last few weeks of pregnacy in goats, and related to changes in plasma progesterone concentration. In six of the 14 pregnancies, there was little activity until immediately pre-partum, but the remainder showed a progressive increase in uterine motility, particularly during the last seven days of pregnancy. There was a significant correlation between increased uterine activity and decline of peripheral plasma progesterone levels.

  12. Use of serum progesterone levels to detect pregnancy in elk

    SciTech Connect

    Weber, B.J.; Wolfe, M.L.; White, G.C.

    1982-01-01

    The objective of this investigation was to determine the realibility of serum progesterone assays as a means for detecting pregnancy in elk (Cervus elaphus). The elk were trapped during February through April in the Jemez Mountains of New Mexico. Blood samples were set to Bio-Science Laboratories for projesterone analysis by radioimmunoassay. Levels of progesteron were highly variable within the pregnant and nonpregnant elk. (RJC)

  13. Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage.

    PubMed

    Lei, Beilei; Wang, Haichen; Jeong, Seongtae; Hsieh, Justin T; Majeed, Mohammed; Dawson, Hana; Sheng, Huaxin; Warner, David S; James, Michael L

    2016-01-01

    In models of acute brain injury, progesterone improves recovery through several mechanisms including modulation of neuroinflammation. Secondary injury from neuroinflammation is a potential therapeutic target after intracerebral hemorrhage (ICH). For potential translation of progesterone as a clinical acute ICH therapeutic, the present study sought to define efficacy of exogenous progesterone administration in ICH-relevant experimental paradigms. Young and aged C57BL/6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.05-0.075 U) or autologous whole blood (35 μl) injection. Progesterone at varying doses (4-16 mg/kg) was administered at 2, 5, 24, 48, and 72 h after injury. Rotarod and Morris water maze latencies were measured on days 1-7 and days 28-31 after injury, respectively. Hematoma volume, brain water content (cerebral edema), complementary immunohistochemistry, multiplex cytokine arrays, and inflammatory proteins were assessed at prespecified time points after injury. Progesterone (4 mg/kg) administration improved rotarod and water maze latencies (p < 0.01), and decreased cerebral edema (p < 0.05), microglial proliferation, and neuronal loss (p < 0.01) in young and aged male, young OVX, and aged female mice. Brain concentration of proinflammatory cytokines and Toll-like receptor-associated proteins were also decreased after progesterone (4 mg/kg) treatment (p < 0.01). Progesterone-treated young female mice showed no detectable effects. Exogenous progesterone improved short- and long-term neurobehavioral recovery and modulated neuroinflammation in male and OVX mice after ICH. Future studies should validate these findings, and address timing and length of administration before translation to clinical trial.

  14. Estetrol and utero-placental flow after progesterone load.

    PubMed

    Benassi, L; Alfieri, L; Debiasi, D; Trentadue, R; Salvadori, B

    1982-01-01

    On the basis of recent demonstration in animals of the effect of some hormones on uteroplacental flow, the Authors examined the response of plasmatic Estetrol (15 alpha-hydroxy-estriol) after the administration of progesterone to pregnant women with low Estrogen values. The increase of this compound was related to an improvement of placental function, probably dependent on an increase of available O2, and therefore on uterine blood flow. This can justify a progesterone treatment in such pregnancies. PMID:7168897

  15. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells.

    PubMed

    Bertoni, Ana Paula Santin; Brum, Ilma Simoni; Hillebrand, Ana Caroline; Furlanetto, Tania Weber

    2015-01-01

    Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P < 0.0001; 2.39 times, P = 0.01; 1.58 times, P = 0.0003; and 1.87 times, P < 0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P < 0.0001; 1.75 times, P = 0.037; and 1.95 times, P < 0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P = 0.069). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth. PMID:26089899

  16. Milk fat progesterone concentrations in goats and early pregnancy diagnosis.

    PubMed

    de Montigny, G; Millerioux, P; Jeanguyot, N; Humblot, P; Thibier, M

    1982-04-01

    Blood and milk samples from foremilk during afternoon milking, were simultaneously collected from 285 dairy goats. In experiment 1, fiva cyclic goats were sampled daily for 21 days. In experiment 2, 280 females from 9 flocks were submitted to sampling 21 days after insemination. In addition, some milk samples were divided in two parts, after which one was frozen and the other kept at +4 degrees C until assay. Progesterone concentrations were measured in blood, whole milk and milk fat by radioimmunoassay. No difference in whole milk or fat progesterone levels was found between frozen and refrigerated milk samples. Milk butterfat progesterone concentrations paralleled those in plasma or whole milk throughout the estrous cycle and ranged from about 20 ng/ml at estrus to about 400 ng/ml in mid-luteal phase. The ratio of mid-luteal phase progesterone levels to those seen in the estrous period was over 20 in fat and in blood. This ratio was very much lower in whole milk. Consequently the determination of pregnant and non-pregnant goats from the samples collected 21 days after service was very much easier and accuracy was better when the progesterone content was assayed from milk fat than from whole milk. It was concluded that early pregnancy diagnosis in goats can be done routinely by determination of progesterone levels in milk fat. PMID:16725705

  17. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

    PubMed Central

    Bertoni, Ana Paula Santin; Brum, Ilma Simoni; Hillebrand, Ana Caroline; Furlanetto, Tania Weber

    2015-01-01

    Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P < 0.0001; 2.39 times, P = 0.01; 1.58 times, P = 0.0003; and 1.87 times, P < 0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P < 0.0001; 1.75 times, P = 0.037; and 1.95 times, P < 0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P = 0.069). These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth. PMID:26089899

  18. Progesterone improves porcine in vitro fertilisation system.

    PubMed

    Malo, Clara; Gil, Lydia; Cano, Rafael; Martinez, Felisa; Gonzalez, Noelia

    2014-03-01

    In an effort to improve the quality of in vitro produced porcine embryos, the effect of progestagens - progesterone analogues - on the in vitro developmental competence of porcine oocytes was studied. A total of 1421 in vitro matured oocytes, from 4 replicates, were inseminated with frozen-thawed spermatozoa. Progestagens were added to late maturation and embryo cultures (10 IU/ml). Fertilisation success (pre-maturation, penetration, monospermy and efficiency) and nuclear maturation were evaluated. There were no differences among prematuration rates between groups (P = 0.221). Penetration rates were higher (P < 0.001) in the presence of progestagens (75.0%) as compared to the control (51.7%). However, no differences were observed in monospermy percentages (P = 0.246). The results indicated that supplementation with progestagens increased the efficiency of the in vitro fertilisation system (P < 0.001). An additional beneficial effect was observed in nuclear maturation with progestagens (P = 0.035). In summary, progestagen supplementation is an important factor to improve the in vitro fertilisation procedure.

  19. Progesterone acts via progesterone receptors A and B to regulate breast cancer resistance protein expression.

    PubMed

    Vore, Mary; Leggas, Markos

    2008-03-01

    The breast cancer resistance protein (BCRP; ABCG2) is an ATP-dependent efflux multidrug transporter that belongs to the G family of half-transporters that consist of six transmembrane-spanning domains and must homodimerize to form the active membrane transporter. It is expressed in the apical plasma membrane domain of the small intestine, endothelium, and liver, where it has been shown to play an important role in limiting drug absorption and distribution and in enhancing drug clearance, respectively. BCRP is also expressed in the apical membrane of mammary alveolar epithelia, where it mediates efflux of substrates into milk, and in the placental syncytiotro-phoblasts, where it reduces fetal exposure to these substrates. BCRP substrates include numerous drugs (topotecan, nitrofurantoin, cimetidine) as well as food carcinogens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and the vitamins riboflavin and folic acid. BCRP expression is regulated by a number of nuclear transcription factors, including the peroxisome proliferator-activated receptor-gamma and Hif-1. This issue of Molecular Pharmacology includes a study (p. 845) now conclusively demonstrating that progesterone acts via the progesterone A and B receptors to regulate BCRP expression in a placental cell line.

  20. Determination of estriol, estradiol, estrone, and progesterone in cosmetic products.

    PubMed

    Hubinger, Jean C

    2015-01-01

    This report describes the development and validation of a reverse phase high-performance liquid chromatography (HPLC) method with UV detection for the determination of the hormones estriol, estradiol, estrone, and progesterone in topically applied products. The developed method was then used to conduct a postmarket survey of consumer products for these hormones. Each product was first mixed with Celite and then extracted with methanol. Extracts were cleaned on a Waters Oasis HLB solid phase extraction cartridge, and then analyzed using reversed phase HPLC. The analytes were separated using an Agilent Zorbax Eclipse XDB C8 (5 μm, 250 mm by 4.6 mm) analytical column and detected by their absorbance at 230 nm. Chromatographic separation was achieved by a 1.0-ml/min linear gradient from 30% acetonitrile and 70% water to 80% acetonitrile and 20% water over 30 min. A final 5 min hold time and a re-equilibration time of 10 min were used to prepare the column for subsequent analysis. Recovery from two different brand lotions spiked with three different levels of estriol, estradiol, estrone, and progesterone ranged from 81.8% to 101%. In this study, a total of 70 cosmetic products were surveyed. Twenty two (63%) of the 35 products were labeled as containing an estrogen and/ or progesterone and also provided quantitative label information about the hormone ingredient. The most frequently labeled hormones were progesterone (66%), estriol (46%), estradiol (11%), and estrone (6%). Six products labeled as containing estriol were found to contain estradiol. An estrogen and/or progesterone were found in 34 products at concentrations ranging from 86.0 to 26,800 μg/g. Progesterone was not found in one product labeled as containing this hormone. An additional 35 products, which did not list hormones on their labels, were analyzed and estrogen or progesterone was not detected in these products. PMID:26454975

  1. Uterine Leiomyoma Stem Cells: Linking Progesterone to Growth.

    PubMed

    Bulun, Serdar E; Moravek, Molly B; Yin, Ping; Ono, Masanori; Coon, John S; Dyson, Matthew T; Navarro, Antonia; Marsh, Erica E; Zhao, Hong; Maruyama, Tetsuo; Chakravarti, Debabrata; Kim, J Julie; Wei, Jian-Jun

    2015-09-01

    Uterine leiomyomas (fibroids) represent the most common class of benign tumors in women. Multiple leiomyomas usually arise from the uterus of a symptomatic woman. These tumors cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are responsible for more than 200,000 hysterectomies in the United States annually. Each leiomyoma seems to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a mutation. Tumor expansion is sustained by cell proliferation together with the production of large amounts of extracellular matrix. Estrogen and progesterone stimulate the growth of leiomyomas. Estrogen, together with its receptor ERα, enables progesterone action via induction of progesterone receptor (PR) expression. Progesterone induces the growth of leiomyoma by regulation of a set of key genes that control proliferation and apoptosis. A distinct cell population with stem-progenitor properties is indispensable for progesterone-dependent growth of leiomyomas. This stem-progenitor cell population is deficient in ERα and PR and dependent on the much higher levels of these steroid receptors in surrounding mature leiomyoma or myometrial cells. Progesterone sends paracrine signals from these mature cells to stem cells. The WNT/β-catenin pathway comprises a key component of this paracrine signaling system. The majority of medical treatments currently available for leiomyoma works by inhibiting estrogen or progesterone production or action, but tumors tend to regrow once treatment is stopped. Targeting stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma may lead to the development of more effective therapeutics.

  2. Follicular progesterone elevations with ovulation induction for IVF.

    PubMed

    Kasum, Miro; Simunić, Velimir; Vrčić, Hrvoje; Stanić, Patrik; Orešković, Slavko; Beketić-Orešković, Lidija

    2014-08-01

    The purpose of this review is to analyse the sources and effects of follicular progesterone elevations during ovarian stimulation, with the underlying mechanisms and preventive strategies on the in vitro fertilisation pregnancy outcome. In the early follicular phase, a flare-up effect of gonadotrophin releasing hormone (GnRH) agonists and incomplete luteolysis in GnRH antagonist regimens can result in significant elevations of progesterone. In the late follicular phase, progesterone elevations in GnRH analogue cycles are the result of the ovarian stimulation itself, driven by high follicle stimulating hormone dosage, estradiol levels, the number of follicles and oocytes. It seems that progesterone elevations (> or = 1.5 ng/mL or 4.77 nmol/L) have a detrimental effect on the outcome of pregnancy, accelerating the endometrial maturation. The most appropriate choice to avoid the negative effects of follicular progesterone elevations is to cancel fresh embryo transfer and to transfer frozen-thawed embryos in natural cycles. To prevent follicular phase elevations it might be preferable to use milder stimulation protocols, earlier trigger of ovulation in high responders and single-blastocyst transfer on day 5. The optimal GnRH analogue protocols during the entire stimulation period appear to be the long agonist as well as "long" and long GnRH antagonist regimens.

  3. Selective suppression of endothelial cytokine production by progesterone receptor.

    PubMed

    Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

    2013-01-01

    Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. PMID:23747964

  4. Estradiol and Progesterone have Opposing Roles in the Regulation of Fear Extinction in Female Rats.

    PubMed

    Graham, Bronwyn M; Daher, Melissa

    2016-02-01

    Fear extinction, the laboratory basis of exposure therapy for anxiety disorders, fluctuates across the female rat estrous cycle, where extinction is enhanced during proestrus (high estradiol and progesterone), and impaired during metestrus (low estradiol and progesterone). During the estrous cycle increasing levels of estradiol precede and then overlap with increased levels of progesterone. We sought to isolate the impact of these hormonal changes on fear extinction by systematically treating ovariectomized female rats with estradiol alone, or in combination with progesterone. We found that estradiol alone facilitated extinction recall, whereas the effects of progesterone on estradiol-treated rats were biphasic and dependent on the time interval between progesterone administration and extinction training. Progesterone potentiated estradiol's facilitation of extinction recall when extinction training occurred 6 h after progesterone administration. However, progesterone abolished estradiol's facilitation of extinction recall when extinction training occurred 24 h after progesterone administration. Furthermore, in naturally cycling rats, blocking progesterone receptor activation during proestrus (when progesterone levels peak) prevented the impairment in extinction recall in rats extinguished during metestrus. These results suggest that in naturally cycling females whereas cyclical increases in estradiol facilitate fear extinction, cyclical increases in progesterone may lead to fear extinction impairments. As extinction training took place after the hormonal treatments had been metabolized, we propose that genomic mechanisms may at least partly mediate the impact of cyclic fluctuations in sex hormones on fear extinction.

  5. Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells.

    PubMed

    Vares, Guillaume; Sai, Sei; Wang, Bing; Fujimori, Akira; Nenoi, Mitsuru; Nakajima, Tetsuo

    2015-07-01

    Ionizing radiation and cumulative exposure to steroid hormones are known risk factors for breast cancer. There is increasing evidence that breast tumors are driven by a subpopulation of tumor-initiating cancer stem cells (CSCs). In MCF10A non-cancerous basal-like PR(-) cells, progesterone treatment and X-rays generated ALDH(+) and CD44(+)/CD24(-) CSCs. Here, we report that in irradiated MCF10A cells, progesterone activated the PI3K/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the PI3K/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of PI3K/Akt via mPR resulted in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk in basal cells. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential novel anti-CSC strategies.

  6. Pharmaceutical and clinical development of a novel progesterone formulation.

    PubMed

    Cometti, Barbara

    2015-11-01

    Progesterone plays an essential role in reproductive events. Its use for luteal support in patients undergoing infertility treatment is an established practice. The different routes used to administer progesterone impact on its efficacy in luteal support: oral administration has been shown to be ineffective due to an extensive first-pass metabolism in the liver; vaginal application has a good efficacy but has drawbacks such as vaginal leakage, irritation, discomfort and uncertainty about the real dose adsorbed; finally, intramuscular administration ensures a precise dosage but can be extremely painful with, in some cases, formation of sterile abscesses. A new progesterone preparation is now available in several European and extra-European countries that combines the precise dosage of the injectable formulation with the comfort of a well-tolerated subcutaneous self-administration. The pharmacokinetic and pharmacodynamic properties of this new product are reviewed here, together with the clinical evidence obtained in two multicenter randomized clinical trials. PMID:26342177

  7. Properties of proteins binding plasma progesterone in pregnant Cape porcupines (Hystrix africaeaustralis).

    PubMed

    Louw, A I; van Wyk, V; van Aarde, R J

    1992-09-01

    The properties of progesterone-binding proteins in plasma of pregnant Cape porcupines were investigated using radiolabelled progesterone and either progesterone or cortisol as competing ligands as well as native plasma and heated (60 degrees C for 30 min) plasma. The results demonstrated that plasma from pregnant porcupines contains corticosteroid-binding globulin, but that it constitutes a significant portion of plasma progesterone-binding proteins only during the early stages of pregnancy. Corticosteroid-binding globulin of porcupines appears to be as heat labile as that of guinea-pigs. Concentrations of progesterone-binding proteins in plasma increased during pregnancy to reach concentrations at the eleventh week that were 25 times higher than those of progesterone; concentrations increased significantly (r2 = 0.88) with the increase in progesterone concentration. The results indicate that plasma progesterone-binding proteins in Cape porcupines (Old World hystricomorph) are similar in composition to those in guinea-pigs (New World hystricomorph).

  8. Progesterone directly and rapidly inhibits GnRH neuronal activity via progesterone receptor membrane component 1.

    PubMed

    Bashour, Nicholas Michael; Wray, Susan

    2012-09-01

    GnRH neurons are essential for reproduction, being an integral component of the hypothalamic-pituitary-gonadal axis. Progesterone (P4), a steroid hormone, modulates reproductive behavior and is associated with rapid changes in GnRH secretion. However, a direct action of P4 on GnRH neurons has not been previously described. Receptors in the progestin/adipoQ receptor family (PAQR), as well as progesterone receptor membrane component 1 (PgRMC1) and its partner serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1) mRNA binding protein 1 (SERBP1), have been shown to mediate rapid progestin actions in various tissues, including the brain. This study shows that PgRMC1 and SERBP1, but not PAQR, are expressed in prenatal GnRH neurons. Expression of PgRMC1 and SERBP1 was verified in adult mouse GnRH neurons. To investigate the effect of P4 on GnRH neuronal activity, calcium imaging was used on primary GnRH neurons maintained in explants. Application of P4 significantly decreased the activity of GnRH neurons, independent of secretion of gamma-aminobutyric acidergic and glutamatergic input, suggesting a direct action of P4 on GnRH neurons. Inhibition was not blocked by RU486, an antagonist of the classic nuclear P4 receptor. Inhibition was also maintained after uncoupling of the inhibitory regulative G protein (G(i/o)), the signal transduction pathway used by PAQR. However, AG-205, a PgRMC1 ligand and inhibitor, blocked the rapid P4-mediated inhibition, and inhibition of protein kinase G, thought to be activated downstream of PgRMC1, also blocked the inhibitory activity of P4. These data show for the first time that P4 can act directly on GnRH neurons through PgRMC1 to inhibit neuronal activity.

  9. Estimation of oestrogen and progesterone receptors in chronic rhinitis.

    PubMed

    Wilson, J A; Hawkins, R A; Sangster, K; von Haacke, N P; Tesdale, A; Leese, A M; Murray, J A; Maran, A G

    1986-08-01

    The turbinates of 38 patients with chronic rhinitis were examined biochemically for oestrogen and progesterone receptors. Low levels of oestrogen-receptor-like activity (1-20 fmol/mg protein) were found in 50% of patients of both sexes. Progesterone receptor activity was also weak (1-16 fmol/mg protein) but was present only in 5 female patients. Immunocytochemical assay failed to demonstrate focal areas of oestrogen receptor activity. One juvenile nasopharyngeal angiofibroma was negative for both oestrogen and androgen receptors. Other possible mechanisms of hormonal action are considered.

  10. The putative roles of nuclear and membrane-bound progesterone receptors in the female reproductive tract.

    PubMed

    Kowalik, Magdalena K; Rekawiecki, Robert; Kotwica, Jan

    2013-12-01

    Progesterone produced by the corpus luteum (CL) is a key regulator of normal cyclical reproductive functions in the females of mammalian species. The physiological effects of progesterone are mediated by the canonical genomic pathway after binding of progesterone to its specific nuclear progesterone receptor (PGR), which acts as a ligand-activated transcription factor and has two main isoforms, PGRA and PGRB. These PGR isoforms play different roles in the cell; PGRB acts as an activator of progesterone-responsive genes, while PGRA can inhibit the activity of PGRB. The ratio of these isoforms changes during the estrous cycle and pregnancy, and it corresponds to the different levels of progesterone signaling occurring in the reproductive tract. Progesterone exerts its effects on cells also by a non-genomic mechanism by the interaction with the progesterone-binding membrane proteins including the progesterone membrane component (PGRMC) 1 and 2, and the membrane progestin receptors (mPRs). These receptors rapidly activate the appropriate intracellular signal transduction pathways, and subsequently they can initiate specific cell responses or modulate genomic cell responses. The diversity of progesterone receptors and their cellular actions enhances the role of progesterone as a factor regulating the function of the reproductive system and other organs. This paper deals with the possible involvement of nuclear and membrane-bound progesterone receptors in the function of target cells within the female reproductive tract.

  11. Ovine maternal nutrient restriction from mid to late gestation decreases heptic progesterone inactivating enzyme activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we have shown increased concentrations of progesterone and decreased liver weight in mid to late pregnant ewes provided a nutrient restricted vs. adequate diet. This alteration in peripheral progesterone could be due to increased synthesis and/or decreased clearance of progesterone. There...

  12. Glucocorticoid and progesterone receptors in yolk sac placenta.

    PubMed

    Carbone, J P; Baldridge, R C; Magen, A B; Andrew, C L; Koszalka, T R; Brent, R L

    1986-01-01

    The parietal yolk sac (PYS) of the rat fetus at the 14th day of gestation contains glucocorticoid as well as progesterone receptors; both are present in the trophoblast cell layer. Following heat activation the receptors are capable of binding to deoxyribonucleic acid- (DNA-)cellulose. Glucocorticoid receptors, but not progesterone receptors, are also present in the visceral yolk sac (VYS) at the 14th day of gestation. Greater amounts (some 250 femtomoles/mg cytosol protein) of a glucocorticoid receptor are present in the VYS on the 17th day of gestation. The Kd is approximately 4 X 10(-9) M; following activation it also binds to DNA-cellulose. The elution pattern of the activated VYS receptor from diethylaminoethyl-(DEAE-)Sephadex, however, is similar to that found with kidney and colon rather than that of liver (i.e., it resembles corticosteroid binder IB rather than binder II) indicating a possible role in transport. Although the receptors are separate entities, progesterone competes as effectively as corticosterone for binding to the glucocorticoid receptors in both the PYS and and VYS, thus raising the question of the possible effect of changes in progesterone concentrations on the functioning of glucocorticoids during development.

  13. Progesterone Regulation of Synaptic Transmission and Plasticity in Rodent Hippocampus

    ERIC Educational Resources Information Center

    Foy, Michael R.; Akopian, Garnik; Thompson, Richard F.

    2008-01-01

    Ovarian hormones influence memory formation by eliciting changes in neural activity. The effects of various concentrations of progesterone (P4) on synaptic transmission and plasticity associated with long-term potentiation (LTP) and long-term depression (LTD) were studied using in vitro hippocampal slices. Extracellular studies show that the…

  14. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL...

  15. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone intravaginal inserts. 529.1940 Section 529.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS CERTAIN OTHER DOSAGE FORM NEW ANIMAL DRUGS §...

  16. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

    PubMed

    Thomas, Peter; Pang, Yefei

    2013-06-01

    The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation.

  17. Protective actions of progesterone in the cardiovascular system: potential role of membrane progesterone receptors (mPRs) in mediating rapid effects.

    PubMed

    Thomas, Peter; Pang, Yefei

    2013-06-01

    The protective functions of progesterone in the cardiovascular system have received little attention even though evidence has accumulated that progesterone lowers blood pressure, inhibits coronary hyperactivity and has powerful vasodilatory and natriuretic effects. One possible reason why potential beneficial actions of progesterone on cardiovascular functions have not been extensively studied is that divergent effects to those of progesterone have been observed in many clinical trials with synthetic progestins such as medroxyprogesterone acetate which are associated with increased risk of coronary disease. Evidence that progesterone exerts protective effects on cardiovascular functions is briefly reviewed. The finding that progesterone administration decreases blood vessel vasoconstriction in several animal models within a few minutes suggests that rapid, nongenomic progesterone mechanisms are of physiological importance in regulating vascular tone. Rapid activation of second messenger pathways by progesterone has been observed in vascular endothelial and smooth muscle cells, resulting in alterations in endothelial nitric oxide synthase (eNOS) activity and calcium influx, respectively. Both nuclear progesterone receptors (PRs) and novel membrane progesterone receptors (mPRs) are candidates for the intermediaries in these rapid, cell-surface initiated progesterone actions in endothelial and smooth muscle vascular cells. PRs have been detected in both cell types. New data are presented showing mPRα, mPRβ and mPRγ are also present in human endothelial and smooth muscle vascular cells. Preliminary evidence suggests mPRs mediate rapid progestin signaling in these endothelial cells, resulting in down-regulation of cAMP production and increased nitric oxide synthesis. The role of mPRs in progesterone regulation of cardiovascular functions warrants further investigation. PMID:23357432

  18. The Effects of Sugammadex on Progesterone Levels in Pregnant Rats

    PubMed Central

    Et, Tayfun; Topal, Ahmet; Erol, Atilla; Tavlan, Aybars; Kılıçaslan, Alper; Uzun, Sema Tuncer

    2015-01-01

    Background: Sugammadex has been shown to decrease the efficiency of progesterone-containing oral contraceptive drugs which possess a steroid structure. Aims: The aim of the present study was to evaluate the effects of sugammadex on progesterone levels in pregnant rats as well as on the physiological course of the pregnancy. Study Design: Animal experiment. Methods: This study was approved by the Selçuk University Ethical Committee for Experimental Animal Research. Pregnant Winster Albino rats (n=26) were divided into three groups and administered with various intravenous injections on the 7th day of pregnancy. The control group (Group K, n=6) received 1.5 mL serum physiologic, the sugammadex group (Group S, n=10) received 30 mg/kg sugammadex and the sugammadex + rocuronium group (Group SR, n=10) received 30 mg/kg sugammadex and 3.5 mg/kg rocuronium. Progesterone levels were measured and the offspring were monitored for morphologic status. Results: Mean progesterone levels were 94.16±15.54 ng/mL in Group K, 87.86±12.48 ng/mL in Group S, and 94.53±16.10 ng/mL in Group SR (p>0.05). No stillbirth or miscarriage was observed in the rats. The mean number of offspring was 6.8±1.47 in Group K, 6.5±1.35 in Group S, and 6.4±1.17 in Group SR. The offspring appeared macroscopically normal. Conclusion: Sugammadex does not appear to affect the progesterone levels in pregnant rats in the first trimester and the clinical course. Successful completion of pregnancy and the absence of stillbirth or miscarriage will guide future studies about the use of sugammadex, particularly in the first trimester of the pregnancy. PMID:26167346

  19. The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21.

    PubMed

    Auchus, Richard J; Sampath Kumar, A; Andrew Boswell, C; Gupta, Manisha K; Bruce, Kristen; Rath, Nigam P; Covey, Douglas F

    2003-01-01

    Human cytochrome P450c17 (17alpha-hydroxylase, 17,20-lyase) (CYP17) and cytochrome P450c21 (21-hydroxylase) (CYP21) differ by only 14 amino acids in length and share 29% amino acid identity. Both enzymes hydroxylate progesterone at carbon atoms that lie only 2.6A apart, but CYP17 also metabolizes other steroids and demonstrates additional catalytic activities. To probe the active site topologies of these related enzymes, we synthesized the enantiomer of progesterone and determined if ent-progesterone is a substrate or inhibitor of CYP17 and CYP21. Neither enzyme metabolizes ent-progesterone; however, ent-progesterone is a potent competitive inhibitor of CYP17 (K(I)=0.2 microM). The ent-progesterone forms a type I difference spectrum with CYP17, but molecular dynamics simulations suggest different binding orientations for progesterone and its enantiomer. The ent-progesterone also inhibits CYP21, with weaker affinity than for CYP17. We conclude that CYP17 accommodates the stereochemically unnatural ent-progesterone better than CYP21. Enantiomeric steroids can be used to probe steroid binding sites, and these compounds may be effective inhibitors of steroid biosynthesis.

  20. Selective progesterone receptor modulators (SPRMs): progesterone receptor action, mode of action on the endometrium and treatment options in gynecological therapies

    PubMed Central

    Wagenfeld, Andrea; Saunders, Philippa T.K.; Whitaker, Lucy; Critchley, Hilary O.D.

    2016-01-01

    ABSTRACT Introduction: The progesterone receptor plays an essential role in uterine physiology and reproduction. Selective progesterone receptor modulators (SPRMs) have emerged as a valuable treatment option for hormone dependent conditions like uterine fibroids, which have a major impact on women’s quality of life. SPRMs offer potential for longer term medical treatment and thereby patients may avoid surgical intervention. Areas covered: The authors have reviewed the functional role of the progesterone receptor and its isoforms and their molecular mechanisms of action via genomic and non-genomic pathways. The current knowledge of the interaction of the PR and different SPRMs tested in clinical trials has been reviewed. The authors focused on pharmacological effects of selected SPRMs on the endometrium, their anti-proliferative action, and their suppression of bleeding. Potential underlying molecular mechanisms and the specific histological changes in the endometrium induced by SPRMs (PAEC; Progesterone receptor modulator Associated Endometrial Changes) have been discussed. The clinical potential of this compound class including its impact on quality of life has been covered. Expert Opinion: Clinical studies indicate SPRMs hold promise for treatment of benign gynecological complaints (fibroids, heavy menstrual bleeding; HMB). There however remains a knowledge gap concerning mechanism of action. PMID:27138351

  1. Use of monoclonal antibodies for radioimmunoassay of water buffalo milk progesterone.

    PubMed

    Capparelli, R; Iannelli, D; Bordi, A

    1987-11-01

    In order to standardize a radioimmunoassay of milk progesterone as a routine method for confirmation of oestrus and diagnosis of pregnancy in water buffalo, monoclonal antibodies against progesterone were produced. Hybridomas were prepared by fusing spleen cells from a Balb/c mouse immunized with progesterone 11 alpha-hemisuccinate-bovine serum albumin conjugate with the mouse myeloma cell line NS-1. Thirty wells out of 94 secreted anti-progesterone antibodies. Of the ten independent hybridomas derived, one (AF65) was suitable for the quantification of milk progesterone by radioimmunoassay. The tracer used in the assay was progesterone-11 alpha-hemisuccinate [( 2-125I]iodohistamine). The sensitivity of the assay was 50 pg/tube. The mean progesterone concentration at oestrus was 0.8 +/- 0.2 ng/ml increasing to 8.5 +/- 0.8 ng/ml 24 d later in pregnant animals.

  2. Progesterone and threatened abortion: a randomized clinical trial on endocervical cytokine concentrations.

    PubMed

    Alimohamadi, Shohreh; Javadian, Pouya; Gharedaghi, Mohammad Hadi; Javadian, Nima; Alinia, Hossein; Khazardoust, Soghra; Borna, Sedigheh; Hantoushzadeh, Sedigheh

    2013-06-01

    The purpose of this study was to investigate the effect of vaginal progesterone on endocervical cytokine concentration in women at risk of threatened abortion. One hundred and sixty pregnant women with clinical symptoms of threatened abortion before the 20th week of pregnancy were randomly assigned to receive vaginal progesterone or placebo. Cervical fluids were collected and endocervical concentrations of different cytokines (IFNγ, TNFα, IL-8, IL-10 and IL-12) were analyzed before and one week after progesterone or placebo treatment. A significant decrease in IFNγ and increase in IL-10 in endocervical fluid was seen when the values were compared before and after progesterone treatment. However, there were no significant differences in pregnancy outcomes between the placebo and progesterone groups. We conclude that despite the failure of vaginal progesterone treatment to improve pregnancy outcomes, progesterone can induce a shift in the concentration of cytokines in endocervical secretions. PMID:23489467

  3. Short communication: Plasma progesterone concentration and ovarian dynamics of lactating Jersey cows treated with 1 or 2 intravaginal progesterone inserts.

    PubMed

    Moraes, João G N; Silva, Paula R B; Bortoletto, Nathália; Scanavez, Alexandre L A; Chebel, Ricardo C

    2016-03-01

    The objectives of the current experiment were to determine circulating progesterone concentrations and ovarian follicle development of lactating Jersey cows treated with 1 or 2 controlled internal drug release (CIDR) insert containing 1.38 g of progesterone during proestrus. Cows were enrolled in the experiment at 34 ± 3 d in milk and were paired by parity, body condition score, body weight, and milk yield. Estrous cycles were presynchronized with an injection of GnRH concurrent with a new CIDR insert (study d -7) and 2 injections of PGF2α given 5 and 6 d after the GnRH injection (study d -2 and -1, respectively). Cows assigned to the 1CIDR treatment (n=30) or 2CIDR treatment (n=30) received 1 and 2 CIDR inserts, respectively, from study d 0 through 7. Control cows (n=10) did not receive further treatment. On study d -2 and daily from study d 0 through 7, ovaries were examined by transrectal ultrasound and blood samples were collected for determination of progesterone. On study d 7, CIDR inserts were removed after ultrasound exam and blood sample collection. Progesterone concentration from study d 0 through 7 was greatest for 2CIDR cows (2.17 ± 0.09 ng/mL), followed by 1CIDR cows (1.37 ± 0.10 ng/mL) and control cows (0.62 ± 0.21 ng/mL). The interaction between treatment and study day affected progesterone concentration from study d 0 through 7. The average increase in progesterone concentration from study d 1 through 7 was 0.80 ng/mL for 1CIDR and 1.72 ng/mL for 2CIDR cows compared with control cows. The percentage of cows that ovulated between study d 0 and 7 was greatest for control cows (80%), but it did not differ between 1CIDR (12%) and 2CIDR (3.7%) cows. Growth of class III follicles (10-17 mm) identified on study d 0 was affected by treatment because 1CIDR cows had larger class III follicles than 2CIDR cows on study d 5, 6 and 7. A larger proportion of control cows developed a new follicular wave between study d 0 and 7 (control=60.0%, 1CIDR=12.0%, 2

  4. Very Early Administration of Progesterone for Acute Traumatic Brain Injury

    PubMed Central

    Wright, David W.; Yeatts, Sharon D.; Silbergleit, Robert; Palesch, Yuko Y.; Hertzberg, Vicki S.; Frankel, Michael; Goldstein, Felicia C.; Caveney, Angela F.; Howlett-Smith, Harriet; Bengelink, Erin M.; Manley, Geoffrey T.; Merck, Lisa H.; Janis, L. Scott; Barsan, William G.

    2015-01-01

    BACKGROUND Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Progesterone has been shown to improve neurologic outcome in multiple experimental models and two early-phase trials involving patients with TBI. METHODS We conducted a double-blind, multicenter clinical trial in which patients with severe, moderate-to-severe, or moderate acute TBI (Glasgow Coma Scale score of 4 to 12, on a scale from 3 to 15, with lower scores indicating a lower level of consciousness) were randomly assigned to intravenous progesterone or placebo, with the study treatment initiated within 4 hours after injury and administered for a total of 96 hours. Efficacy was defined as an increase of 10 percentage points in the proportion of patients with a favorable outcome, as determined with the use of the stratified dichotomy of the Extended Glasgow Outcome Scale score at 6 months after injury. Secondary outcomes included mortality and the Disability Rating Scale score. RESULTS A total of 882 of the planned sample of 1140 patients underwent randomization before the trial was stopped for futility with respect to the primary outcome. The study groups were similar with regard to baseline characteristics; the median age of the patients was 35 years, 73.7% were men, 15.2% were black, and the mean Injury Severity Score was 24.4 (on a scale from 0 to 75, with higher scores indicating greater severity). The most frequent mechanism of injury was a motor vehicle accident. There was no significant difference between the progesterone group and the placebo group in the proportion of patients with a favorable outcome (relative benefit of progesterone, 0.95; 95% confidence interval [CI], 0.85 to 1.06; P = 0.35). Phlebitis or thrombophlebitis was more frequent in the progesterone group than in the placebo group (relative risk, 3.03; CI, 1.96 to 4.66). There were no significant differences in the other prespecified safety outcomes. CONCLUSIONS This clinical trial did not show a

  5. Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics, physiology and potential for perimenopause.

    PubMed

    Prior, J C

    2011-01-01

    Perimenopause, women's normal midlife reproductive transition, is highly symptomatic for about 20% of women who are currently inaccurately counseled and inappropriately treated with oral contraceptives, menopausal hormone therapy or hysterectomy. About 80% of perimenopausal women experience vasomotor symptoms (VMS), 25% have menorrhagia, and about 10% experience mastalgia. The majority of women describe varying intensities of sleep, -coping or mood difficulties. Women are more symptomatic because common knowledge inaccurately says that estradiol (E2) levels are dropping/deficient. Evidence shows that with disturbed brain-ovary feedbacks, E2 levels average 26% higher and soar erratically - some women describe feeling pregnant! Also, ovulation and progesterone (P4) levels become insufficient or absent. The most symptomatic women have higher E2 and lower P4 levels. Because P4 and E2 complement/counterbalance each other's tissue effects, oral micronized P4 (OMP4 300 mg at -bedtime) is a physiological therapy for treatment-seeking, symptomatic perimenopausal women. Given cyclically (cycle d 14-27, or 14 on/off) in menstruating midlife women, OMP4 decreases cyclic VMS, improves sleep and premenstrual mastalgia. Menorrhagia is treated with ibuprofen 200mg/6h plus OMP4 cycle d 4-28. For insulin resistance, metformin plus cyclic or daily OMP4 decreases insulin resistance and weight gain. Non-responsive migraines need daily OMP4 plus usual therapies. VMS and insomnia in late perimenopause respond to daily OMP4. In summary, OMP4 is a physiology-based therapy that improves sleep, treats VMS, does not increase breast proliferation or cancer risk, increases bone formation and has beneficial cardiovascular effects. A controlled trial is testing OMP4 for perimenopausal VMS - more evidence-based data are needed. PMID:24753856

  6. Progesterone for Symptomatic Perimenopause Treatment – Progesterone politics, physiology and potential for perimenopause

    PubMed Central

    Prior, J.C.

    2011-01-01

    Perimenopause, women’s normal midlife reproductive transition, is highly symptomatic for about 20% of women who are currently inaccurately counseled and inappropriately treated with oral contraceptives, menopausal hormone therapy or hysterectomy. About 80% of perimenopausal women experience vasomotor symptoms (VMS), 25% have menorrhagia, and about 10% experience mastalgia. The majority of women describe varying intensities of sleep, coping or mood difficulties. Women are more symptomatic because common knowledge inaccurately says that estradiol (E2) levels are dropping/deficient. Evidence shows that with disturbed brain-ovary feedbacks, E2 levels average 26% higher and soar erratically – some women describe feeling pregnant! Also, ovulation and progesterone (P4) levels become insufficient or absent. The most symptomatic women have higher E2 and lower P4 levels. Because P4 and E2 complement/counterbalance each other’s tissue effects, oral micronized P4 (OMP4 300 mg at bedtime) is a physiological therapy for treatment-seeking, symptomatic perimenopausal women. Given cyclically (cycle d 14-27, or 14 on/off) in menstruating midlife women, OMP4 decreases cyclic VMS, improves sleep and premenstrual mastalgia. Menorrhagia is treated with ibuprofen 200mg/6h plus OMP4 cycle d 4-28. For insulin resistance, metformin plus cyclic or daily OMP4 decreases insulin resistance and weight gain. Non-responsive migraines need daily OMP4 plus usual therapies. VMS and insomnia in late perimenopause respond to daily OMP4. In summary, OMP4 is a physiology-based therapy that improves sleep, treats VMS, does not increase breast proliferation or cancer risk, increases bone formation and has beneficial cardiovascular effects. A controlled trial is testing OMP4 for perimenopausal VMS – more evidence-based data are needed. PMID:24753856

  7. Stress-induced progesterone secretion and progesterone receptor immunoreactivity in the paraventricular nucleus are modulated by pubertal development in male rats.

    PubMed

    Romeo, Russell D; Bellani, Rudy; McEwen, Bruce S

    2005-12-01

    Male rats show a differential adrenocortical response to stress before and after pubertal development, such that prepubertal animals have a more prolonged stress-induced corticosterone response compared to adults. Whether pubertal maturation affects other adrenocortical responses to stress is currently unknown. To address this question, we assessed stress-induced progesterone secretion in both intact and gonadectomized prepubertal (28 days of age) and adult (77 days of age) male rats either before or after exposure to a 30 min session of restraint stress. We found that prepubertal males show a greater and more prolonged stress-induced progesterone response compared to adults. We also found a similar effect in castrated prepubertal and adult males, indicating the differential stress-induced progesterone response is not gonadal in origin. We also examined progesterone receptor (PR) levels by immunohistochemistry in the paraventricular nucleus (PVN) of the hypothalamus, a key regulatory nucleus of the hypothalamic-pituitary-adrenal (HPA) axis, and found lower PR protein expression in the PVN of prepubertal compared to adult males. These data indicate that in addition to corticosterone, stress-induced adrenocortical progesterone levels are differentially affected by pubertal maturation. Furthermore, these data raise the possibility of different progesterone sensitivity of the PVN before and after puberty. The significance of this differential response is presently unknown. However, given the pleiotropic effects of progesterone on male physiology and behaviour, it is likely that the disparate post-stress exposure to progesterone affects the prepubertal and adult male differently.

  8. Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females.

    PubMed

    Hall, Olivia J; Limjunyawong, Nathachit; Vermillion, Meghan S; Robinson, Dionne P; Wohlgemuth, Nicholas; Pekosz, Andrew; Mitzner, Wayne; Klein, Sabra L

    2016-09-01

    Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load. Progesterone treatment promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular proliferation, reducing protein leakage into the airway, improving pulmonary function, and upregulating the epidermal growth factor amphiregulin (AREG) in the lungs. Administration of rAREG to progesterone-depleted females promoted pulmonary repair and improved the outcome of IAV infection. Progesterone-treatment of AREG-deficient females could not restore protection, indicating that progesterone-mediated induction of AREG caused repair in the lungs and accelerated recovery from IAV infection. Repair and production of AREG by damaged respiratory epithelial cell cultures in vitro was increased by progesterone. Our results illustrate that progesterone is a critical host factor mediating production of AREG by epithelial cells and pulmonary tissue repair following infection, which has important implications for women's health. PMID:27631986

  9. Tightly bound nuclear progesterone receptor is not phosphorylated in primary chick oviduct cultures.

    PubMed Central

    Garcia, T; Jung-Testas, I; Baulieu, E E

    1986-01-01

    Oviduct cells from estradiol-treated chicks were grown in primary culture. After 3-5 days of culture in medium containing estradiol, 90% of the cellular progesterone binding sites were detected in the cytosol. After exposure to [3H]progesterone at 37 degrees C, 80% of the progesterone binding sites were found in nuclear fractions. Progesterone receptor phosphorylation was assessed after incubating the cells with [32P]orthophosphate. Receptor components were immunoprecipitated with a specific polyclonal antibody (IgG-G3) and analyzed by NaDodSO4/PAGE and autoradiography. In the cytosol, constant amounts of 32P-labeled 110-kDa subunit (the B subunit, one of the progesterone-binding components of the receptor) and of the non-steroid-binding heat shock protein hsp90 were found, whether cells had been exposed to progesterone or not. No 32P-labeled 79-kDa subunit (the A subunit, another progesterone-binding subunit) was detected. Various procedures were used to solubilize nuclear progesterone receptor (0.5 M KCl, micrococcal nuclease, NaDodSO4), and in no case was 32P-labeled B subunit detected in the extracts. However, nonradioactive B subunit was detected by immunoblot in a nuclear KCl extract of progesterone-treated cells. These results suggest that the fraction of the B subunit that becomes strongly attached to nuclear structures is not phosphorylated upon exposure of cells to progesterone. Images PMID:3463987

  10. Ovarian cycle approach by rectal temperature and fecal progesterone in a female killer whale, Orcinus orca.

    PubMed

    Kusuda, Satoshi; Kakizoe, Yuka; Kanda, Koji; Sengoku, Tomoko; Fukumoto, Yohei; Adachi, Itsuki; Watanabe, Yoko; Doi, Osamu

    2011-01-01

    This study aimed to validate the measurements of body temperature and fecal progesterone concentrations as minimally invasive techniques for assessing ovarian cycle in a single sexually mature female killer whale. Rectal temperature data, fecal and blood samples were collected in the dorsal position using routine husbandry training on a voluntary basis. The correlations between rectal temperature and plasma progesterone concentration and between fecal and plasma progesterone concentrations were investigated. Fecal progesterone metabolites were identified by a combination of high-performance liquid chromatography and enzyme immunoassay. Plasma progesterone concentrations (range: 0.2-18.6 ng/ml) and rectal temperature (range: 35.3-35.9°C) changed cyclically, and cycle lengths were an average (±SD) of 44.9±4.0 days (nine cycles) and 44.6±5.9 days (nine cycles), respectively. Rectal temperature positively correlated with the plasma progesterone concentrations (r=0.641, P<0.01). There was a visual trend for fecal progesterone profiles to be similar to circulating plasma progesterone profiles. Fecal immunoreactive progestagen analysis resulted in a marked immunoreactive peak of progesterone. The data from the single killer whale indicate that the measurement of rectal temperature is suitable for minimally invasive assessment of the estrous cycle and monitoring the fecal progesterone concentration is useful to assess ovarian luteal activity.

  11. Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair and Recovery in Females

    PubMed Central

    Vermillion, Meghan S.; Robinson, Dionne P.; Pekosz, Andrew; Mitzner, Wayne

    2016-01-01

    Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside of the reproductive tract have not been evaluated. Administration of exogenous progesterone (at concentrations that mimic the luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment altered the inflammatory environment of the lungs, but had no effects on viral load. Progesterone treatment promoted faster recovery by increasing TGF-β, IL-6, IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular proliferation, reducing protein leakage into the airway, improving pulmonary function, and upregulating the epidermal growth factor amphiregulin (AREG) in the lungs. Administration of rAREG to progesterone-depleted females promoted pulmonary repair and improved the outcome of IAV infection. Progesterone-treatment of AREG-deficient females could not restore protection, indicating that progesterone-mediated induction of AREG caused repair in the lungs and accelerated recovery from IAV infection. Repair and production of AREG by damaged respiratory epithelial cell cultures in vitro was increased by progesterone. Our results illustrate that progesterone is a critical host factor mediating production of AREG by epithelial cells and pulmonary tissue repair following infection, which has important implications for women’s health. PMID:27631986

  12. Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

    PubMed Central

    Kim, J. Julie; Kurita, Takeshi

    2013-01-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

  13. TReP-132 Is a Novel Progesterone Receptor Coactivator Required for the Inhibition of Breast Cancer Cell Growth and Enhancement of Differentiation by Progesterone

    PubMed Central

    Gizard, Florence; Robillard, Romain; Gross, Barbara; Barbier, Olivier; Révillion, Françoise; Peyrat, Jean-Philippe; Torpier, Gérard; Hum, Dean W.; Staels, Bart

    2006-01-01

    The sex steroid progesterone is essential for the proliferation and differentiation of the mammary gland epithelium during pregnancy. In relation to this, in vitro studies using breast carcinoma T47D cells have demonstrated a biphasic progesterone response, consisting of an initial proliferative burst followed by a sustained growth arrest. However, the transcriptional factors acting with the progesterone receptor (PR) to mediate the progesterone effects on mammary cell growth and differentiation remain to be determined. Recently, it has been demonstrated that the transcriptional regulating protein of 132 kDa (TReP-132), initially identified as a regulator of steroidogenesis, is also a cell growth suppressor. Similar to progesterone-bound PR, TReP-132 acts by inducing the gene expression of the G1 cyclin-dependent kinase inhibitors p21WAF1/Cip1 (p21) and p27Kip1 (p27). The putative interaction between TReP-132 and progesterone pathways in mammary cells was therefore analyzed in the present study. Our results show that TReP-132 interacts in vitro and in T47D cells with progesterone-activated PR. TReP-132 synergizes with progesterone-bound PR to trans activate the p21 and p27 gene promoters at proximal Sp1-binding sites. Moreover, TReP-132 overexpression and knockdown, respectively, increased or prevented the induction of p21 and p27 gene expression by progesterone. As a consequence, TReP-132 knockdown also resulted in the loss of the inhibitory effects of progesterone on pRB phosphorylation, G1/S cell cycle progression, and cell proliferation. Furthermore, the knockdown of TReP-132 expression also prevented the induction of both early and terminal markers of breast cell differentiation which had been previously identified as progesterone target genes. As well, the progesterone-induced accumulation of lipid vacuoles was inhibited in the TReP-132-depleted cells. Finally, TReP-132 gene expression levels increased following progesterone treatment, indicating the

  14. Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

    PubMed Central

    Hess, Kathryn; Jeitziner, Rachel

    2015-01-01

    Worldwide, breast cancer incidence has been increasing for decades. Exposure to reproductive hormones, as occurs with recurrent menstrual cycles, affects breast cancer risk, and can promote disease progression. Exogenous hormones and endocrine disruptors have also been implicated in increasing breast cancer incidence. Numerous in vitro studies with hormone-receptor-positive cell lines have provided insights into the complexities of hormone receptor signaling at the molecular level; in vivo additional layers of complexity add on to this. The combined use of mouse genetics and tissue recombination techniques has made it possible to disentangle hormone action in vivo and revealed that estrogens, progesterone, and prolactin orchestrate distinct developmental stages of mammary gland development. The 2 ovarian steroids that fluctuate during menstrual cycles act on a subset of mammary epithelial cells, the hormone-receptor-positive sensor cells, which translate and amplify the incoming systemic signals into local, paracrine stimuli. Progesterone has emerged as a major regulator of cell proliferation and stem cell activation in the adult mammary gland. Two progesterone receptor targets, receptor activator of NfκB ligand and Wnt4, serve as downstream paracrine mediators of progesterone receptor-induced cell proliferation and stem cell activation, respectively. Some of the findings in the mouse have been validated in human ex vivo models and by next-generation whole-transcriptome sequencing on healthy donors staged for their menstrual cycles. The implications of these insights into the basic control mechanisms of mammary gland development for breast carcinogenesis and the possible role of endocrine disruptors, in particular bisphenol A in this context, will be discussed below. PMID:26241069

  15. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    SciTech Connect

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K.

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  16. Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis.

    PubMed

    Brisken, Cathrin; Hess, Kathryn; Jeitziner, Rachel

    2015-10-01

    Worldwide, breast cancer incidence has been increasing for decades. Exposure to reproductive hormones, as occurs with recurrent menstrual cycles, affects breast cancer risk, and can promote disease progression. Exogenous hormones and endocrine disruptors have also been implicated in increasing breast cancer incidence. Numerous in vitro studies with hormone-receptor-positive cell lines have provided insights into the complexities of hormone receptor signaling at the molecular level; in vivo additional layers of complexity add on to this. The combined use of mouse genetics and tissue recombination techniques has made it possible to disentangle hormone action in vivo and revealed that estrogens, progesterone, and prolactin orchestrate distinct developmental stages of mammary gland development. The 2 ovarian steroids that fluctuate during menstrual cycles act on a subset of mammary epithelial cells, the hormone-receptor-positive sensor cells, which translate and amplify the incoming systemic signals into local, paracrine stimuli. Progesterone has emerged as a major regulator of cell proliferation and stem cell activation in the adult mammary gland. Two progesterone receptor targets, receptor activator of NfκB ligand and Wnt4, serve as downstream paracrine mediators of progesterone receptor-induced cell proliferation and stem cell activation, respectively. Some of the findings in the mouse have been validated in human ex vivo models and by next-generation whole-transcriptome sequencing on healthy donors staged for their menstrual cycles. The implications of these insights into the basic control mechanisms of mammary gland development for breast carcinogenesis and the possible role of endocrine disruptors, in particular bisphenol A in this context, will be discussed below. PMID:26241069

  17. Non-canonical Progesterone Signaling in Granulosa Cell Function

    PubMed Central

    Peluso, John J.; Pru, James K.

    2014-01-01

    It has been known for over three decades that progesterone (P4) suppresses follicle growth. It has been assumed that P4 acts directly on granulosa cells of developing follicles to slow their development, since P4 inhibits both mitosis and apoptosis of cultured granulosa cells. However, granulosa cells of developing follicles of mice, rats, monkeys and humans do not express the A or B form of the classic nuclear receptor for progesterone (PGR). In contrast, these granulosa cells express other progesterone binding proteins, one of which is referred to as Progesterone Receptor Membrane Component 1 (PGRMC1). PGRMC1 specifically binds P4 with high affinity and mediates P4’s anti-mitotic and anti-apoptotic action as evidenced by the lack of these P4-dependent effects in PGRMC1-depleted cells. In addition, mice in which PGRMC1 is conditionally depleted in granulosa cells show diminished follicle development. While the mechanism through which P4 activation of PGRMC1 affects granulosa cell function is not well defined, it appears that PGRMC1 controls granulosa cell function in part by regulating gene expression in T cell specific transcription factor/lymphoid enhancer factor (Tcf/Lef)-dependent manner. Clinically, altered PGRMC1 expression has been correlated with premature ovarian failure/insufficiency, polycystic ovarian syndrome and infertility. These collective studies provide strong evidence that PGRMC1 functions as a receptor for P4 in granulosa cells and that altered expression results in compromised reproductive capacity. Ongoing studies seek to define the components of the signal transduction cascade through which P4-activation of PGRMC1 results in the regulation of granulosa cell function. PMID:24516175

  18. Transcriptional regulation of genes related to progesterone production.

    PubMed

    Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

    2015-01-01

    Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production. PMID:26135521

  19. Interaction of progesterone receptor with immobilized adenosine triphosphate.

    PubMed

    Moudgil, V K; Toft, D O

    1977-02-22

    Affinity chromatography has been used to study the binding of ATP to cyto-plasmic progesterone receptors of hen oviduct. A resin which selectively binds the receptor protein was prepared by linking ATP covalently to Sepharose 4B through a 6-carbon bridge of adipic acid dihydrazide. Receptor bound to the affinity resin was recovered in a single peak upon gradient elution with KCl (0.2-1 M) or ATP (0-0.1 M). While affinity chromatography was normally accomplished using the [3H]progesterone receptor complex, the hormone was not necessary for ATP binding under the conditions employed. The chromatography of crude receptor preparations allowed up to 100-fold purification with greater than 80% recovery of the receptor. The semipurified receptor appeared intact when analysed by sucrose gradient centrifugation, polyacrylamide gel electrophoresis, and DEAE-cellulose chromatography. The latter procedure separated the receptor into two components, A and B, both of which were capable of binding ATP. Although a specific biochemical role of ATP in hormone receptor action has not been demonstrated, the present studies support this possibility and, in addition, offer a convenient and reliable step for the purification of progesterone receptors. PMID:836885

  20. Inhibition of human placental progesterone synthesis by danazol in vivo.

    PubMed

    Rabe, T; Kiesel, L; Franke, C; Runnebaum, B; Mösch, R; Nobakht, N

    1984-01-01

    In vivo, a single dose of 1000 mg danazol was given orally to pregnant volunteers (n = 8) prior to a therapeutic abortion (8th-12th week of gestation). Changes in serum progesterone and estradiol were evaluated both by analysis of percentage values related to initial concentrations or statistically by a Kruskal-Wallis test comparing absolute steroid concentrations. Following treatment (n = 8), a significant decrease in mean plasma progesterone of about 20% was observed within 2-4 hours; progesterone levels varied between 80-120% during 24 hours in controls (n = 10); individual serum estradiol decreased up to 30% of control values 2 hours after danazol application. Changes in estradiol in controls versus tests were not statistically significant (p less than 0.05) when absolute estradiol concentrations were compared. Only a slight (10-20%) decrease in mean serum DHAS was found between 2 to 6 hours following danazol treatment. This study demonstrates the inhibitory activity of danazol on the human maternal and fetal steroidogenesis in vivo. The possible sites of action of danazol are discussed.

  1. MOLECULAR MECHANISMS INVOLVED IN PROGESTERONE RECEPTOR REGULATION OF UTERINE FUNCTION

    PubMed Central

    Lee, K.; Jeong, J.; Tsai, M.-J.; Tsai, S.; Lydon, J. P.; DeMayo, F. J.

    2007-01-01

    The ovarian steroid hormone progesterone is a major regulator of uterine function. The actions of this hormone is mediated through its cognate receptor, the progesterone receptor, Pgr. Ablation of the Pgr has shown that this receptor is critical for all female reproductive functions including the ability of the uterus to support and maintain the development of the implanting mouse embryo. High density DNA microarray analysis has identified direct and indirect targets of Pgr action. One of the targets of Pgr action is a member of the Hedgehog morphogen Indian hedgehog, Ihh. Ihh and members of the Hh signaling cascade show a coordinate expression pattern in the mouse uterus during the preimplantation period of pregnancy. The expression of Ihh and its receptor Patched-1, Ptc1, as well as, down stream targets of Ihh-Ptch1 signaling, such as the orphan nuclear receptor COUP-TF II show that this morphogen pathway mediates communication between the uterine epithelial and stromal compartments. The members of the Ihh signaling axis may function to coordinate the proliferation, vascularization and differentiation of the uterine stroma during pregnancy. This analysis demonstrates that progesterone regulates uterine function in the mouse by coordinating the signals from the uterine epithelium to stroma in the preimplantation mouse uterus. PMID:17067792

  2. Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

    PubMed Central

    Garcia-Ovejero, Daniel; González, Susana; Paniagua-Torija, Beatriz; Lima, Analía; Molina-Holgado, Eduardo; De Nicola, Alejandro F.

    2014-01-01

    Abstract Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury. PMID:24460450

  3. Role of progesterone and progestin therapy in threatened abortion and preterm labour.

    PubMed

    Szekeres-Bartho, Julia; Wilczynski, Jacek R; Basta, Pawel; Kalinka, Jaroslaw

    2008-01-01

    Progesterone (P) has been widely used in an attempt to prevent threatened miscarriage, recurrent miscarriage and pre-term labour. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". Along with its endocrine effects, P also acts as an "immunosteroid", by controlling the bias towards a pregnancy protective immune milieu. A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Progesterone plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors. At high concentrations, progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. The possible mechanisms by which progesterone contributes to the maintenance of early and late pregnancy are discussed. PMID:17981685

  4. Elevated Progesterone Levels on the Day of Oocyte Maturation May Affect Top Quality Embryo IVF Cycles

    PubMed Central

    Huang, Bo; Ren, Xinling; Wu, Li; Zhu, Lixia; Xu, Bei; Li, Yufeng; Ai, Jihui; Jin, Lei

    2016-01-01

    In contrast to the impact of elevated progesterone on endometrial receptivity, the data on whether increased progesterone levels affects the quality of embryos is still limited. This study retrospectively enrolled 4,236 fresh in vitro fertilization (IVF) cycles and sought to determine whether increased progesterone is associated with adverse outcomes with regard to top quality embryos (TQE). The results showed that the TQE rate significantly correlated with progesterone levels on the day of human chorionic gonadotropin (hCG) trigger (P = 0.009). Multivariate linear regression analysis of factors related to the TQE rate, in conventional IVF cycles, showed that the TQE rate was negatively associated with progesterone concentration on the day of hCG (OR was -1.658, 95% CI: -2.806 to -0.510, P = 0.005). When the serum progesterone level was within the interval 2.0–2.5 ng/ml, the TQE rate was significantly lower (P <0.05) than when the progesterone level was < 1.0 ng/ml; similar results were obtained for serum progesterone levels >2.5 ng/ml. Then, we choose a progesterone level at 1.5ng/ml, 2.0 ng/ml and 2.5 ng/ml as cut-off points to verify this result. We found that the TQE rate was significantly different (P <0.05) between serum progesterone levels < 2.0 ng/ml and >2.0 ng/ml. In conclusion, the results of this study clearly demonstrated a negative effect of elevated progesterone levels on the day of hCG trigger, on TQE rate, regardless of the basal FSH, the total gonadotropin, the age of the woman, or the time of ovarian stimulation. These data demonstrate that elevated progesterone levels (>2.0 ng/ml) before oocyte maturation were consistently detrimental to the oocyte. PMID:26745711

  5. Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections.

    PubMed

    Ragupathy, Viswanath; Xue, Wang; Tan, Ji; Devadas, Krishnakumar; Gao, Yamei; Hewlett, Indira

    2016-10-01

    In human immunodeficiency virus type 1 (HIV-1)-infected women, oral or injectable progesterone containing contraceptive pills may enhance HIV-1 acquisition in vivo, and the mechanism by which this occurs is not fully understood. In developing countries, Herpes simplex virus type-2 (HSV-2) co-infection has been shown to be a risk for increase of HIV-1 acquisition and, if co-infected women use progesterone pills, infections may increase several fold. In this study, we used an in vitro cell culture system to study the effects of progesterone on HIV-1 replication and to explore the molecular mechanism of progesterone effects on infected cells. In our in vitro model, CEMss cells (lymphoblastoid cell line) were infected with either HIV-1 alone or co-infected with HSV-2. HIV-1 viral load was measured with and without sex hormone treatment. Progesterone-treated cells showed an increase in HIV-1 viral load (1411.2 pg/mL) compared with cells without progesterone treatment (993.1 pg/mL). Increased cell death was noted with HSV-2 co-infection and in progesterone-treated cells. Similar observations were noted in peripheral blood mononuclear cells (PBMC) cells derived from three female donors. Progesterone-treated cells also showed reduced antiviral efficacy. Inflammatory cytokines and associations with biomarkers of disease progression were explored. Progesterone upregulated inflammatory cytokines and chemokines conversely and downregulated anti-apoptotic Bcl-2 expression. Nuclear protein analysis by electrophoretic mobility shift assay showed the association of progesterone with progesterone response element (PRE), which may lead to downregulation of Bcl-2. These data indicate that progesterone treatment enhances HIV-1 replication in infected cells and co-infection with HSV-2 may further fuel this process. PMID:27538988

  6. Neuroactive Steroids in First-Episode Psychosis: A Role for Progesterone?

    PubMed Central

    Pagotto, Uberto; Bonora, Elena; Triolo, Federico; Chiri, Luigi; Menchetti, Marco; Mondelli, Valeria; Pariante, Carmine; Berardi, Domenico

    2016-01-01

    Neuroactive steroids may play a role in the pathophysiology of psychotic disorders, but few studies examined this issue. We compared serum levels of cortisol, testosterone, dehydroepiandrosterone, and progesterone between a representative sample of first-episode psychosis (FEP) patients and age- and gender-matched healthy subjects. Furthermore, we analyzed the associations between neuroactive steroids levels and the severity of psychotic symptom dimensions. Male patients had lower levels of progesterone than controls (p = 0.03). Progesterone levels were inversely associated with the severity of positive symptoms (p = 0.007). Consistent with preclinical findings, results suggest that progesterone might have a role in the pathophysiology of psychotic disorders. PMID:27747103

  7. Absence of progesterone effects on chlamydial genital infection in female guinea pigs.

    PubMed

    Pasley, J N; Rank, R G; Hough, A J; Cohen, C; Barron, A L

    1985-01-01

    The effect of progesterone alone and in combination with estradiol was investigated in ovariectomized and gonadally intact female guinea pigs infected with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). The course of the infection, as determined by the percentage of cells with GPIC (chlamydia) inclusions in Giemsa-stained vaginal scrapings, was not affected in animals receiving 5.0 mg of progesterone daily. Progesterone had no influence on the enhancement of infection by estradiol. In comparison with sesame oil-treated controls, infection was prolonged by four to six days (P less than .05) in animals receiving a combination of 5.0 mg of progesterone plus 1.0 microgram of estradiol or 1.0 microgram of estradiol alone each day. In ovariectomized animals, estradiol delayed the appearance of IgA antibody in genital secretions, whereas progesterone alone had no effect. Guinea pigs treated with estradiol or progesterone plus estradiol manifested an acute endometritis not observed in animals treated with progesterone alone or in controls receiving sesame oil. Although cervical ectopy, analogous to that seen in women with high levels of progesterone, was identified by histopathology in animals treated with progesterone, no enhancement of the chlamydial infection was observed.

  8. Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition

    PubMed Central

    Tan, Huiqing; Yi, Lijuan; Rote, Neal S.; Hurd, William W.

    2012-01-01

    Context: Progesterone promotes uterine relaxation during pregnancy and its withdrawal induces labor. Progesterone withdrawal in human parturition is mediated in part by changes in the relative levels of the nuclear progesterone receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves myometrial inflammation; however, the functional link between nuclear PR-mediated progesterone actions and inflammation in human myometrial cells is unclear. Objective: Our objective was to determine how PR-A and PR-B regulate progesterone action in human myometrial cells and specifically the expression of genes encoding contraction-associated proteins and proinflammatory mediators. Design: Effects of PR-A and PR-B on the capacity for progesterone to modulate gene expression was determined using an immortalized human myometrial cell line stably transfected with inducible PR-A and PR-B expression transgenes and conditioned to express various PR-A and PR-B levels. Gene expression was assessed by genome wide transcriptome analysis, quantitative RT-PCR and immunoblotting. Results: PR-A and PR-B were each transcriptionally active in response to progesterone and affected the expression of distinct gene cohorts. The capacity for progesterone to affect gene expression was dependent on the PR-A to PR-B ratio. This was especially apparent for the expression of proinflammatory genes. Progesterone decreased proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and increased proinflammatory gene expression when the ratio favored PR-A. Progesterone via PR-B increased expression of inhibitor-κBα, a repressor of the nuclear factor-κB transcription factor, and inhibited basal and lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B-mediated effects were inhibited by PR-A. Conclusions: Our data suggest that during most of human pregnancy, when myometrial cells are PR-B dominant, progesterone promotes myometrial quiescence through PR

  9. Progesterone Synthesis in the Nervous System: Implications for Myelination and Myelin Repair

    PubMed Central

    Schumacher, Michael; Hussain, Rashad; Gago, Nathalie; Oudinet, Jean-Paul; Mattern, Claudia; Ghoumari, Abdel M.

    2011-01-01

    Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair. PMID:22347156

  10. Progesterone receptor gene variants and risk of endometrial cancer

    PubMed Central

    O'Mara, Tracy A.; Fahey, Paul; Ferguson, Kaltin; Marquart, Louise; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Amant, Frederic; Hall, Per; Liu, Jianjun; Czene, Kamila; Rebbeck, Timothy R.; Ahmed, Shahana; Dunning, Alison M.; Gregory, Catherine S.; Shah, Mitul; Webb, Penelope M.; Spurdle, Amanda B.

    2011-01-01

    Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3′ region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12–1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3′ untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant. PMID:21148628

  11. The cytoskeleton and the cellular traffic of the progesterone receptor.

    PubMed

    Perrot-Applanat, M; Lescop, P; Milgrom, E

    1992-10-01

    Previous studies on glucocorticoid receptors have suggested the existence of interactions between the receptor and microtubule or actin networks. It was hypothesized that such interactions may contribute to the guidance of steroid hormone receptors towards the nucleus. We used a permanent L cell line expressing the delta 638-642 progesterone receptor. This mutant has all the characteristics of the wild type receptor except that the deletion of five amino acids inactivates the constitutive karyophilic signal. Consequently, the receptor is cytoplasmic in the absence of hormone but is shifted into the nucleus when administration of hormone activates the second karyophilic signal. Optical microscopy and confocal laser microscopy were used in intact cells or in cells depleted of soluble elements by permeabilization with detergents. By immunofluorescence, the receptor was found to be mainly concentrated in the perinuclear area. A small fraction of progesterone receptor (PR) persisted in this region after Triton X100 treatment. These observations suggested that the receptor could interact with some insoluble constituent(s) of the cytoplasm. However, careful colocalization studies showed that this heterogenous distribution was not due to interactions with microtubule, microfilament, or intermediate filament networks. Functional involvement of these networks in the translocation of the receptor into the nucleus was studied after cell treatment with cytoskeletal drugs such as nocodazole, demecolcine and cytochalasin. None of these compounds prevented or even delayed the hormone-dependent transfer of delta 638-642 PR into the nucleus. Similar conclusions were reached with the wild type receptor expressed by transfection in Cos-7 cells. PR was shifted from the nucleus into the cytoplasm by administration of energy-depleting drugs. After disruption of the various cytoskeletal networks normal nuclear reaccumulation of the receptor was observed when these drugs were removed. The

  12. Boots for Achilles: progesterone's reduction of cholesterol is a second-order adaptation.

    PubMed

    Amir, Dorsa; Fessler, Daniel M T

    2013-06-01

    Progesterone and cholesterol are both vital to pregnancy. Among other functions, progesterone downregulates inflammatory responses, allowing for maternal immune tolerance of the fetal allograft. Cholesterol a key component of cell membranes, is important in intracellular transport, cell signaling, nerve conduction, and metabolism Despite the importance of each substance in pregnancy, one exercises an antagonistic effect on the other, as periods of peak progesterone correspond with reductions in cholesterol availability, a consequence of progesterone's negative effects on cholesterol biosynthesis. This arrangement is understandable in light of the threat posed by pathogens early in pregnancy. Progesterone-induced immunomodulation entails increased vulnerability to infection, an acute problem in the first trimester, when fetal development is highly susceptible to insult. Many pathogens rely on cholesterol for cell entry, egress, and replication. Progesterone's antagonistic effects on cholesterol thus partially compensate for the costs entailed by progesterone-induced immunomodulation. Among pathogens to which the host's vulnerability is increased by progesterone's effects, approximately 90% utilize cholesterol, and this is notably true of pathogens that pose a risk during pregnancy. In addition to having a number of possible clinical applications, our approach highlights the potential importance of second-order adaptations, themselves a consequence of the lack of teleology in evolutionary processes. PMID:23909226

  13. Sphenoid wing meningioma progression after placement of a subcutaneous progesterone agonist contraceptive implant.

    PubMed

    Piper, J G; Follett, K A; Fantin, A

    1994-04-01

    A causal relationship between sex steroids and meningioma proliferation has long been suspected. We report a case of the clinical progression of a sphenoid wing meningioma after the placement of Norplant, a subcutaneous contraceptive implant containing levonorgestrel, a progesterone agonist. Although not proof of causation, this observation lends further credence to the importance of progesterone receptors in the growth and possible treatment of meningiomas.

  14. Secretion of progesterone and 20 alpha-dihydroprogesterone during pregnancy in goats.

    PubMed

    Sawada, T; Nakatani, T; Tamada, H; Mori, J

    1994-08-01

    The relationships between the secretion of progesterone and 20 alpha-dihydroprogesterone and the sites of their production in pregnant goats were investigated. The progesterone concentration in the peripheral plasma increased after the goats mated, and was high from day 10 to day 140 of pregnancy. The 20 alpha-dihydroprogesterone concentration increased gradually from day 0 to day 140 after mating. The progesterone concentration before parturition decreased rapidly on day 1 prepartum, but the 20 alpha-dihydroprogesterone concentration remained high until the day of parturition and then began to fall. The ratio of progesterone to 20 alpha-dihydroprogesterone decreased and fell to less than one on day 1 prepartum. The plasma concentrations of progesterone in ovarian vein and of 20 alpha-dihydroprogesterone in the ovarian vein, umbilical vein, and umbilical artery were higher than those in the jugular vein. The ratio of progesterone to 20 alpha-dihydroprogesterone in placental tissue was less than one. These results suggest that in pregnant goats the main production site is the ovary for progesterone and the ovary and feto-placental unit for 20 alpha-dihydroprogesterone, and 20 alpha-dihydroprogesterone may take help to regulate progesterone production within the ovary and the feto-placental unit. PMID:7985207

  15. Immune Aspects and Myometrial Actions of Progesterone and CRH in Labor

    PubMed Central

    Vrachnis, Nikolaos; Malamas, Fotodotis M.; Sifakis, Stavros; Tsikouras, Panayiotis; Iliodromiti, Zoe

    2012-01-01

    Progesterone and corticotropin-releasing hormone (CRH) have a critical role in pregnancy and labor, as changes related to these hormones are crucial for the transition from myometrial quiescence to contractility. The mechanisms related to their effect differ between humans and other species, thus, despite extensive research, many questions remain to be answered regarding their mediation in human labor. Immune responses to progesterone and CRH are important for labor. Progesterone acts as an immunomodulator which controls many immune actions during pregnancy, and its withdrawal releases the inhibitory action on inflammatory pathways. In humans, a “functional” progesterone withdrawal occurs with onset of labor through changes in progesterone metabolism, progesterone receptors, and other molecules that either facilitate or antagonize progesterone function. Placental CRH acts on the fetal pituitary-adrenal axis to stimulate adrenal production of androgens and cortisol and also acts directly on myometrial cells via its receptors. CRH also affects inflammatory signals and vice versa. Interactions between progesterone and CRH additionally occur during labor. We describe the role of these two hormones in human myometrium and their interactions with the immune system during labor. PMID:22028729

  16. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    PubMed

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin. PMID:25092805

  17. Progesterone and Nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex

    PubMed Central

    el-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2014-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation and axonal degeneration. Current therapies are limited to immunomodulators and anti-inflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2+ oligodendrocyte progenitor cells and CA II+ mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin. PMID:25092805

  18. Plasma membrane mediated action of progesterone in amphibian (Rana dybowskii) oocyte maturation.

    PubMed

    Bandyopadhyay, A; Bandyopadhyay, J; Choi, H H; Choi, H S; Kwon, H B

    1998-03-01

    The mechanism of progesterone action within the ovarian follicle was investigated in Rana dybowskii, by using immobilized progesterone. Fluorescein isothiocyanate-labeled progesterone 3-O-carboxymethyloxime-BSA (P-BSA) was localized on the outside surface of the denuded oocyte, which indicated that P-BSA did not cross the barrier of cell surface. Progesterone-BSA induced germinal vesicle breakdown (GVBD) of denuded oocytes in a dose-dependent manner but failed to induce GVBD of follicle wall-enclosed oocytes. The time course of P-BSA-induced GVBD in denuded oocytes was similar to that observed with progesterone. Furthermore, both P-BSA and progesterone induced oocyte maturation in the presence of RU486, a well-known nuclear progesterone receptor antagonist. Treatment of denuded oocytes with P-BSA resulted in a threefold increase in inositol triphosphate (IP3) and a fourfold increase in diacylglycerol levels within 10 min. Additionally protein kinase C (PKC) activity was markedly increased by 30 min of incubation following exposure to P-BSA. Such changes were not observed in denuded oocytes exposed to beta-estradiol-6-O-carboxymethyloxime-BSA, which failed to induce GVBD. These results suggest that progesterone acts initially at the oocyte surface where it triggers generation of membrane-mediated second messengers during oocyte maturation in amphibians.

  19. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    PubMed

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  20. Contrasting effects of progesterone on fertility of dairy and beef cows.

    PubMed

    Stevenson, J S; Lamb, G C

    2016-07-01

    The role of progesterone in maintaining pregnancy is well known in the bovine. Subtle differences exist between dairy and beef cows because of differing concentrations of progesterone during recrudescence of postpartum estrous cycles, rate of follicular growth and maturation, proportions of 2- and 3-follicular wave cycles, and other effects on pregnancy outcomes per artificial insemination (P/AI). Because proportions of anovulatory cows before the onset of the artificial insemination (AI) period are greater and more variable in beef (usually ranging from 30 to 70%) than dairy (25%) cows, AI programs were developed to accommodate anovulatory and cycling beef cows enrolled therein. Incorporating a progestin as part of an AI program in beef cows improved P/AI by reducing the proportion of cows having premature luteal regression and short post-AI luteal phases. In both genotypes, prolonged dominant follicle growth in a reduced progesterone milieu resulted in increased (1) LH pulses, (2) preovulatory follicle diameter, and (3) concentrations of estradiol and a subsequently larger corpora lutea (CL). In contrast, the progesterone milieu during growth of the ovulatory follicle in an ovulation control program does not seem to affect subsequent P/AI in beef cows, whereas in dairy cows follicle development in an elevated compared with a low progesterone environment increases P/AI. Progesterone status in beef cows at the onset of ovulation synchronization is not related to P/AI in multiparous cows, whereas P/AI was suppressed in primiparous cows that began a timed AI program in a low-progesterone environment. In timed AI programs, elevated concentrations of progesterone just before PGF2α and reduced concentrations at AI are critical to maximizing subsequent P/AI in dairy cows, but seemingly much less important in beef cows. By inducing ancillary CL and increasing concentrations of progesterone, human chorionic gonadotropin may increase P/AI when administered to beef cows 7d

  1. Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro

    PubMed Central

    Jin, Yong-Xun; Kwon, Jeong-Woo

    2016-01-01

    Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression.

  2. Estrogen and Progesterone hormone receptor expression in oral cavity cancer

    PubMed Central

    Biegner, Thorsten; Teriete, Peter; Hoefert, Sebastian; Krimmel, Michael; Munz, Adelheid; Reinert, Siegmar

    2016-01-01

    Background Recent studies have shown an increase in the incidence of oral squamous cell carcinoma (OSCC) in younger patients. The hypothesis that tumors could be hormonally induced during pregnancy or in young female patients without the well-known risk factors alcohol or tobacco abuse seems to be plausible. Material and Methods Estrogen Receptor alpha (ERα) and Progesterone Receptor (PR) expression were analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen. OSCCs were stratified in a young female (n=7) study cohort and older patients (n=46). In the young female study cohort three patients (n=3/7) developed OSCC during or shortly after pregnancy. Breast cancer tissues were used as positive control for ERα and PR expression. Results ERα expression was found in four oral precursor lesions (squamous intraepithelial neoplasia, SIN I-III, n=4/35, 11%) and in five OSCC specimen (n=5/46, 11%). The five ERα positive OSCC samples were older male patients. All patients within the young female study cohort were negatively stained for both ERα and PR. Conclusions ER expression could be regarded as a seldom risk factor for OSCC. PR expression seems to be not relevant for the development of OSCC. Key words:Oral squamous cell carcinoma, estrogen receptor, progesterone receptor, hormone receptor. PMID:27475696

  3. Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro

    PubMed Central

    Jin, Yong-Xun; Kwon, Jeong-Woo

    2016-01-01

    Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression. PMID:27672508

  4. Modeling of Progesterone Release from Poly(3-Hydroxybutyrate) (PHB) Membranes.

    PubMed

    Romero, Analia I; Bermudez, José M; Villegas, Mercedes; Dib Ashur, María F; Parentis, Mónica L; Gonzo, Elio E

    2016-08-01

    Poly(3-hydroxybutyrate) (PHB) biodegradable polymeric membranes were evaluated as platform for progesterone (Prg)-controlled release. In the design of new drug delivery systems, it is important to understand the mass transport mechanism involved, as well as predict the process kinetics. Drug release experiments were conducted and the experimental results were evaluated using engineering approaches that were extrapolated to the pharmaceutical field by our research group. Membranes were loaded with different Prg concentrations and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). SEM images showed that membranes have a dense structure before and after the progesterone addition. DSC and FTIR allowed determining the influence of the therapeutic agent in the membrane properties. The in vitro experiments were performed using two different techniques: (A) returning the sample to the receptor solution (constant volume of the delivery medium) and (B) extracting total volume of the receptor solution. In this work, we present a simple and accurate "lumped" second-order kinetic model. This lumped model considers the different mass transport steps involved in drug release systems. The model fits very well the experimental data using any of the two experimental procedures, in the range 0 ≤ t ≤ ∞ or 0 ≤ M t  ≤ M ∞. The drug release analysis using our proposed approaches is relevant for establishing in vitro-in vivo correlations in future tests in animals.

  5. Modeling of Progesterone Release from Poly(3-Hydroxybutyrate) (PHB) Membranes.

    PubMed

    Romero, Analia I; Bermudez, José M; Villegas, Mercedes; Dib Ashur, María F; Parentis, Mónica L; Gonzo, Elio E

    2016-08-01

    Poly(3-hydroxybutyrate) (PHB) biodegradable polymeric membranes were evaluated as platform for progesterone (Prg)-controlled release. In the design of new drug delivery systems, it is important to understand the mass transport mechanism involved, as well as predict the process kinetics. Drug release experiments were conducted and the experimental results were evaluated using engineering approaches that were extrapolated to the pharmaceutical field by our research group. Membranes were loaded with different Prg concentrations and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). SEM images showed that membranes have a dense structure before and after the progesterone addition. DSC and FTIR allowed determining the influence of the therapeutic agent in the membrane properties. The in vitro experiments were performed using two different techniques: (A) returning the sample to the receptor solution (constant volume of the delivery medium) and (B) extracting total volume of the receptor solution. In this work, we present a simple and accurate "lumped" second-order kinetic model. This lumped model considers the different mass transport steps involved in drug release systems. The model fits very well the experimental data using any of the two experimental procedures, in the range 0 ≤ t ≤ ∞ or 0 ≤ M t  ≤ M ∞. The drug release analysis using our proposed approaches is relevant for establishing in vitro-in vivo correlations in future tests in animals. PMID:26729524

  6. Role of phosphorylation in progesterone receptor signaling and specificity.

    PubMed

    Hagan, Christy R; Daniel, Andrea R; Dressing, Gwen E; Lange, Carol A

    2012-06-24

    Progesterone receptors (PR), in concert with peptide growth factor-initiated signaling pathways, initiate massive expansion of the epithelial cell compartment associated with the process of alveologenesis in the developing mammary gland. PR-dependent signaling events also contribute to inappropriate proliferation observed in breast cancer. Notably, PR-B isoform-specific cross talk with growth factor-driven pathways is required for the proliferative actions of progesterone. Indeed, PRs act as heavily phosphorylated transcription factor "sensors" for mitogenic protein kinases that are often elevated and/or constitutively activated in invasive breast cancers. In addition, phospho-PR-target genes frequently include the components of mitogenic signaling pathways, revealing a mechanism for feed-forward signaling that confers increased responsiveness of, PR +mammary epithelial cells to these same mitogenic stimuli. Understanding the mechanisms and isoform selectivity of PR/kinase interactions may yield further insight into targeting altered signaling networks in breast and other hormonally responsive cancers (i.e. lung, uterine and ovarian) in the clinic. This review focuses on PR phosphorylation by mitogenic protein kinases and mechanisms of PR-target gene selection that lead to increased cell proliferation.

  7. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis

    PubMed Central

    Li, Xiang; Rhee, David K.; Malhotra, Rajeev; Mayeur, Claire; Hurst, Liam A.; Ager, Emily; Shelton, Georgia; Kramer, Yael; McCulloh, David; Keefe, David; Bloch, Kenneth D.; Bloch, Donald B.; Peterson, Randall T.

    2015-01-01

    Iron homeostasis is tightly regulated by the membrane iron exporter ferroportin and its regulatory peptide hormone hepcidin. The hepcidin/ferroportin axis is considered a promising therapeutic target for the treatment of diseases of iron overload or deficiency. Here, we conducted a chemical screen in zebrafish to identify small molecules that decrease ferroportin protein levels. The chemical screen led to the identification of 3 steroid molecules, epitiostanol, progesterone, and mifepristone, which decrease ferroportin levels by increasing the biosynthesis of hepcidin. These hepcidin-inducing steroids (HISs) did not activate known hepcidin-inducing pathways, including the BMP and JAK/STAT3 pathways. Progesterone receptor membrane component-1 (PGRMC1) was required for HIS-dependent increases in hepcidin biosynthesis, as PGRMC1 depletion in cultured hepatoma cells and zebrafish blocked the ability of HISs to increase hepcidin mRNA levels. Neutralizing antibodies directed against PGRMC1 attenuated the ability of HISs to induce hepcidin gene expression. Inhibiting the kinases of the SRC family, which are downstream of PGRMC1, blocked the ability of HISs to increase hepcidin mRNA levels. Furthermore, HIS treatment increased hepcidin biosynthesis in mice and humans. Together, these data indicate that PGRMC1 regulates hepcidin gene expression through an evolutionarily conserved mechanism. These studies have identified drug candidates and potential therapeutic targets for the treatment of diseases of abnormal iron metabolism. PMID:26657863

  8. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis.

    PubMed

    Li, Xiang; Rhee, David K; Malhotra, Rajeev; Mayeur, Claire; Hurst, Liam A; Ager, Emily; Shelton, Georgia; Kramer, Yael; McCulloh, David; Keefe, David; Bloch, Kenneth D; Bloch, Donald B; Peterson, Randall T

    2016-01-01

    Iron homeostasis is tightly regulated by the membrane iron exporter ferroportin and its regulatory peptide hormone hepcidin. The hepcidin/ferroportin axis is considered a promising therapeutic target for the treatment of diseases of iron overload or deficiency. Here, we conducted a chemical screen in zebrafish to identify small molecules that decrease ferroportin protein levels. The chemical screen led to the identification of 3 steroid molecules, epitiostanol, progesterone, and mifepristone, which decrease ferroportin levels by increasing the biosynthesis of hepcidin. These hepcidin-inducing steroids (HISs) did not activate known hepcidin-inducing pathways, including the BMP and JAK/STAT3 pathways. Progesterone receptor membrane component-1 (PGRMC1) was required for HIS-dependent increases in hepcidin biosynthesis, as PGRMC1 depletion in cultured hepatoma cells and zebrafish blocked the ability of HISs to increase hepcidin mRNA levels. Neutralizing antibodies directed against PGRMC1 attenuated the ability of HISs to induce hepcidin gene expression. Inhibiting the kinases of the SRC family, which are downstream of PGRMC1, blocked the ability of HISs to increase hepcidin mRNA levels. Furthermore, HIS treatment increased hepcidin biosynthesis in mice and humans. Together, these data indicate that PGRMC1 regulates hepcidin gene expression through an evolutionarily conserved mechanism. These studies have identified drug candidates and potential therapeutic targets for the treatment of diseases of abnormal iron metabolism. PMID:26657863

  9. Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro.

    PubMed

    Yuan, Bao; Liang, Shuang; Jin, Yong-Xun; Kwon, Jeong-Woo; Zhang, Jia-Bao; Kim, Nam-Hyung

    2016-01-01

    Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression. PMID:27672508

  10. The place of selective progesterone receptor modulators in myoma therapy.

    PubMed

    Donnez, Jacques; Donnez, Olivier; Courtoy, Guillaume E; Dolmans, Marie M

    2016-06-01

    Uterine fibroids are the most commonly encountered benign uterine tumors in women of reproductive age. As progesterone is known to play a key role in promoting myoma growth, the goal of the study was to analyze the efficacy of selective progesterone receptor modulators (SPRMs). From four studies, it was concluded that UPA (ulipristal acetate) treatment was able to control myoma-associated uterine bleeding in over 90% of cases and significantly reduce myoma volume in more than 80% of women. The results of long-term intermittent therapy (PEARL III and PEARL IV studies) (4 courses of 3 months) demonstrated that more than one course of UPA is able to maximize its potential benefits in terms of control of bleeding and fibroid volume reduction. The treatment was considered safe, even at the level of endometrial changes. With the advent of SPRMs, new algorithms should be discussed, as there is no doubt that there is a place for medical therapy with SPRMs in the current armamentarium of fibroid management. PMID:26930390

  11. A simple pharmacokinetic model linking plasma progesterone concentrations with the hormone released from bovine intravaginal inserts.

    PubMed

    Mariano, R N; Turino, L N; Cabrera, M I; Scándolo, D E; Maciel, M G; Grau, R J A

    2010-10-01

    On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect.

  12. Milk progesterone radioimmunoassay using radioiodinated tracers: a rapid and reliable assay system

    SciTech Connect

    Espinosa, J.; Botana, L.M.; Puentes, E.; Regueiro, B.J.

    1984-09-01

    Both the validity and practicability of a direct progesterone radioimmunoassay based on radioiodinated progesterone tracers were studied. The results obtained show the reliability of the assay; when compared with assays based on /sup 3/H-progesterone tracers there are fewer steps for assay execution, saving time and reducing the number of reagents used. Various commercially available /sup 125/I-progesterone tracers were assayed, and only those with an 11 alpha-hemisuccinate bridge were suitably bound by antisera raised against progesterone-bovine serum albumin conjugates having identical bridge structure. The bridge effect caused no observable alteration in validity parameters. Finally, the results support the utility of this assay as a practical method of early diagnosis of pregnancy and as a reliable experimental technique to monitor cow ovarian function.

  13. Outcome of vaginal progesterone as a tocolytic agent: randomized clinical trial.

    PubMed

    Saleh Gargari, Soraya; Habibolahi, Malihe; Zonobi, Zahra; Khani, Zahra; Sarfjoo, Fatemeh Sadat; Kazemi Robati, Atefeh; Etemad, Roja; Karimi, Zohreh

    2012-01-01

    Vaginal progesterone has a potential beneficial effect in postponing of preterm labor by suppression of prostaglandins cascades. Although different studies evaluated the use of progesterone for preterm birth, the exact effect of which on prolongation of pregnancy remains unclear. Seventy two women who underwent preterm labor were managed by magnesium sulfate. Then they were randomly assigned to continue pregnancy either by applying vaginal progesterone (400 mg) until delivery or without using any drug. Gestational age mean at the time of delivery (P = 0.039) and postponing delivery mean time (P = 0.048) were significantly higher in progesterone group. Comparison of neonatal outcomes between two groups of patients showed meaningful benefits of progesterone in increasing of neonatal weight, reduction of low birth weight babies, and lowing neonate admitted in NICU. PMID:22685670

  14. Outcome of Vaginal Progesterone as a Tocolytic Agent: Randomized Clinical Trial

    PubMed Central

    Saleh Gargari, Soraya; Habibolahi, Malihe; Zonobi, Zahra; Khani, Zahra; Sarfjoo, Fatemeh Sadat; Kazemi Robati, Atefeh; Etemad, Roja; Karimi, Zohreh

    2012-01-01

    Vaginal progesterone has a potential beneficial effect in postponing of preterm labor by suppression of prostaglandins cascades. Although different studies evaluated the use of progesterone for preterm birth, the exact effect of which on prolongation of pregnancy remains unclear. Seventy two women who underwent preterm labor were managed by magnesium sulfate. Then they were randomly assigned to continue pregnancy either by applying vaginal progesterone (400 mg) until delivery or without using any drug. Gestational age mean at the time of delivery (P = 0.039) and postponing delivery mean time (P = 0.048) were significantly higher in progesterone group. Comparison of neonatal outcomes between two groups of patients showed meaningful benefits of progesterone in increasing of neonatal weight, reduction of low birth weight babies, and lowing neonate admitted in NICU. PMID:22685670

  15. Homeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone.

    PubMed

    Lessey, Bruce A; Young, Steven L

    2014-09-01

    Embryo implantation is regulated by an inflammatory process in response to sequential exposure to estrogen and progesterone, followed by resolution and repair. The actions of estrogen and progesterone on these inflammatory processes are tightly and reciprocally controlled through regulated expression of steroid receptors, cofactors, chaperone proteins, and downstream signaling components. In endometriosis, the inflammatory cascades, normally seen at menstruation, are prematurely activated and endogenous endometrial mechanisms of inflammation resolution appear defective. The temporally abnormally inflammation is also associated with an imbalance between estrogen and progesterone actions; the normal luteal-phase dominance of progesterone action appears to be lost and is replaced by progesterone resistance and estrogen dominance. In this review, we examine these relationships in greater detail and argue that estrogen action is a prime target for future therapeutic solutions to endometriosis and implantation failure that result from this chronic, inflammatory disease. PMID:24959818

  16. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone.

    PubMed

    Miller, Melissa R; Mannowetz, Nadja; Iavarone, Anthony T; Safavi, Rojin; Gracheva, Elena O; Smith, James F; Hill, Rose Z; Bautista, Diana M; Kirichok, Yuriy; Lishko, Polina V

    2016-04-29

    Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization. PMID:26989199

  17. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone.

    PubMed

    Miller, Melissa R; Mannowetz, Nadja; Iavarone, Anthony T; Safavi, Rojin; Gracheva, Elena O; Smith, James F; Hill, Rose Z; Bautista, Diana M; Kirichok, Yuriy; Lishko, Polina V

    2016-04-29

    Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization.

  18. An analysis of the binding of the chick oviduct progesterone-receptor to chromatin.

    PubMed

    Jaffe, R C; Socher, S H; O'Malley, B W

    1975-08-13

    The binding of progesterone-receptor complexes to chromatin from target and nontarget tissues was studied in vitro. Chromatin from both target and nontarget tissues responds in a similar manner to saly and cofactors and has the same K(D) (approx. 3.10(-9) M) for the progesterone-receptor complex. The only observed difference in the binding of the progesterone-receptor complex to target and nontarget chromatins is the difference in total number of acceptor sites. oviduct chromatin has approx. 1300 sites/pg DNA, spleen chromatin has approx. 840 sites/pg DNA, and erythrocyte chromatin has about 330 sites/pg DNA. The K(D) and number of acceptor sites for progesterone-receptor complex binding to oviduct chromatin remains the same even after extensive purification of the progesterone-receptor complex. Activation of cytosol labeled with [3H]progesterone by preincubation at 25 degrees C, analogous to that required for maximal nuclear binding, occurs if the binding studies to chromatin are performed in 0.025 M salt. The absence of an observable temperature effect when the studies are performed at 0.15 M salt is due to the activation of the receptor by salt. The dissociation of the progesterone-receptor complex from chromatin exhibits a single dissociation rate and the initial event is the appearance of free progesterone rather than a progesterone-receptor complex. Lastly, the treatment of chromatin with an antibody prepared against either single-stranded DNA or double-stranded DNA does not alter the extent of binding of the progesterone-receptor complex. Similarly, pretreatment of chromatin with a single-stranded nuclease does not inhibit the capacity of chromatin to bind the hormone-receptor complex.

  19. Disturbances in production of progesterone and their implications in plant studies.

    PubMed

    Janeczko, Anna; Oklestkova, Jana; Novak, Ondrej; Śniegowska-Świerk, Katarzyna; Snaczke, Zuzanna; Pociecha, Ewa

    2015-04-01

    Progesterone is a mammalian hormone that has also been discovered in plants but its physiological function in plants is not explained. Experiments using inhibitors of progesterone synthesis and binding would be useful in studies on the significance of this compound in plants. Until now, trilostane and mifepristone have been used in medical sciences as progesterone biosynthesis and binding inhibitors, respectively. We tested these synthetic steroids for the first time in plants and found that they reduced the content of progesterone in wheat. The aim of further experiments was to answer whether the potential disturbances in the production/binding of progesterone, influence resistance to environmental stress (drought) and the development of wheat. Inhibitors and progesterone were applied to plants via roots in a concentration of 0.25-0.5mg/l water. Both inhibitors lowered the activity of CO2 binding enzyme (Rubisco) in wheat exposed to drought stress and trilostane additionally lowered the chlorophyll content. However, trilostane-treated plants were rescued by treatment with exogenous progesterone. The inhibitors also modulated the development of winter wheat, which indicated the significance of steroid regulators and their receptors in this process. In this study, in addition to progesterone and its inhibitors, brassinosteroid (24-epibrassinolide) and an inhibitor of biosynthesis of brassinosteroids were also applied. Mifepristone inhibited the generative development of wheat (like 24-epibrassinolide), while trilostane (like progesterone and an inhibitor of biosynthesis of brassinosteroids) stimulated the development. We propose a model of steroid-induced regulation of the development of winter wheat, where brassinosteroids act as inhibitors of generative development, while progesterone or other pregnane derivatives act as stimulators.

  20. Persistent Genital Hyperinnervation Following Progesterone Administration to Adolescent Female Rats1

    PubMed Central

    Liao, Zhaohui; Smith, Peter G.

    2014-01-01

    ABSTRACT Provoked vestibulodynia, a female pelvic pain syndrome affecting substantial numbers of women, is characterized by genital hypersensitivity and sensory hyperinnervation. Previous studies have shown that the risk of developing provoked vestibulodynia is markedly elevated following adolescent use of oral contraceptives with high progesterone content. We hypothesized that progesterone, a steroid hormone with known neurotropic properties, may alter genital innervation through direct or indirect actions. Female Sprague Dawley rats received progesterone (20 mg/kg subcutaneously) from Days 20–27; tissue was removed for analysis in some rats on Day 28, while others were ovariectomized on Day 43 and infused for 7 days with vehicle or 17beta estradiol. Progesterone resulted in overall increases in vaginal innervation at both Day 28 and 50 due to proliferation of peptidergic sensory and sympathetic (but not parasympathetic) axons. Estradiol reduced innervation in progesterone-treated and untreated groups. To assess the mechanisms of sensory hyperinnervation, we cultured dissociated dorsal root ganglion neurons and found that progesterone increases neurite outgrowth by small unmyelinated (but not myelinated) sensory neurons, it was receptor mediated, and it was nonadditive with NGF. Pretreatment of ganglion with progesterone also increased neurite outgrowth in response to vaginal target explants. However, pretreatment of vaginal target with progesterone did not improve outgrowth. We conclude that adolescent progesterone exposure may contribute to provoked vestibulodynia by eliciting persistent genital hyperinnervation via a direct effect on unmyelinated sensory nociceptor neurons and that estradiol, a well-documented therapeutic, may alleviate symptoms in part by reducing progesterone-induced sensory hyperinnervation. PMID:25359899

  1. WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell proliferation

    PubMed Central

    Talbott, Alex; Bhusri, Anuradha; Krumsick, Zach; Foster, Sierra; Wormington, Joshua; Kimler, Bruce F

    2016-01-01

    Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3β (GSK-3β) and stimulating β-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidate Wnt genes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg/daily) rats, and progesterone-pretreated rats given a single dose (0.2µg) of estradiol. The spatial distribution of the WNT proteins was determined in the uteri after the same treatments. Wnt5a increased in response to progesterone and the protein emerged in the periluminal stromal cells of progesterone-pretreated rat uteri. To investigate whether WNT5A was required for proliferation, uterine stromal cell lines were stimulated with progesterone (1µM) and fibroblast growth factor (FGF, 50ng/mL). Proliferating stromal cells expressed a two-fold increase in WNT5A protein at 12h post stimulation. Stimulated stromal cells were cultured with actinomycin D (25µg/mL) to inhibit new RNA synthesis. Relative Wnt5a expression increased at 4 and 6 h of culture, suggesting that progesterone plus FGF preferentially increased Wnt5a mRNA stability. Knockdown of Wnt5a in uterine stromal cell lines inhibited stromal cell proliferation and decreased Wnt5a mRNA. The results indicate that progesterone initiates and synchronizes uterine stromal cell proliferation by increasing WNT5A expression and signaling. PMID:26975616

  2. The effect of progesterone on systemic inflammation and oxidative stress in the rat model of sepsis

    PubMed Central

    Aksoy, Ayse Nur; Toker, Aysun; Celık, Muhammet; Aksoy, Mehmet; Halıcı, Zekai; Aksoy, Hulya

    2014-01-01

    Objectives: To explore the protective effect of progesterone on inflammation and oxidative stress in a rat model of sepsis created by cecal ligation and puncture (CLP). Materials and Methods: Rats were randomly divided into 4 groups: Overiectomy group (OVX), sham operated (control), sepsis (CLP) group and progesterone-treated CLP group (CLP+ progesterone). The rats in CLP+ progesterone group received intraperitoneal progesterone (2 mg/kg). Cardiac blood samples were obtained for the measurement levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Tissue samples, including liver, kidney and uterus of rats were prepared to determine activities of myeloperoxidase (MPO), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). Results: Increased serum IL-6 and TNF-α levels were found in the CLP group in comparison with the control group (P = 0.01, P = 0.02; respectively). In CLP+ progesterone group, mean MDA concentration of kidney tissue was significantly lower than in CLP group (P = 0.003). Liver MDA concentration of the CLP+ progesterone group was not significantly different from that of the control group. While there were no significant differences among groups regarding liver MPO; in the CLP group, MPO activity in kidney (P = 0.02) and uterine tissues (P = 0.03) were found to be significantly higher compared to the control group. In CLP+ progesterone group, mean MPO activities of all tissues were not different than those of control group. The uterine tissue GPx activity in the CLP+ progesterone group was not statistically significantly different from control group. Conclusions: We suggest that progesterone ameliorates sepsis syndrome by reduction of the inflammatory cytokines IL-6 and TNF-α, and by restoration of antioxidant enzyme activities in some tissues. PMID:25538334

  3. Effect of progesterone pretreatment on cadmium toxicity in the male Fischer (F344/NCr) rat.

    PubMed

    Shiraishi, N; Barter, R A; Uno, H; Waalkes, M P

    1993-01-01

    A previous report has indicated that progesterone pretreatment can markedly reduce cadmium toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) rats. A single sc injection of 20 mumol CdCl2/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. However, when rats were pretreated with progesterone (100 mg/kg, sc, -48, -24, and 0 hr) and then given cadmium (20 mumol CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing a 53% mortality. Progesterone pretreatment had no effect on cadmium-induced testicular lesions in surviving rats. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated rats given cadmium as compared to rats given cadmium alone. Progesterone pretreatment had no effect on the distribution of cadmium to liver, kidney, or testes. Progesterone pretreatment also had no effect on the cadmium-induced increases in hepatic or renal metallothionein (MT) or hepatic or testicular MT mRNA levels. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated rats were doubled. These results indicate that, contrary to previously reported data for the mouse, progesterone pretreatment increased the lethality of cadmium in male Fischer (F344/NCr) rats and had no effect on cadmium-induced testicular toxicity. The mechanism by which progesterone enhanced cadmium toxicity, especially cadmium-induced hepatotoxicity, deserves further study. PMID:8430418

  4. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress.

    PubMed

    Janeczko, Anna; Oklešťková, Jana; Siwek, Agata; Dziurka, Michał; Pociecha, Ewa; Kocurek, Maciej; Novák, Ondřej

    2013-11-01

    Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35-46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in

  5. Novel anticonvulsive effects of progesterone in a mouse model of hippocampal electrical kindling.

    PubMed

    Jeffrey, M; Lang, M; Gane, J; Chow, E; Wu, C; Zhang, L

    2014-01-17

    Progesterone is a known anticonvulsant, with its inhibitory effects generally attributed to its secondary metabolite, 5α,3α-tetrahydroprogesterone (THP), and THP's enhancement of GABAA receptor activity. Accumulating evidence, however, suggests that progesterone may have non-genomic actions independent of the GABAA receptor. In this study, we explored THP/GABAA-independent anticonvulsive actions of progesterone in a mouse model of hippocampal kindling and in mouse entorhinal slices in vitro. Specifically, we examined the effects of progesterone in kindled mice with or without pretreatments with finasteride, a 5α-reductase inhibitor known to block the metabolism of progesterone to THP. In addition, we examined the effects of progesterone on entorhinal epileptiform potentials in the presence of a GABAA receptor antagonist picrotoxin and finasteride. Adult male mice were kindled via a daily stimulation protocol. Electroencephalographic (EEG) discharges were recorded from the hippocampus or cortex to assess "focal" or "generalized" seizure activity. Kindled mice were treated with intra-peritoneal injections of progesterone (10, 35, 100 and 160mg/kg) with or without finasteride pretreatment (50 or 100mg/kg), THP (1, 3.5, 10 and 30mg/kg), midazolam (2mg/kg) and carbamazepine (50mg/kg). Entorhinal cortical slices were prepared from naïve young mice, and repetitive epileptiform potentials were induced by 4-aminopyridine (100μM), picrotoxin (100μM) and finasteride (1μM). Pretreatment with finasteride did not abolish the anticonvulsant effects of progesterone. In finasteride-pretreated mice, progesterone at 100 and 160mg/kg decreased cortical but not hippocampal afterdischarges (ADs). Carbamazepine mimicked the effects of progesterone with finasteride pretreatments in decreasing cortical discharges and motor seizures, whereas midazolam produced effects similar to progesterone alone or THP in decreasing hippocampal ADs and motor seizures. In brain slices, progesterone

  6. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress.

    PubMed

    Janeczko, Anna; Oklešťková, Jana; Siwek, Agata; Dziurka, Michał; Pociecha, Ewa; Kocurek, Maciej; Novák, Ondřej

    2013-11-01

    Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35-46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in

  7. The effects of intra-dorsal hippocampus infusion of pregnenolone sulfate on memory function and hippocampal BDNF mRNA expression of biliary cirrhosis-induced memory impairment in rats.

    PubMed

    Dastgheib, M; Dehpour, A R; Heidari, M; Moezi, L

    2015-10-15

    Learning and memory impairment is one of the most challenging complications of cirrhosis and present treatments are unsatisfactory. The exact mechanism of cirrhosis cognitive dysfunction is unknown. Pregnenolone sulfate (PREGS) is an excitatory neurosteroid that acts as a N-methyl-D-aspartate (NMDA) receptor agonist and GABAA receptor antagonist. In this study we evaluated the effect of intra CA1 infusion of PREGS on cirrhotic rats' memory function using the Y-maze test. Hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression was also evaluated. Three weeks after bile duct ligation (BDL) surgery, rats were under stereotaxic surgery for insertion of two guide cannulas in the CA1 region of the hippocampus. After 1-week of recovery, PREGS was administered through CA1 cannulas in cirrhotic rats, while control or sham groups received vehicle. For evaluation of NMDA receptor role in memory-enhancing effects of PREGS, DL-2-Amino-5-phosphonopentanoic acid (AP5) which is a potent and competitive antagonist of NMDA receptor, co-administered with PREGS and for assessment of hippocampal BDNF mRNA expression, quantitative Real-time reverse transcriptase-PCR (RT-PCR) was used. Results showed that 28 days after BDL, cirrhotic animals' memory significantly decreased in comparison with control and sham groups, while PREGS infusion could restore memory impairment (P<0.05). PREGS effects on memory of cirrhotic rats were antagonized by DAP5. RT-PCR findings have shown that hippocampal relative BDNF mRNA expression was up-regulated in PREGS-treated groups in comparison with the BDL group (P<0.001). Our findings suggest that PREGS has a memory-enhancing effect in cirrhosis memory deficit in acute therapy and this effect may be through NMDA (glutamate) receptor involvement and BDNF mRNA expression.

  8. The impact of progesterone supplementation on pregnancy rates after intrauterine insemination in patients developing a single follicle.

    PubMed

    Güven, Davut; Batıoğlu, Ali; Sari, Seher; Bakay, Kadir

    2016-06-01

    The objective was to determine whether progesterone support affects pregnancy rates in patients who develop a single follicle. This was a non-randomized prospective controlled study performed on 591 intrauterine insemination (IUI) cycles that developed a single follicle; 337 women received 100 mg oral progesterone daily. The pregnancy rate was 24.3%, or 82 out of 337, in the group receiving progesterone support compared with 14.96%, or 254 out of 591, in the group with no progesterone support. IUI luteal phase supplementation with oral progesterone may improve clinical pregnancy rates when begun the day after insemination. PMID:27321474

  9. Studies of conformation and interaction of the cyclohexenone and acetyl group of progesterone with liposomes.

    PubMed

    Sanchez-Bueno, A; Watanabe, S; Sancho, M J; Saito, T

    1991-02-01

    The conformations of the A-ring and the 17-acetyl groups of progesterone were examined within liposomes, which were prepared from L-alpha-phosphatidylcholine in the presence or absence of cholesterol in the buffer, using qualitative nuclear magnetic resonance and circular dichroism of the progesterone spectra in the wavelength regions of 260-360 nm. The preferred conformational assignments, in the rotational conformations of the 17-acetyl group and invertible conformations of the cyclohexenone of progesterone were discussed on the basis of the elliptical strength of the Cotton effect and an energy estimation of the preferred conformers. Energetically unstable conformers of the acetyl group and alpha,beta-unsaturated cyclohexenone of progesterone remarkably increased with an increase in the concentration of the liposomes. The liposomes containing 10% cholesterol were similar to the effect of the liposomes lacking cholesterol on the 17-acetyl group and the alpha,beta-unsaturated cyclohexenone but those containing 50% cholesterol showed an increase in the number of energetically stable conformers of the alpha,beta-unsaturated cyclohexenone. The nuclear magnetic resonance signal from liposomes together with the progesterone indicated the existence of the progesterone adjacent to a double bond or ester moiety in the lipid molecule. Therefore, it was apparent that the liposomes and the cholesterol within the liposomes regulated the conformational populations of both the cyclohexone and acetyl groups of the progesterone molecule. PMID:2004040

  10. Progesterone stimulates respiration through a central nervous system steroid receptor-mediated mechanism in cat.

    PubMed

    Bayliss, D A; Millhorn, D E; Gallman, E A; Cidlowski, J A

    1987-11-01

    We have examined the effect on respiration of the steroid hormone progesterone, administered either intravenously or directly into the medulla oblongata in anesthetized and paralyzed male and female cats. The carotid sinus and vagus nerves were cut, and end-tidal PCO2 and temperature were kept constant with servo-controllers. Phrenic nerve activity was used to quantitate central respiratory activity. Repeated doses of progesterone (from 0.1 to 2.0 micrograms/kg, cumulative) caused a sustained (greater than 45 min) facilitation of phrenic nerve activity in female and male cats; however, the response was much more variable in females. Progesterone injected into the region of nucleus tractus solitarii, a respiratory-related area in the medulla oblongata, also caused a prolonged stimulation of respiration. Progesterone administration at high concentration by both routes also caused a substantial hypotension. Identical i.v. doses of other classes of steroid hormones (17 beta-estradiol, testosterone, and cortisol) did not elicit the same respiratory effect. Pretreatment with RU 486, a progesterone-receptor antagonist, blocked the facilitatory effect of progesterone. We conclude that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration. PMID:3478727

  11. Plasma progesterone levels in the pregnant female rat-kangaroo (Bettongia gaimardi).

    PubMed

    Jones, S M; Rose, R W

    1992-08-01

    Plasma progesterone levels were measured in female bettongs (small macropodid marsupials) under two natural regimes: (1) during "delayed" gestation (initiated by removal of pouch young, RPY) and (2) during the pregnancy prior to pouch vacation when a young still occupies the pouch (i.e., during lactation). Basal levels of progesterone were 0.15-0.5 ng/ml. There was a transient peak of progesterone (0.7 ng/ml) early in gestation at Day 4 RPY. After Day 6 RPY, progesterone levels remained elevated (1.2-1.5 ng/ml) until they dropped sharply to basal levels on the day of birth. This pattern of progesterone secretion during delayed gestation is similar to that seen in other marsupials, such as the tammar wallaby. There was no significant difference between the progesterone profiles of the two experimental groups. We deduce, then, that lactation had no effect on corpus luteum function (as assessed by plasma progesterone levels) in the pregnant bettong.

  12. Progesterone and its downstream molecules as blastocyst implantation essential factors.

    PubMed

    Yoshinaga, Koji

    2014-08-01

    This review is to update the previous review (Am J Reprod Immunol, 63, 2010 and 413) on the research on blastocyst implantation essential factors (BIEFs). Focus of the current review is on progesterone and its downstream molecules in the process of blastocyst implantation. To understand the process of implantation, we need to know where and when the BIEFs are expressed and what they do. Progress in this research area is rapid, and its update is indeed necessary. The basic concept of BIEFs is that they have dual functions, one physiological and the other immunological (J Reprod Dev, 58, 2012 and 196). As we are still exploring the mechanism of implantation, available data are incomplete and human data are few. Thus, I will use information obtained through research on animal models, in vitro studies, cell lines, and some human studies where available. The ultimate goal of the review is to understand human blastocyst implantation. PMID:24754263

  13. Progesterone Regulates Secretin Expression in Mouse Uterus During Early Pregnancy

    PubMed Central

    Huang, Zhu; Wang, Tong-Song; Qi, Qian-Rong; Zuo, Ru-Juan; Liang, Xiao-Huan; Zhao, Xu-Yu

    2014-01-01

    Secretin, a classical gastrointestinal and neuroendocrine peptide, plays an important role in maintaining the body fluid balance. However, the expression and regulation of secretin in the reproductive system are still unknown. In our study, secretin is specifically expressed in the decidua on days 5 to 8 of pregnancy. Secretin expression is not detected under delayed implantation but is stimulated after estrogen activation and under artificial decidualization. Progesterone induces secretin expression in ovariectomized mice and cultured stromal cells, which is abrogated by specific LY294002. Because secretin is mainly localized in the decidua and also strongly expressed during in vitro decidualization, secretin may play a role during mouse decidualization through regulating cyclic adenosine monophosphate level. PMID:24336673

  14. Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats.

    PubMed

    Karim, Kamarulzaman; Giribabu, Nelli; Muniandy, Sekaran; Salleh, Naguib

    2016-04-01

    We hypothesized that progesterone-induced decrease in uterine fluid pH involves V-ATPase. In this study, expression and functional activity of V-ATPase in uterus were investigated under progesterone influence. Ovariectomized adult female rats received subcutaneous injection of estradiol-17β (1 µg/kg/day) or progesterone (20 mg/kg/day) for 3 days or 3 days estradiol-17β followed by 3 days vehicle, progesterone, or estradiol-17β plus progesterone. Mifepristone, a progesterone receptor blocker, was concomitantly given to the rats which received progesterone. A day after last injection, rate of uterine fluid secretion, its HCO3 (-) concentration, and pH were determined via in vivo uterine perfusion in rats under anesthesia. V-ATPase inhibitor, bafilomycin, was introduced into the perfusion buffer, and changes in these parameters were observed. Expression of V-ATPase A1 and B1/2 proteins and mRNAs in uterus were quantified by Western blotting and real-time PCR, respectively. Distribution of these proteins was observed by immunohistochemistry. Our findings showed that under progesterone influence, uterine fluid secretion rate, HCO3 (-) concentration, and pH were significantly reduced. Administration of bafilomycin did not cause significant changes in fluid secretion rate; however, HCO3 (-) concentration and pH were significantly elevated. In parallel with these changes, expression of V-ATPase A1 and B1/2 proteins and mRNAs were significantly increased with these proteins highly distributed in uterine luminal and glandular epithelia. In conclusion, increased expression and functional activity of V-ATPase were most likely responsible for the decreased in uterine fluid pH observed under progesterone influence.

  15. The biology of progesterone receptor in the normal mammary gland and in breast cancer.

    PubMed

    Obr, Alison E; Edwards, Dean P

    2012-06-24

    This paper reviews work on progesterone and the progesterone receptor (PR) in the mouse mammary gland that has been used extensively as an experimental model. Studies have led to the concept that progesterone controls proliferation and morphogenesis of the luminal epithelium in a tightly orchestrated manner at distinct stages of development by paracrine signaling pathways, including receptor activator of nuclear factor κB ligand (RANKL) as a major paracrine factor. Progesterone also drives expansion of stem cells by paracrine signals to generate progenitors required for alveologenesis. During mid-to-late pregnancy, progesterone has another role to suppress secretory activation until parturition mediated in part by crosstalk between PR and prolactin/Stat5 signaling to inhibit induction of milk protein gene expression, and by inhibiting tight junction closure. In models of hormone-dependent mouse mammary tumors, the progesterone/PR signaling axis enhances pre-neoplastic progression by a switch from a paracrine to an autocrine mode of proliferation and dysregulation of the RANKL signaling pathway. Limited experiments with normal human breast show that progesterone/PR signaling also stimulates epithelial cell proliferation by a paracrine mechanism; however, the signaling pathways and whether RANKL is a major mediator remains unknown. Work with human breast cancer cell lines, patient tumor samples and clinical studies indicates that progesterone is a risk factor for breast cancer and that alteration in progesterone/PR signaling pathways contributes to early stage human breast cancer progression. However, loss of PR expression in primary tumors is associated with a less differentiated more invasive phenotype and worse prognosis, suggesting that PR may limit later stages of tumor progression.

  16. Progesterone promotes survival of the rat corpus luteum in the absence of cognate receptors.

    PubMed

    Goyeneche, Alicia A; Deis, Ricardo P; Gibori, Geula; Telleria, Carlos M

    2003-01-01

    Progesterone production by the corpus luteum (CL) is essential for preparation of the endometrium for implantation and for the maintenance of gestation. Progesterone modulates its own production and opposes functional luteal regression induced by exogenous agents, such as prostaglandin F(2alpha). In the present study, we evaluated whether progesterone is also capable of interfering with the process of structural luteal regression, which is characterized by a decrease in weight and size of the gland because of programmed cell death (i.e., apoptosis). We have found that a low number of luteal cells undergo apoptosis throughout gestation. On the day of parturition, but following the initial decline in endogenous progesterone production, a small increase in the number of luteal cells undergoing cell death was observed. This increase in apoptotic cells continued postpartum, reaching dramatic levels by Day 4 postpartum, and was accompanied by a marked decrease in average luteal weight. We have established that the exogenous administration of progesterone significantly reduces the decline in luteal weight observed during structural luteal regression postpartum. This effect was associated with a decrease in the number of cells undergoing apoptosis and with enhanced circulating levels of androstenedione. Furthermore, in vivo administration of progesterone delayed the occurrence of DNA fragmentation in postpartum CL incubated in serum-free conditions. Finally, we have shown that neither the CL of gestation nor the newly formed CL after postpartum ovulation express the classic progesterone-receptor mRNA. In summary, the present results support a protective action of progesterone on the function and survival of the CL through inhibition of apoptosis and stimulation of androstenedione production. Furthermore, this effect is carried out in the absence of classic progesterone receptors.

  17. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study

    PubMed Central

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G.

    2014-01-01

    Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

  18. Central neural mechanisms of progesterone action: application to the respiratory system.

    PubMed

    Bayliss, D A; Millhorn, D E

    1992-08-01

    Around the turn of the century, it was recognized that women hyperventilate during the luteal phase of the menstrual cycle and during pregnancy. Although a causative role for the steroid hormone progesterone in this hyperventilation was suggested as early as the 1940s, there has been no clear indication as to the mechanism by which it produces its respiratory effects. In contrast, much mechanistic information has been obtained over the same period about a different effect of progesterone, i.e., the facilitation of reproductive behaviors. In this case, the bulk of the evidence supports the hypothesis that progesterone acts via a genomic mechanism with characteristics not unlike those predicted by classic models for steroid hormone action. We recently, therefore, undertook a series of experiments to test predictions of those same models with reference to the respiratory effects of progesterone. Here we highlight the results of those studies; as background to and precedent for our experiments, we briefly review previous work in which effects of progesterone on respiration and reproductive behaviors have been studied. Our results indicate that the respiratory response to progesterone is mediated at hypothalamic sites through an estrogen- (E2) dependent progesterone receptor- (PR) mediated mechanism requiring RNA and protein synthesis, i.e., gene expression. The E2 dependence of the respiratory response to progesterone is likely a consequence of the demonstrated induction of PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural mechanisms underlying the stimulation of respiration by progesterone were similar to those mediating its reproductive effects. PMID:1399957

  19. Vacuolar-ATPase (V-ATPase) Mediates Progesterone-Induced Uterine Fluid Acidification in Rats.

    PubMed

    Karim, Kamarulzaman; Giribabu, Nelli; Muniandy, Sekaran; Salleh, Naguib

    2016-04-01

    We hypothesized that progesterone-induced decrease in uterine fluid pH involves V-ATPase. In this study, expression and functional activity of V-ATPase in uterus were investigated under progesterone influence. Ovariectomized adult female rats received subcutaneous injection of estradiol-17β (1 µg/kg/day) or progesterone (20 mg/kg/day) for 3 days or 3 days estradiol-17β followed by 3 days vehicle, progesterone, or estradiol-17β plus progesterone. Mifepristone, a progesterone receptor blocker, was concomitantly given to the rats which received progesterone. A day after last injection, rate of uterine fluid secretion, its HCO3 (-) concentration, and pH were determined via in vivo uterine perfusion in rats under anesthesia. V-ATPase inhibitor, bafilomycin, was introduced into the perfusion buffer, and changes in these parameters were observed. Expression of V-ATPase A1 and B1/2 proteins and mRNAs in uterus were quantified by Western blotting and real-time PCR, respectively. Distribution of these proteins was observed by immunohistochemistry. Our findings showed that under progesterone influence, uterine fluid secretion rate, HCO3 (-) concentration, and pH were significantly reduced. Administration of bafilomycin did not cause significant changes in fluid secretion rate; however, HCO3 (-) concentration and pH were significantly elevated. In parallel with these changes, expression of V-ATPase A1 and B1/2 proteins and mRNAs were significantly increased with these proteins highly distributed in uterine luminal and glandular epithelia. In conclusion, increased expression and functional activity of V-ATPase were most likely responsible for the decreased in uterine fluid pH observed under progesterone influence. PMID:26403527

  20. Expression of estrogen and progesterone receptors in papillary thyroid carcinoma

    PubMed Central

    Jalali-Nadoushan, Mohammad-Reza; Amirtouri, Reza; Davati, Ali; Askari, Samaneh; Siadati, Sepideh

    2016-01-01

    Background: Papillary thyroid carcinoma (PTC), occurs mostly in women and sex hormones may play a role in the pathogenesis and clinical course. The objective of this study was to determine the status and prevalence of estrogen and progesterone receptors in PTC with regard to age, gender, tumor size and lymph node involvement. Methods: Immunohistochemical stains were performed on 92 tissue blocks of PTC for estrogen receptor (ER) and progesterone receptor (PR) expression in tumor cells. Chi-square test and Mann-Whitney U test were used to determine statistical difference using statistical software SPSS. Results: The mean age of patients was 39.32±1.7 years (range 13-80) with 79(85.9%) women and 13 (14.1%) men. Lymph node involvement was seen in 76.1% of patients. The average tumor size was 3.6±2.21 cm. The rate of ER and PR expression were 46.75% and 5.6%, respectively. ER expression for females was higher than males (P=0.014), but no relation was found between males and females in PR expression (P=0.7). Also there was no statistical difference between ER and PR expression with respect to age, lymph node involvement and tumor size. Conclusion: Our study showed higher ER expression in females than males with PTC. No relation was found between the expression of these receptors and age of presentation, lymph node involvement and tumor size. Further investigation is required to determine the prognostic importance of ER and PR in PTC.

  1. Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer

    PubMed Central

    Dai, Donghai; Meng, Xiangbing; Thiel, Kristina W.; Leslie, Kimberly K.; Yang, Shujie

    2016-01-01

    Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term “molecularly enhanced progestin therapy.” What remained unclear was the mechanism of action and if estrogen receptor α (ERα), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a

  2. The advantage of polymer addition to a non-ionic oil in water microemulsion for the dermal delivery of progesterone.

    PubMed

    Biruss, Babette; Valenta, Claudia

    2008-02-12

    The influence of progesterone on the physicochemical behaviour of the o/w microemulsion consisting of the non-ionic surfactant polyoxyethylene-10-dodecyl ether, tributyrin and water was investigated. Thereby no significant influence could be detected in terms of droplet size, zeta potential, conductivity and pH by progesterone. However the chemical stability of progesterone was insufficient during the storage of 6 months. Therefore, two different polymeric agents, named silicon dioxide and polymeric emulsifier, were added to the progesterone containing microemulsions. These polymers increased the chemical stability of progesterone significantly. Moreover the polymeric additives improved the skin permeation 1.24- and 1.63-fold and decreased the skin retention in relation to the pure microemulsion. The polymer-stabilized progesterone microemulsions are interesting vehicles for skin application of progesterone. PMID:17869457

  3. A Functional Relay from Progesterone to Vitamin D in the Immune System

    PubMed Central

    2015-01-01

    Progesterone is a steroid hormone that promotes and maintains pregnancy. Vitamin D (vit. D), another steroid hormone, regulates calcium levels and bone health among many of its functions. The two hormones play important roles also in regulating the immune system. Recently, we discovered that the vitamin D receptor (VDR) is induced in T cells by progesterone. This finding connects the function of progesterone to that of vit. D and suggests that the two steroid hormones cooperate with each other for sequential and effective regulation of the immune system. Potential implications of the regulation in health and disease are discussed. PMID:25826095

  4. Estrus synchronization and fertility behavior in Black Bengal goats following either progesterone or prostaglandin treatment.

    PubMed

    Ishwar, A K; Pandey, J N

    1990-11-01

    Thirty-six Black Bengal female goats were in the study. They were divided into three groups of 12 goats each. Group I served as the control, Group II was treated with progesterone, Group III was administered prostaglandin F2alpha. There was 100% estrus synchronization in the PGF2alpha treated group and 90% in the progesterone treated group. The total number of kids produced in the PGF2 alpha treated group was 15 followed by 12 in the progesterone - treated group and 6 in the control group. The gestation length was found to be similar in all three groups. PMID:16726900

  5. Serum progesterone determination as an aid for pregnancy diagnosis in goats bred out of season.

    PubMed

    Fleming, S A; Van Camp, S D; Chapin, H M

    1990-02-01

    Nubian does (n = 12) were bred by artificial insemination after induction of estrus with medroxyprogesterone acetate impregnated vaginal sponges and pregnant mare serum gonadotrophin injections during the anestrous season. Pregnancy status was predicted from serum samples collected 21 days following the last breeding and analyzed using 1) a commercial bovine milk progesterone enzyme immunoassay test (EIA), and 2) a radioimmunoassay progesterone (RIA) test. Both tests detected nonpregnancy (EIA 100%, RIA 80%) more accurately than pregnancy (EIA 66%, RIA 75%). Commercial bovine progesterone EIA kits have potential as rapid, inexpensive screening tests for nonpregnant does bred out of season. PMID:17423508

  6. Serum progesterone determination as an aid for pregnancy diagnosis in goats bred out of season

    PubMed Central

    Fleming, Sherrill A.; Van Camp, Steven D.; Chapin, Heath M.

    1990-01-01

    Nubian does (n = 12) were bred by artificial insemination after induction of estrus with medroxyprogesterone acetate impregnated vaginal sponges and pregnant mare serum gonadotrophin injections during the anestrous season. Pregnancy status was predicted from serum samples collected 21 days following the last breeding and analyzed using 1) a commercial bovine milk progesterone enzyme immunoassay test (EIA), and 2) a radioimmunoassay progesterone (RIA) test. Both tests detected nonpregnancy (EIA 100%, RIA 80%) more accurately than pregnancy (EIA 66%, RIA 75%). Commercial bovine progesterone EIA kits have potential as rapid, inexpensive screening tests for nonpregnant does bred out of season. PMID:17423508

  7. A functional relay from progesterone to vitamin D in the immune system.

    PubMed

    Kim, Chang H

    2015-06-01

    Progesterone is a steroid hormone that promotes and maintains pregnancy. Vitamin D (vit. D), another steroid hormone, regulates calcium levels and bone health among many of its functions. The two hormones play important roles also in regulating the immune system. Recently, we discovered that the vitamin D receptor (VDR) is induced in T cells by progesterone. This finding connects the function of progesterone to that of vit. D and suggests that the two steroid hormones cooperate with each other for sequential and effective regulation of the immune system. Potential implications of the regulation in health and disease are discussed. PMID:25826095

  8. Oestrus expression and ovarian function in repeat breeder cows, monitored by ultrasonography and progesterone assay.

    PubMed

    Pérez-Marín, C C; España, F

    2007-10-01

    Ovarian ultrasonography and plasma progesterone levels were monitored in 37 lactating Holstein cows with a history of repeat breeding; the data obtained were analysed in conjunction with clinical and behavioural signs, to identify the aetiology of the syndrome. Differences were detected between RBCs displaying apparently normal cycles and others with irregular cycles. There were also differences in heat expression; a large number of repeat breeder cows (RBCs, 50%) displayed delayed or silent oestrus. Ovarian disorders were common in RBCs, and included ovarian cysts, mistimed AI, subluteal progesterone levels, luteal dysfunction or ovulation defects. Both ultrasonography and plasma progesterone assays are useful tools for ascertaining the aetiology of the repeat breeder syndrome. PMID:17845598

  9. Use of plasma progesterone profiles for the assessment of reproductive functions in indigenous Nigerian Zebu cattle.

    PubMed

    Oyedipe, E O; Pathiraja, N; Voh, A A; Buvanendran, V

    1988-09-01

    The reproductive performance of Zebu cattle is generally low. However, blood concentrations of progesterone may be of practical value in assessing the reproductive status of the Zebu female. This paper reviews recent findings regarding plasma progesterone profiles during different phases of the reproductive cycle of some Nigerian Zebu cattle. The reproductive phases examined include the estrous cycle, early pregnancy and the postpartum periods. Our findings describe variations in plasma progesterone profiles observed under field conditions. The practical implications of these findings in assessing reproductive functions in indigenous Nigerian Zebu cattle are examined. PMID:16726505

  10. Oestrus expression and ovarian function in repeat breeder cows, monitored by ultrasonography and progesterone assay.

    PubMed

    Pérez-Marín, C C; España, F

    2007-10-01

    Ovarian ultrasonography and plasma progesterone levels were monitored in 37 lactating Holstein cows with a history of repeat breeding; the data obtained were analysed in conjunction with clinical and behavioural signs, to identify the aetiology of the syndrome. Differences were detected between RBCs displaying apparently normal cycles and others with irregular cycles. There were also differences in heat expression; a large number of repeat breeder cows (RBCs, 50%) displayed delayed or silent oestrus. Ovarian disorders were common in RBCs, and included ovarian cysts, mistimed AI, subluteal progesterone levels, luteal dysfunction or ovulation defects. Both ultrasonography and plasma progesterone assays are useful tools for ascertaining the aetiology of the repeat breeder syndrome.

  11. An earlier rise in systemic progesterone and increased progesterone in the uterine vein during early pregnancy are associated with enhanced embryonic survival in the ewe.

    PubMed

    O'Connell, Anne R; Hurst, Peter R; Davis, George H; McNatty, Kenneth P; Taylor, Sarah L; Juengel, Jennifer L

    2013-08-01

    Improved livestock production efficiency through greater embryonic survival (ES) is of economic and animal welfare benefit. Physiological characterization of animals that are extreme outliers for ES provides a valuable opportunity to identify a naturally occurring mechanism by which this trait may be enhanced. The objective was to determine the likely cause for the lifetime history of enhanced or reduced ES in a line of ewes selected for high fecundity. To address this question, progesterone concentrations in peripheral plasma as well as ovarian and uterine venous plasma samples were compared between groups of ewes with a lifetime history of either enhanced or reduced ES. The ability of the uterus to synthesize progesterone de novo at Day 5 of gestation was also tested. Ewes with enhanced ES had an earlier rise in progesterone concentration after estrus, irrespective of pregnancy status. In addition, there were increased concentrations of progesterone in the uterine vein in enhanced ES compared with reduced ES ewes on Day 5 of gestation (8.3 ± 0.8 ng/mL and 3.9 ± 1.4 ng/mL, respectively, P < 0.05). However, there were no differences in ovarian venous plasma (enhanced ES, 1725 ± 166 ng/mL; reduced ES, 1665 ± 268 ng/mL) at Day 5 of gestation. Although the endometrial tissue of some ewes (3/8) at Day 5 of gestation expressed three of the key genes necessary for regulation of de novo synthesis of progesterone, expression was not present exclusively in either of the two ES groups and therefore was unlikely to explain differences in the uterine vein progesterone concentrations between the enhanced and reduced ES groups. Collectively, the earlier rise in progesterone concentrations in peripheral plasma during the first week of gestation in the enhanced ES animals was independent of the presence of an embryo. Moreover, increased progesterone concentrations were also observed in the uterine vein at Day 5 of gestation of the enhanced ES ewes. It is proposed that the

  12. Regulation of progesterone signaling during pregnancy: implications for the use of progestins for the prevention of preterm birth.

    PubMed

    Byrns, Michael C

    2014-01-01

    Preterm birth is a major cause of neonatal morbidity and mortality. Progesterone plays a critical role in suppressing the inflammatory signals that would induce parturition prior to term. Progesterone signaling is regulated in a variety of ways during pregnancy. Endocrine production of high levels of progesterone by the placenta ensures the availability of high levels of progesterone throughout pregnancy. Paracrine regulation of progesterone metabolism in target tissues, particularly the myometrium and cervix, also determines the amount of progesterone ligand available. Progesterone metabolism can also lead to the formation of metabolites that contribute to its effects. In particular, 5β-dihydroprogesterone formation by aldo-keto reductase 1D1 appears to play an important role in maintaining uterine quiescence. Progesterone signaling can also be regulated at the receptor level through changes in the relative expression of the nuclear progesterone receptor isoforms, reduced expression of membrane receptors, and changes in the expression levels of coactivators and/or corepressors, including nuclear factor κB. Progesterone and 17α-hydroxyprogesterone caproate (17OH-PC) have recently been shown to reduce preterm births in women with previous preterm birth or shortened cervix. It is important to realize that these two progestins are likely to act in significantly different ways, which will likely influence their efficacy. The structural differences and resistance to metabolism exhibited by 17OH-PC means that it will be unable to activate some of the pathways that progesterone activates, but that it also will not be subject to paracrine inactivation. The fact that progesterone therapy works for maintaining pregnancy in some women, indicates that for those women insufficient levels of progesterone ligand in target tissues is a determining factor in early parturition, despite high levels of circulating progesterone. This article is part of a Special Issue entitled

  13. Progesterone, follicular, and estrual responses to progesterone-based estrus and ovulation synchronization protocols at five stages of the estrous cycle.

    PubMed

    Stevenson, J S

    2008-12-01

    The objective was to monitor changes in ovarian status in heifers exposed to a progesterone insert with or without concurrent GnRH injection. Estrus was manipulated in 283 heifers (31 breeding clusters) by administering GnRH, progesterone, and PGF(2alpha) at 5 stages of the estrous cycle. Estrus was presynchronized with a progesterone insert (CIDR) for 7 d before PGF(2alpha) was administered 24 h before insert removal. Successive clusters of heifers were assigned to treatments (2 heifers per treatment) on cycle d 2, 5, 10, 15, and 18. Treatments consisted of a progesterone insert (d 0) for 7 d plus: 1) PGF(2alpha) on d 6, 24 h before insert removal (early PGF); 2) GnRH on d 0 + early PGF(2alpha) (GnRH + early PGF); 3) PGF(2alpha) at insert removal (late PGF); and 4) GnRH on d 0 + late PGF (GnRH + late PGF). Controls received GnRH on d 0 and PGF(2alpha) on d 7. Ovaries were scanned by transrectal ultrasonography on d 0, 2, 7, 9, and 11 to assess follicle diameters and ovulation. Blood was collected on d 0, 2, 6, 7, 8, and 9 to quantify serum concentrations of progesterone. Insemination occurred after detected estrus or by timed artificial insemination (TAI) at 64 h after insert removal. Only 25% of 141 GnRH-treated heifers ovulated by d 2; twice as many ovulated when treatment was initiated on d 5 (46.4%) than on other cycle days (20.3%). Diameters of the largest follicle exposed to GnRH on d 0, 2, 7, or 9 did not differ regardless of whether ovulation occurred. Small treatment and stage of cycle differences in diameter of the largest follicle were detected on d 2, 7, and 9. Compared with controls, progesterone concentration was greater in all progesterone-treated heifers on d 2 and 6. Early- vs. late-PGF treatment resulted in less progesterone on d 7 and 8. Pregnancies per AI were less after TAI (44%) than after detected estrus (56%) and were less in controls than in all progesterone treatments. Heifers in which treatments were initiated on d 10 of the cycle had

  14. Temporal association of serum progesterone concentrations and vaginal cytology in walruses (Odobenus rosmarus).

    PubMed

    Kinoshita, K; Kiwata, M; Kuwano, R; Sato, N; Tanaka, T; Nagata, M; Taira, H; Kusunoki, H

    2012-03-15

    Concentrations of serum estradiol-17β and progesterone were monitored in six female walruses using an enzyme immunoassay. Progesterone concentrations increased from March to May in females aged 6 y or older, and subsequently declined (October). No significant elevation of estradiol-17β concentration was detected before an elevation of progesterone concentration. Vaginal smears from four females were examined with Papanicolaou staining. In all females, most epithelial cells were basophilic intermediate-superficial cells; no color change from basophilic to eosinophilic of the cells was detected. Meanwhile, the percentage of anucleate cells in vaginal smears reached its highest value before the elevation of progesterone concentration, followed by an increase in the percentage of leukocytes. We inferred that the change in populations of anucleate cells and leukocytes in vaginal smears reflected ovarian status and CL formation in female walruses. PMID:22153266

  15. Progesterone receptor knockout mice have an improved glucose homeostasis secondary to -cell proliferation

    NASA Astrophysics Data System (ADS)

    Picard, Frédéric; Wanatabe, Mitsuhiro; Schoonjans, Kristina; Lydon, John; O'Malley, Bert W.; Auwerx, Johan

    2002-11-01

    Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female db/db mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and db/db mice. Furthermore, female, but not male, PR-/- mice had lower fasting glycemia than PR+/+ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-/- mice were larger and secreted more insulin consequent to an increase in -cell mass due to an increase in -cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.

  16. The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects

    PubMed Central

    Wei, Jing; Xiao, Guo-min

    2013-01-01

    Traumatic brain injury is the leading cause of morbidity and mortality in young adults. The secondary injury in traumatic brain injury consists of a complex cascade of processes that simultaneously react to the primary injury to the brain. This cascade has been the target of numerous therapeutic agents investigated over the last 30 years, but no neuroprotective treatment option is currently available that improve neurological outcome after traumatic brain injury. Progesterone has long been considered merely a female reproductive hormone. Numerous studies, however, show that progesterone has substantial pleiotropic properties as a neuroprotective agent in both animal models and humans. Here, we review the increasing evidence that progesterone can act as a neuroprotective agent to treat traumatic brain injury and the mechanisms underlying these effects. Additionally, we discuss the current progress of clinical studies on the application of progesterone in the treatment of traumatic brain injuries. PMID:24241345

  17. Temporal association of serum progesterone concentrations and vaginal cytology in walruses (Odobenus rosmarus).

    PubMed

    Kinoshita, K; Kiwata, M; Kuwano, R; Sato, N; Tanaka, T; Nagata, M; Taira, H; Kusunoki, H

    2012-03-15

    Concentrations of serum estradiol-17β and progesterone were monitored in six female walruses using an enzyme immunoassay. Progesterone concentrations increased from March to May in females aged 6 y or older, and subsequently declined (October). No significant elevation of estradiol-17β concentration was detected before an elevation of progesterone concentration. Vaginal smears from four females were examined with Papanicolaou staining. In all females, most epithelial cells were basophilic intermediate-superficial cells; no color change from basophilic to eosinophilic of the cells was detected. Meanwhile, the percentage of anucleate cells in vaginal smears reached its highest value before the elevation of progesterone concentration, followed by an increase in the percentage of leukocytes. We inferred that the change in populations of anucleate cells and leukocytes in vaginal smears reflected ovarian status and CL formation in female walruses.

  18. Cloning and initial characterization of nuclear and membrane progesterone receptors in the Fathead Minnow, Pimephales promelas

    EPA Science Inventory

    Both native progestagens and synthetic progestins have important effects on reproduction that are mediated through progesterone receptors (PRs). They regulate gamete maturation and can serve as precursors for other steroid hormones in vertebrates and act as reproductive pheromone...

  19. Interplay between progesterone and prolactin in mammary development and implications for breast cancer.

    PubMed

    Lee, Heather J; Ormandy, Christopher J

    2012-06-24

    Progesterone and prolactin remodel mammary morphology during pregnancy by acting on the mammary epithelial cell hierarchy. The roles of each hormone in mammary development have been well studied, but evidence of signalling cross-talk between progesterone and prolactin is still emerging. Factors such as receptor activator of NFkB ligand (RANKL) may integrate signals from both hormones to orchestrate their joint actions on the epithelial cell hierarchy. Common targets of progesterone and prolactin signalling are also likely to integrate their pro-proliferative actions in breast cancer. Therefore, a thorough understanding of the interplay between progesterone and prolactin in mammary development may reveal therapeutic targets for breast cancer. This review summarises our understanding of Pg and PRL action in mammary gland development before focusing on molecular mechanisms of signalling cross-talk and the implications for breast cancer.

  20. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    PubMed Central

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  1. Expression of estrogen and progesterone receptors in astrocytomas: a literature review.

    PubMed

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde-Junior, Airton Mendes; Barros-Oliveira, Maria da Conceição; Sousa, Emerson Brandão; Barros, Lorena da Rocha; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-08-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: "estrogen receptor beta" OR "estrogen receptor alpha" OR "estrogen receptor antagonists" OR "progesterone receptors" OR "astrocytoma" OR "glioma" OR "glioblastoma". Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  2. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    PubMed Central

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  3. Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus

    PubMed Central

    Nissenson, R.; Flouret, G.; Hechter, O.

    1978-01-01

    Estradiol-17β administration to young (10- to 12-week-old) rabbits to produce the “estrogen-dominated” uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In “progesterone-dominated” uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [3H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [3H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [3H]oxytocin binding; the concentration of specific [3H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon

  4. Determination of ovarian cyclicity and pregnancy using fecal progesterone in forest musk deer (Moschus berezovskii).

    PubMed

    Wang, Yi-Hua; Liu, Shu-Qiang; Yang, Shuang; Zhang, Tian-Xiang; Wei, Yu-Ting; Zhou, Jun-Tong; Hu, De-Fu; Li, Lin-Hai

    2016-07-01

    The forest musk deer (FMD, Moschus berezovskii) is a threatened species in China. Although crucial for its artificial breeding management and thus protection, to date, gonadal steroidogenic activity data are unavailable in this species. Thus, the objectives of the present study were to characterize ovarian activity throughout the estrous cycle, non-pregnant luteal phase, and gestation in female FMD. These goals were accomplished using an enzyme immunoassay to measure fecal concentrations of estradiol (E2) and progesterone. Fecal samples were collected from female FMD (aged 3-4 years) for one year, including during breeding and non-breeding seasons. Non-pregnant estrous cycles were recorded in females, based on fecal progesterone concentrations, their overall estrous cycle length was (mean±SEM) 24.3±0.5 days, with 21.6±0.5 days in the luteal phase and 2.7±0.3 days in the inter-luteal phase. Fecal progesterone and E2 concentrations were also measured in females that became pregnant and gave birth after gestating approximately 6 months. Two weeks after becoming pregnant, the average fecal progesterone concentration was significantly greater than that during non-pregnancy. The average fecal progesterone concentrations during pregnancy increased 3.2-fold above non-pregnant concentrations, decreasing to non-pregnant concentrations only after parturition. By contrast, average fecal E2 concentrations during gestation and after parturition were not different from average non-pregnant concentration. In addition, no difference was observed between progesterone concentration in the first month after pregnancy and the value during the luteal phase. However, progesterone concentration during the second month of pregnancy was significantly higher than the value during the luteal phase. In conclusion, monitoring fecal progesterone is an effective method for assessing ovarian function in FMD and will be a useful tool for breeding management and development of assisted

  5. Progesterone inhibits behavioral responses and estrogen increases corticosterone levels after acute cocaine administration.

    PubMed

    Niyomchai, Tipyamol; Russo, Scott J; Festa, Eugene D; Akhavan, Alaleh; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2005-04-01

    Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.

  6. Rational design of orally-active, pyrrolidine-based progesterone receptor partial agonists

    SciTech Connect

    Thompson, Scott K.; Washburn, David G.; Frazee, James S.; Madauss, Kevin P.; Hoang, Tram H.; Lapinski, Leahann; Grygielko, Eugene T.; Glace, Lindsay E.; Trizna, Walter; Williams, Shawn P.; Duraiswami, Chaya; Bray, Jeffrey D.; Laping, Nicholas J.

    2010-09-03

    Using the X-ray crystal structure of an amide-based progesterone receptor (PR) partial agonist bound to the PR ligand binding domain, a novel PR partial agonist class containing a pyrrolidine ring was designed. Members of this class of N-alkylpyrrolidines demonstrate potent and highly selective partial agonism of the progesterone receptor, and one of these analogs was shown to be efficacious upon oral dosing in the OVX rat model of estrogen opposition.

  7. Progesterone improves the number and quality of hormone induced Fowler toad (Bufo fowleri) oocytes

    PubMed Central

    Browne, Robert K; Li, Hong; Seratt, Jessica; Kouba, Andrew

    2006-01-01

    Combinations of progesterone, lutenizing hormone releasing hormone analogue (LHRHa), human chorionic gonadotrophin (hCG), and the dopamine-2 (DA2) receptor antagonist 1-[1-[4,4-bis(4-Fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one (Pimozide; Orap) were tested for improvement of spawning rates, oocyte numbers, fertilization and neurulation rates of the Fowler toad (Bufo fowleri). Only treatments combined with progesterone produced large numbers of oocytes. The best treatment on oocyte numbers, neurulation rates, and the number of neurulas was with 5 mg progesterone, 20 mic.g LHRHa, and 0.25 mg Pimozide. Progesterone (5 mg) with 60 mic.g LHRHa gave high spawning rates, oocyte numbers, and fertilization rates but neurulation rates were low. Progesterone alone in high repeated doses did not result in ovulation. High doses of LHRHa (60 mic.g) with hCG, progesterone, and Pimozide gave the greatest number of toads spawning, however, they resulted in low oocyte numbers, fertilization and neurulation rates. A low dose of LHRHa (4 mic.g) with hCG, or hCG alone as a second administration, and progesterone with Pimozide produced few good quality oocytes. Toads were given normal ovulatory doses of hormones 24 or 48 hrs after their initial dose, but these resulted in low oocyte numbers followed by poor fertilization. Overall, these results suggest that progesterone with a dose between 20 mic.g and 60 mic.g of LHRHa may be optimal for the induction of ovulation in these toads. Moreover, Pimozide can supplement low doses of LHRHa but not replace it. PMID:16451718

  8. New Aspects of Progesterone Interactions with the Actin Cytoskeleton and Neurosteroidogenesis in the Cerebellum and the Neuronal Growth Cone

    PubMed Central

    Wessel, Lisa; Olbrich, Laura; Brand-Saberi, Beate

    2014-01-01

    The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are able to synthesize progesterone de novo from cholesterol. Progesterone is described to have neuroprotective, neuroreparative, anti-degenerative, and anti-apoptotic effects in the CNS and the PNS. Thus, the first clinical studies promise new therapeutic options using progesterone in the treatment of patients with traumatic brain injury. Additionally, experimental data from different animal models suggest further positive effects of progesterone on neurological diseases such as cerebral ischemia, peripheral nerve injury and amyothropic lateral sclerosis. In regard to this future clinical use of progesterone, we discuss in this review the underlying physiological principles of progesterone effects in neuronal tissues. Mechanisms leading to morphological reorganizations of neurons in the CNS and PNS affected by progesterone are addressed, with special focus on the actin cytoskeleton. Furthermore, new aspects of a progesterone-dependent regulation of neurosteroidogenesis mediated by the recently described progesterone binding protein PGRMC1 in the nervous system are discussed. PMID:25141866

  9. Non-genomic immunosuppressive actions of progesterone inhibits PHA-induced alkalinization and activation in T cells.

    PubMed

    Chien, Eileen Jea; Chang, Ching-Pang; Lee, Wen-Feng; Su, Tsung-Hsien; Wu, Chia-Hsun

    2006-09-01

    Progesterone is an endogenous immunomodulator, and can suppress T-cell activation during pregnancy. When analyzed under a genome time scale, the classic steroid receptor pathway does not have any effect on ion fluxes. Therefore, the aim of this study was to investigate whether the non-genomic effects on ion fluxes by progesterone could immunosuppress phytohemagglutinin (PHA)-induced human peripheral T-cell activation. The new findings indicated that, first, only progesterone stimulated both [Ca2+]i elevation and pHi decrease; in contrast, estradiol or testosterone stimulated [Ca2+]i elevation and hydrocortisone or dexamethasone stimulated pHi decrease. Secondly, the [Ca2+]i increase by progesterone was dependent on Ca2+ influx, and the acidification was blocked by Na+/H+ exchange (NHE) inhibitor, 3-methylsulphonyl-4-piperidinobenzoyl, guanidine hydrochloride (HOE-694) but not by 5-(N,N-dimethyl)-amiloride (DMA). Thirdly, progesterone blocked phorbol 12-myristate 13-acetate (PMA) or PHA-induced alkalinization, but PHA did not prevent progesterone-induced acidification. Fourthly, progesterone did not induce T-cell proliferation; however, co-stimulation progesterone with PHA was able to suppress PHA-induced IL-2 or IL-4 secretion and proliferation. When progesterone was applied 72 h after PHA stimulation, progesterone could suppress PHA-induced T-cell proliferation. Finally, immobilization of progesterone by conjugation to a large carrier molecule (BSA) also stimulated a rapid [Ca2+]i elevation, pHi decrease, and suppressed PHA-induced proliferation. These results suggested that the non-genomic effects of progesterone, especially acidification, are exerted via plasma membrane sites and suppress the genomic responses to PHA. Progesterone might act directly through membrane specific nonclassical steroid receptors to cause immunomodulation and suppression of T-cell activation during pregnancy.

  10. Inhibitory Effect of Progesterone on Cervical Tissue Formation in a Three-Dimensional Culture System with Human Cervical Fibroblasts1

    PubMed Central

    House, Michael; Tadesse-Telila, Serkalem; Norwitz, Errol R.; Socrate, Simona; Kaplan, David L.

    2013-01-01

    ABSTRACT Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of the cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) cultures. For 2D culture, cells were seeded in 6-well plates and cultured with media supplemented with estradiol (10−8 M), progesterone (10−7 or 10−6 M), and vehicle. For 3D culture, the cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot analysis. In both 2D and 3D cultures, decreased collagen synthesis was seen with increased progesterone concentration. Three-dimensional cultures could be maintained significantly longer than 2D cultures, and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, the 3D scaffolds were cultured with estradiol (10−8 M) and five conditions: vehicle; 10−9, 10−8, or 10−7 M progesterone; or 10−7 M progesterone plus 10−6 M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix. PMID:24285720

  11. Plasma progesterone and blood metabolite profiles in post-partum small east African zebu cows.

    PubMed

    Tegegne, A; Entwistle, K W; Mukasa-Mugerwa, E

    1993-05-01

    Plasma progesterone profiles were used to monitor post-partum reproductive activity in 12 Small East African zebu (Bos indicus) cows allocated to either supplementary or no supplementary feeding (control) with continuous or restricted (twice daily) suckling regimes. Intact bulls were used for breeding. Blood samples were collected 3 times a week for 33 weeks to determine plasma progesterone levels. Weekly blood samples were also used to determine blood metabolite concentrations. Plasma progesterone levels remained below 1 ng/ml in all cows until week 12 post-partum. Only 5 cows showed ovarian activity over the 33 week period. Cows that cycled expressed irregular and short-lived progesterone rises (> 1 ng/ml) lasting 8 to 12 days prior to establishment of normal patterns of progesterone secretion where progesterone levels ranged from 8 to 10 ng/ml in cows with normal cycles. Plasma total protein, albumin, globulin, blood urea nitrogen and glucose levels varied over time without consistent trends, and were not influenced by either supplementary feeding of suckling regimes, nor differed between cyclic and acyclic cows. It was concluded that extended post-partum anoestrus, conception failure and early embryonic mortality were responsible for lowered reproductive efficiency in zebu cows. Blood metabolite concentrations were not good indicators of nutritional status and were not related to post-partum ovarian activity. PMID:8236477

  12. Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide

    SciTech Connect

    Chandrasekhar, Y.; Armstrong, D.T. )

    1991-07-01

    The authors have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with (3H)-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing (3H)-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen-induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus.

  13. Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

    PubMed Central

    Larsen, Bryan; Hwang, Joseph

    2011-01-01

    The uterine cervix plays a vital role in maintaining pregnancy and an equally important role in allowing parturition to occur. Progesterone, either endogenously produced or supplied exogenously, supports the function of the cervix in sustaining intrauterine pregnancy, and the withdrawal of progesterone, either through natural processes or pharmacologic intervention, leads to delivery which underscores the importance of the progesterone's biological activities manifest in normal gestation and pregnancy that ends prematurely. Research crossing many scientific disciplines has demonstrated that progesterone is a pleotropic compound that affects the cervix through cytoplasmic and membrane receptors with profound effects on cellular and molecular functions that influence inflammatory cascades and extracellular matrix, both of which have consequences for parturition. Beyond the local cell and molecular biology of progesterone, it has systemic effects of relevance to pregnancy as well. This paper examines the biology of the cervix from its gross to cellular structure and biological activities of its cell and molecular processes that may be affected by progesterone. The implications of these processes for preterm birth are explored, and direction of current research is in relation to translational medicine implications for diagnostic, prognostic, and therapeutic approaches to threatened preterm birth. PMID:22114461

  14. The influence of some sample handling factors on progesterone and testosterone analysis in goats.

    PubMed

    Fahmi, H A; Williamson, N B; Tibary, A; Hegstad, R L

    1985-08-01

    This study validated the use of commercially available radioimmunoassay kits for measuring the circulating progesterone and testosterone levels of goats. Progesterone and testosterone levels were then assayed in plasma which was collected from 23 does and 8 bucks. Collections from each animal were divided into three sodium fluoride-potassium oxalate (F/OX), one heparin, and one EDTA tubes and also into a tube without anticoagulant. Plasma from an F/OX tube was separated immediately from the blood cells by centrifugation. Serum or plasma was also separated after storage for 24 hours with F/OX, heparin or EDTA anticoagulant at 22 degrees C or with F/OX at 5 degrees C. A significant decline in assayable progesterone occurred in samples stored at 22 degrees C with each anticoagulant used and in the serum sample. Samples stored at 5 degrees C for 24 hours with F/OX anticoagulant contained concentrations of progesterone which did not differ significantly from those in samples where plasma was removed immediately. Assayable testosterone did not change with the anticoagulant used or vary with the storage temperature when F/OX tubes were stored at 5 degrees C and 22 degrees C for 24 hours. Results indicate that sample storage does influence levels of measured progesterone but not testosterone in goats. Progesterone assay is best done on plasma which is immediately separated from blood cells or on samples which are stored at 5 degrees C. PMID:16726076

  15. Estrogen receptor and progesterone receptor genes are expressed differentially in mouse embryos during preimplantation development.

    PubMed Central

    Hou, Q; Gorski, J

    1993-01-01

    Estrogen and progesterone play an important role in the development and implantation of preimplantation embryos. However, it is controversial whether these hormones act directly on the embryos. The effects of these hormones depend on the existence of their specific receptors. To determine whether estrogen receptor (ER) and progesterone receptor genes are expressed in mouse preimplantation embryos, we examined RNA from embryos at different stages of preimplantation development by reverse transcription-polymerase chain reaction techniques. ER mRNA was found in oocytes and fertilized eggs. The message level began to decline at the two-cell stage and reached its lowest level at the five- to eight-cell stage. ER mRNA was not detectable at the morula stage but reappeared at the blastocyst stage. Progesterone receptor mRNA was not detectable until the blastocyst stage. The embryonic expression of ER and progesterone receptor genes in the blastocyst suggests a possible functional requirement for ER and progesterone receptor at this stage of development. These results provide a basis for determining the direct role of estrogen and progesterone in preimplantation embryos. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8415723

  16. Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

    PubMed

    Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

    2015-06-01

    There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures.

  17. Progesterone improves cognitive performance and attenuates smoking urges in abstinent smokers

    PubMed Central

    Sofuoglu, Mehmet; Mouratidis, Maria; Mooney, Marc

    2010-01-01

    Summary Background Progesterone, a steroid hormone, has been implicated in many CNS functions including reward, cognition, and neuroprotection. The goal of this study was to examine the dose-dependent effects of progesterone on cognitive performance, smoking urges, and smoking behavior in smokers. Methods Thirty female and thirty-four male smokers participated in a double-blind, placebo-controlled study. Female smokers were in the early follicular phase of their menstrual cycle during study participation. Smokers were randomly assigned to either 200 or 400 mg/day of progesterone or placebo, given in two separate doses, during clinic visit. The first 3 days of the treatment period, smokers abstained from smoking, which was verified with breath CO levels. Smokers attended an experimental session on day 4 where the number of cigarettes smoked were recorded starting two hours after the medication treatment. Results Progesterone treatment, 200 mg/day, significantly improved cognitive performance in the Stroop and the Digit Symbol Substitution Test. Progesterone at 400 mg/day was associated with reduced urges for smoking but did not change ad lib smoking behavior. Conclusions These findings suggest a potential therapeutic value of progesterone for smoking cessation. PMID:20675057

  18. Progesterone reduces sympathetic tone without changing blood pressure or fluid balance in men.

    PubMed

    Tollan, A; Oian, P; Kjeldsen, S E; Eide, I; Maltau, J M

    1993-01-01

    There is scant information on the effects of progesterone on circulation. Changes in catecholamine levels, blood pressure and transcapillary fluid balance were measured in 12 men before and during administration of natural progesterone (Utrogestan). Before administration, systolic blood pressure was significantly correlated with venous adrenaline (r = 0.67, p = 0.01). There was a significant decrease (p = 0.004) in venous noradrenaline during progesterone administration, and systolic blood pressure was significantly correlated with the arteriovenous difference for noradrenaline (r = 0.66, p = 0.02). Serum progesterone, which attained levels similar to those found in women during the luteal phase, did not significantly alter blood pressure, body weight or intra- to extravascular fluid shift. It is concluded that progesterone may have a direct action by increasing the uptake of noradrenaline from the synaptic cleft or by decreasing the nerve firing rate. Interestingly, the pretreatment finding of a significant correlation between blood pressure and adrenaline was less evident during progesterone administration.

  19. Factors affecting the success of resynchronization protocols with or without progesterone supplementation in dairy cows

    PubMed Central

    Forro, Annette; Beindorff, Nicola; Sharifi, Ahmad Reza; Brozos, Christos; Bollwein, Heinrich

    2015-01-01

    The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR. PMID:25293490

  20. Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury

    PubMed Central

    Geddes, Rastafa I.; Peterson, Bethany L.; Stein, Donald G.; Sayeed, Iqbal

    2016-01-01

    Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone’s effects in the same model of brain injury but with pre-pubescent females. Methods Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1–7, and underwent behavioral testing from PID 9–27. Brains were evaluated for lesion size at PID 28. Results Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Conclusion Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI. PMID:26799561

  1. Disappearance and unexpected reappearance of progesterone in the circulation of the monkey: novel hormone kinetics.

    PubMed Central

    Kowalski, W B; Chatterton, R T; Kazer, R R; Severini, T A

    1996-01-01

    1. Intravenous injection of [3H]progesterone in non-pregnant monkeys resulted in total disappearance of the labelled hormone from the circulation within 3 h. However, 0.5-1.75 h after disappearance the hormone reappeared, reaching 20% (median, 5%) of the initial maximal concentration. 2. Reappearance of labelled hormone was accompanied by similar fluctuations in the levels of labelled metabolites, [3H]20 alpha-dihydroprogesterone and [3H]17 alpha-hydroxyprogesterone, which reached 61% (median, 14%) and 120% (median, 13%), respectively, of the initial maximal concentrations. 3. Chromatography was used to separate labelled progesterone and its metabolites. Efficiency of the procedure was determined separately in each sample and for each steroid. All data were corrected for percentage recovery. 4. Analytical equations were devised, based on the theory of compartmental systems with continuously distributed time lags, to describe the unexpected kinetics of progesterone levels. The coefficients of determination ranged from 86 to 99% (median, 96%) which indicates that the equations enabled reliable prediction of hormone levels in blood within the time range studied. 5. The unexpected reappearance of labelled progesterone cannot be explained by hormone secretion but only by a delayed release from tissue stores, since progesterone does not undergo enterohepatic recirculation. Thus, a previously undescribed mechanism affecting circulating progesterone levels, and perhaps those of other hormones, exists. PMID:8799907

  2. Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin(R) (progesterone) vaginal insert.

    PubMed

    Check, Jerome H

    2009-08-01

    Supplementation of progesterone in the luteal phase and continuance of progesterone therapy during the first trimester has been found in several studies to have benefits in promoting fertility, preventing miscarriages and even preventing pre-term labor. Though it can be administered orally, intramuscularly or even sublingually, a very effective route with fewer side effects can be achieved by an intravaginal route. The first vaginal preparations were not made commercially but were compounded by pharmacies. This had the disadvantage of lack of control by the Food and Drug Administration (FDA) ensuring efficacy of the preparations. Furthermore there was a lack of precise dosing leading to batch to batch variation. The first commercially approved vaginal progesterone preparation in the United States was a vaginal gel which has proven very effective. The main side effect was accumulation of a buildup of the vaginal gel sometimes leading to irritation. Natural micronized progesterone for vaginal administration with the brand name of Utrogestan A((R)) had been approved even before the gel in certain European countries. Endometrin((R)) vaginal tablets are the newest natural progesterone approved by the FDA. Comparisons to the vaginal gel and to intramuscular progesterone have shown similar efficacy especially in studies following controlled ovarian hyperstimulation and oocyte egg retrieval and embryo transfer. Larger studies are needed to compare side effects. PMID:19753133

  3. Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride.

    PubMed

    Wiebe, John P; Rivas, Martin A; Mercogliano, Maria F; Elizalde, Patricia V; Schillaci, Roxana

    2015-05-01

    Progesterone has long been linked to breast cancer but its actual role as a cancer promoter has remained in dispute. Previous in vitro studies have shown that progesterone is converted to 5α-dihydroprogesterone (5αP) in breast tissue and human breast cell lines by the action of 5α-reductase, and that 5αP acts as a cancer-promoter hormone. Also studies with human breast cell lines in which the conversion of progesterone to 5αP is blocked by a 5α-reductase inhibitor, have shown that the in vitro stimulation in cell proliferation with progesterone treatments are not due to progesterone itself but to the metabolite 5αP. No similar in vivo study has been previously reported. The objective of the current studies was to determine in an in vivo mouse model if the presumptive progesterone-induced mammary tumorigenesis is due to the progesterone metabolite, 5αP. BALB/c mice were challenged with C4HD murine mammary cells, which have been shown to form tumors when treated with progesterone or the progestin, medroxyprogesterone acetate. Cells and mice were treated with various doses and combinations of progesterone, 5αP and/or the 5α-reductase inhibitor, finasteride, and the effects on cell proliferation and induction and growth of tumors were monitored. Hormone levels in serum and tumors were measured by specific RIA and ELISA tests. Proliferation of C4HD cells and induction and growth of tumors was stimulated by treatment with either progesterone or 5αP. The progesterone-induced stimulation was blocked by finasteride and reinstated by concomitant treatment with 5αP. The 5αP-induced tumors expressed high levels of ER, PR and ErbB-2. Hormone measurements showed significantly higher levels of 5αP in serum from mice with tumors than from mice without tumors, regardless of treatments, and 5αP levels were significantly higher (about 4-fold) in tumors than in respective sera, while progesterone levels did not differ between the compartments. The results indicate that

  4. Compound I is the reactive intermediate in the first monooxygenation step during conversion of cholesterol to pregnenolone by cytochrome P450scc (CYP11A1): EPR / ENDOR/cryoreduction-annealing studies

    PubMed Central

    Davydov, Roman; Gilep, Andrey A.; Strushkevich, Natallia V.; Usanov, Sergey A.; Hoffman, Brian M.

    2012-01-01

    Cytochrome P450scc (CYP11A1) catalyzes conversion of cholesterol (CH) to pregnenolone, the precursor to all steroid hormones. This process proceeds via three sequential monooxygenation reactions: two stereospecific hydroxylations with formation first of 22R-hydroxycholesterol (22-HC) and then 20α,22R-dihydroxycholesterol (20,22-DHC), followed by the C20-C22 bond cleavage. Herein we have employed EPR and ENDOR spectroscopy to characterize the intermediates in the first hydroxylation step by 77K radiolytic one-electron cryoreduction and subsequent annealing of the ternary oxy cytochrome P450scc-cholesterol complex. This approach is fully validated by the demonstration that the cryoreduced ternary complex of oxy-P450scc-CH is catalytically competent and hydroxylates cholesterol to form 22R-HC with no detectable formation of 20-HC, just as occurs under physiological conditions. Cryoreduction of the ternary complex trapped at 77K produces predominantly the hydroperoxy-ferriheme P450scc intermediate, along with a minor fraction of peroxo-ferriheme intermediate that converts into a new hydroperoxo-ferriheme species at 145K. This behavior reveals that the distal pocket of the parent oxy-P450scc-cholesterol complex exhibits an efficient proton delivery network, with an ordered water molecule H-bonded to the distal oxygen of the dioxygen ligand. During annealing of the hydroperoxy-ferric P450scc intermediates at 185K they convert to the primary product complex in which CH has been converted to 22-HC. In this process, the hydroperoxy-ferric intermediate decays with a large sKIE, as expected when proton delivery to the terminal O leads to formation of Compound I (Cpd I). 1H ENDOR measurements of the primary product formed in deuterated solvent show that the heme Fe(III) is coordinated to the 22R-O1H of 22-HC, where the 1H is derived from substrate and exchanges to D after annealing at higher temperatures. These observations establish that Cpd I is agent that hydroxylates CH

  5. Vaginal ring delivery of selective progesterone receptor modulators for contraception

    PubMed Central

    Jensen, Jeffrey T.

    2013-01-01

    Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) are under development to address limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing, and therefore might improve the effectiveness of contraception. The principle contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1–2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL. PMID:23040126

  6. Vaginal ring delivery of selective progesterone receptor modulators for contraception.

    PubMed

    Jensen, Jeffrey T

    2013-03-01

    Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) is under development to address the limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing and therefore might improve the effectiveness of contraception. The principal contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate (UPA) is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1 and 2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6-7 ng/mL.

  7. Bone Growth and Turnover in Progesterone Receptor Knockout Mice

    PubMed Central

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jamie C.; Waters, Katrina M.; Lydon, John P.; O’Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-01-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and microcomputed tomography analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 wk of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain, and tibia longitudinal bone growth were normal in PRKO mice. In contrast, total, cancellous, and cortical bone mass were increased in the humerus of 12-wk-old PRKO mice, whereas cortical and cancellous bone mass in the tibia was normal. At 26 wk of age, cancellous bone area in the proximal tibia metaphysis of PRKO mice was 153% greater than age matched wild-type mice. The improved cancellous bone balance in 6-month-old PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice is not essential for bone growth and turnover. However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence. PMID:18276762

  8. Bone growth and turnover in progesterone receptor knockout mice.

    SciTech Connect

    Rickard, David J.; Iwaniec, Urszula T.; Evans, Glenda; Hefferan, Theresa E.; Hunter, Jaime C.; Waters, Katrina M.; Lydon, John P.; O'Malley, Bert W.; Khosla, Sundeep; Spelsberg, Thomas C.; Turner, Russell T.

    2008-05-01

    The role of progesterone receptor (PR) signaling in skeletal metabolism is controversial. To address whether signaling through the PR is necessary for normal bone growth and turnover, we performed histomorphometric and mCT analyses of bone from homozygous female PR knockout (PRKO) mice at 6, 12, and 26 weeks of age. These mice possess a null mutation of the PR locus, which blocks the gene expression of A and B isoforms of PR. Body weight gain, uterine weight gain and tibia longitudinal bone growth was normal in PRKO mice. In contrast, total and cortical bone mass were increased in long bones of post-pubertal (12 and 26-week-old) PRKO mice, whereas cancellous bone mass was normal in the tibia but increased in the humerus. The striking 57% decrease in cancellous bone from the proximal tibia metaphysis which occurred between 6 and 26 weeks in WT mice was abolished in PRKO mice. The improved bone balance in aging PRKO mice was associated with elevated bone formation and a tendency toward reduced osteoclast perimeter. Taken together, these findings suggest that PR signaling in mice attenuates the accumulation of cortical bone mass during adolescence and is required for early age-related loss of cancellous bone.

  9. The role of progesterone in oocyte acquisition of developmental competence.

    PubMed

    Fair, T; Lonergan, P

    2012-08-01

    It is generally accepted that progesterone (P4) is a key regulator of reproductive function in mammals. In cattle, the primary focus of P4's actions has been uterine receptivity and maintenance of pregnancy. Studies in mammalian laboratory species and ovarian derived cell lines also highlight their role in ovarian function. Extensive research in non-mammalian species has elucidated a critical role for P4 and both its nuclear and membrane-bound receptors in oocyte maturation and ovulation. Until recently, such a role in mammalian oocytes has been disputed. However, as oestrous synchronization regimes are constantly tweaked and revised to maximize pregnancy rates to artificial insemination in cattle, the importance of P4 priming of the dominant ingfollicle is once again tak centre stage. Sequencing of the bovine genome and the development of multiple transcriptomic data mining tools have facilitated an explosion in global transcriptome profiling of immature and matured oocytes and their surrounding cumulus cells. Many of the differentially regulated genes and their associated preferentially populated pathways appear to be P4 regulated in other tissues. Therefore, attention is once again turning to a potential role for P4 in ovulatory follicle development and oocyte maturation in cattle. The current review summarizes the most recent findings in these areas. PMID:22827363

  10. Competitive immunoassay of progesterone by microchip electrophoresis with chemiluminescence detection.

    PubMed

    Ye, Fanggui; Liu, Jinwen; Huang, Yong; Li, Shutin; Zhao, Shulin

    2013-10-01

    A sensitive and rapid homogeneous immunoassay method based on microchip electrophoresis-chemiluminescence detection (MCE-CL) using luminol-hydrogen peroxide as chemiluminescence system catalyzed by horseradish peroxidase (HRP) was developed for the determination of progesterone (P). The assay was based on the competitive immunoreactions between HRP-labeled P antigen (HRP-P) and P with a limited amount of anti-P mouse monoclonal antibody (Ab), and MCE separation of free HRP-P and HRP-P-Ab immunocomplex followed by CL detection. The effect of various factors such as conditions for the CL reaction, MCE and incubation time for the immunoreactions were examined and optimized. Under optimal assay conditions, the MCE separation was accomplished within 80s. The linear range of detection for P was 8-800nM with a detection limit of 3.8nM (signal/noise ratio=3). This present method has been applied to determine P in human serum samples from normal and pregnant women. The result indicates that the proposed MCE-CL based homogeneous immunoassay method can serve as an alternative tool for clinical assay of P.

  11. Mammary uptake and metabolism of progesterone in goats and its effect on milk progesterone concentrations during the oestrous cycle and early pregnancy.

    PubMed

    Holdsworth, R J; Heap, R B; Goode, J; Peaker, M; Walters, D E

    1983-08-01

    Following the observation that the concentration of progesterone in goats' milk differs appreciably according to the specificity of the antiserum used in a non-extraction (direct) radioimmunoassay, experiments were carried out to find an explanation for these results. Milk and plasma samples were collected during the oestrous cycle and during an equivalent period of pregnancy after a fertile mating. Samples were analyzed by a direct radioimmunoassay using two antisera, 18/3 which is highly specific for progesterone and 465/6 which is less specific, and by radioimmunoassay of fractions isolated by thin-layer chromatography (TLC). Values obtained for milk and plasma samples collected during the oestrous cycle and early pregnancy were similar, except that values for milk samples measured with antiserum 465/6 were higher in pregnancy compared to those obtained during the oestrous cycle. Values obtained for milk and plasma with antiserum 465/6 were significantly higher than those obtained with 18/3 (P less than 0.001). After TLC this difference was found to be due principally to the presence of compound(s) with chromatographic properties identical to 5-pregnanedione(s). A comparison of the concentration measured in arterial and mammary venous plasma and in milk showed that about 25% of progesterone (5.7 nmol/min) was extracted by the mammary gland, and that substantial amounts of immunoreactive metabolites of progesterone are secreted into milk with only small quantities being transferred into mammary vein plasma. PMID:6875433

  12. Progesterone attenuates astro- and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury.

    PubMed

    Labombarda, Florencia; González, Susana; Lima, Analia; Roig, Paulina; Guennoun, Rachida; Schumacher, Michael; De Nicola, Alejandro F

    2011-09-01

    Reactive gliosis, demyelination and proliferation of NG2+ oligodendrocyte precursor cells (OPC) are common responses to spinal cord injury (SCI). We previously reported that short-term progesterone treatment stimulates OPC proliferation whereas chronic treatment enhances OPC differentiation after SCI. Presently, we further studied the proliferation/differentiation of glial cells involved in inflammation and remyelination in male rats with SCI subjected to acute (3 days) or chronic (21 days) progesterone administration. Rats received several pulses of bromodeoyuridine (BrdU) 48 and 72 h post-SCI, and sacrificed 3 or 21 days post-SCI. Double colocalization of BrdU and specific cell markers showed that 3 days of SCI induced a strong proliferation of S100β+ astrocytes, OX-42+ microglia/macrophages and NG2+ cells. At this stage, the intense GFAP+ astrogliosis was BrdU negative. Twenty one days of SCI enhanced maturation of S100β+ cells into GFAP+ astrocytes, but decreased the number of CC1+ oligodendrocytes. Progesterone treatment inhibited astrocyte and microglia /macrophage proliferation and activation in the 3-day SCI group, and inhibited activation in the 21-day SCI group. BrdU/NG2 double labeled cells were increased by progesterone at 3 days, indicating a proliferation stimulus, but decreased them at 21 days. However, progesterone-enhancement of CC1+/BrdU+ oligodendrocyte density, suggest differentiation of OPC into mature oligondendrocytes. We conclude that progesterone effects after SCI involves: a) inhibition of astrocyte proliferation and activation; b) anti-inflammatory effects by preventing microglial activation and proliferation, and c) early proliferation of NG2+ progenitors and late remyelination. Thus, progesterone behaves as a glioactive factor favoring remyelination and inhibiting reactive gliosis.

  13. Secretion of progesterone and 20 alpha-dihydroprogesterone during the estrous cycle in goats.

    PubMed

    Sawada, T; Hou, M; Tamada, H; Mori, J

    1994-12-01

    The secretion of progesterone and 20 alpha-dihydroprogesterone (20 alpha-DHP) during the estrous cycle and the effects of prostaglandin F2 alpha (PGF2 alpha) and 20 alpha-DHP on the secretion of these two steroids during the midluteal phase in goats were studied. The mean progesterone concentration in the peripheral plasma was extremely low (< 0.01 ng/mL) on the day of estrus. The concentration increased to a maximum (7.80 ng/mL) on about day 10 after estrus, and decreased rapidly during the last 3 days of the cycle. The plasma concentration of 20 alpha-DHP also was low (0.86 ng/mL) on the day of estrus, but increased gradually after estrus and decreased gradually in the last 5 days of the cycle (to 3.22 ng/mL). The ratio of progesterone to 20 alpha-DHP was > 1 after day 2 of estrus, but decreased and fell to < 1 during the last 3 days of the cycle. An injection of 3 mg of PGF2 alpha decreased the secretion of progesterone within 30 min, but affected the secretion of 20 alpha-DHP little until 2 h. The ratio of progesterone to 20 alpha-DHP fell to < 1 after 24 h. Three of the five goats given such an injection came into estrus within 2 days, and the other two came into estrus within 3 days. An injection of 15 mg of 20 alpha-DHP did not affect progesterone secretion or the estrous cycle length. These results indicate that in the goat after estrus, there is much 20 alpha-DHP in the peripheral plasma. Progesterone may be catabolized to the biologically inactive steroid, 20 alpha-DHP, during luteolysis. PMID:7900164

  14. Influence of progesterone on serotonin metabolism: a possible causal factor for mood changes.

    PubMed

    Ladisich, W

    1977-01-01

    The influence of progesterone on gestagen upon stress reactions and the metabolism of the biogenic amines, noradrenaline (NA) and serotonin (5-HT), were evaluated. For the 1st experiments, the 54 subjects ranged in age from 18 to 30 years. Of these, 19 (35%) had reported premenstrual tension, depression, or somatic complaints. After a preliminary interview the Moss Menstrual Distress Questionnarie and the Eysenck Personality Inventory were completed. Each subject was subsequently seen at Day 8 before predicted menstruation and 1 day before menstruation. At each session, blood samples were taken for progesterone assay. The patients sat in a darkened room and were asked to memorize words heard from a tape recording while being given a mild electric shock. The morning after the session, subjects completed the Scale of Well-Being. Psychic difficulty shortly before menstruation was higher in 49 subjects; in 16.3% of these it was severe. Only 10.2% had a negative effect. There was a correlation between the different tests. Only in the medroxyprogesterone-treated group was there a significantly higher reaction to stress on Day 1 before menstruation than a week earlier. There were large individual variations. For studies of the effects of progesterone on NA metabolism, Sprague-Dawley rats which had been ovariectomized 3 weeks earlier, were given progesterone 20 mg/kg sc on 2 consecutive days. These animals were injected with tritiated NA intracisternally and underwent a stress procedure. 3 hours after the intracisternal injection, rats were killed and tritiated-NA and its metabolites estimated. Progesterone injections did not influence NA turnover or percentage distribution of tritiated-NA and its metabolites in unstressed rats but did increase 5-HT turnover. In stress-altered 5-HT metabolism an effect of progesterone was shown. Footshock also raised endogenous progesterone levels. PMID:561984

  15. Elevated progesterone during pseudopregnancy may prevent bone loss associated with low estrogen.

    PubMed

    Bowman, B M; Miller, S C

    1996-01-01

    There is increasing evidence for a role of endogenous progesterone in mineral and skeletal metabolism. The purpose of this study was to compare skeletal changes that occur during a condition of high endogenous progesterone but low estrogen (pseudopregnancy) with a condition of low endogenous progesterone and low estrogen (ovariectomy). Pseudopregnancy was selected over pregnancy to eliminate placental factors that may influence mineral metabolism. Rats were ovariectomized (OVX) or pseudopregnancy initiated, and bones were collected 13 days later. In some animals, blood was collected by indwelling catheters for determination of progesterone and estrogen levels. At mid-pseudopregnancy, there were substantial elevations in progesterone but estrogen was below the level of detection. Progesterone and estrogen were below the level of detection in the OVX rats. Longitudinal growth rates were increased compared with the normal cycling rats in both the pseudopregnant and OVX groups, indicative of decreased estrogen levels, but they were greatest in the OVX rats. Cancellous bone mass was maintained in the pseudopregnant rats compared with normal cycling rats but significantly reduced in the OVX animals. As expected, increased bone formation and turnover rates were observed in the OVX animals although some indices of bone formation were also increased in the pseudopregnant animals. Osteoclasts were significantly increased in the OVX but not the pseudopregnant animals compared with normal cycling rats. Increased periosteal bone formation indices are known to occur following OVX, but the greatest periosteal formation rates were observed in the pseudopregnant animals. While possible roles for some other endocrine agents cannot be excluded at this time, the data from the present study suggest that endogenous progesterone may have a role in the maintenance of bone mass perhaps by decreasing bone resorption while maintaining or increasing bone formation during physiological periods

  16. Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum

    PubMed Central

    Abu‐Hayyeh, Shadi; Ovadia, Caroline; Lieu, TinaMarie; Jensen, Dane D.; Chambers, Jenny; Dixon, Peter H.; Lövgren‐Sandblom, Anita; Bolier, Ruth; Tolenaars, Dagmar; Kremer, Andreas E.; Syngelaki, Argyro; Noori, Muna; Williams, David; Marin, Jose J.G.; Monte, Maria J.; Nicolaides, Kypros H.; Beuers, Ulrich; Oude‐Elferink, Ronald; Seed, Paul T.; Chappell, Lucy; Marschall, Hanns‐Ulrich; Bunnett, Nigel W.

    2015-01-01

    A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9‐15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first‐trimester samples all progesterone sulfates were significantly elevated in serum from low‐risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5‐dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high‐risk population. Delineation of a progesterone sulfate‐TGR5 pruritus axis identifies a therapeutic target for itch management in ICP. (Hepatology 2016;63:1287–1298) PMID:26426865

  17. Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns.

    PubMed

    Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

    2011-07-01

    Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.

  18. Secretion of progesterone during long and short days of the estrous cycle in goats that are continuous breeders.

    PubMed

    Sawada, T; Takahara, Y; Mori, J

    1995-03-01

    This study was conducted 1) to determine if the secretion of progesterone, as an index of ovarian activity, during the estrous cycle of nonseasonal Shiba goats is affected by seasonal changes, and 2) to learn if the pulsatile secretion of ovarian progesterone can be estimated from samples obtained by cannulation into the caudal vena cava via the femoral vein. Progesterone concentrations in jugular venous plasma during the estrous cycle in spring (May) were similar to those in autumn (November). Plasma progesterone concentrations in the jugular vein and caudal vena cava monitored for 10 h on Day 12 of the estrous cycle in spring were similar to those in autumn. The mean concentration (21.9 to 28.9 ng/ml) and the pulse frequency (6.2 to 7.4 pulses/10 h) of plasma progesterone in the caudal vena cava during both seasons were 3.1- to 4.7-fold and 1.7- to 2.4-fold those in the jugular vein, respectively. The degree of change in the peak magnitude and the base-line concentration of progesterone were higher in the caudal vena cava than in the jugular vein. These results indicate that progesterone secretion during the estrous cycle in nonseasonal goats is not affected by seasonal changes, and suggest that the pulsatile secretion of ovarian progesterone can be evaluated better from samples obtained from the caudal vena cava, near where progesterone is released, than from those obtained from the jugular vein. PMID:16727669

  19. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration

    PubMed Central

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  20. Progesterone Receptor Modulator for Emergency Contraception: A Randomized Controlled Trial

    PubMed Central

    Creinin, Mitchell D.; Schlaff, William; Archer, David F.; Wan, Livia; Frezieres, Ron; Thomas, Michael; Rosenberg, Michael; Higgins, James

    2010-01-01

    Objective Compare the efficacy and adverse effects of CDB-2914, a new progesterone receptor modulator, to levonorgestrel for emergency contraception. Methods We performed a randomized, double-blinded noninferiority trial, enrolling healthy women seeking emergency contraception within 72 hours of unprotected intercourse. Participants were randomly assigned to receive a single dose of 50 mg of CDB-2914, plus a placebo 12 hours later or two doses of 0.75 mg of levonorgestrel taken 12 hours apart. Follow-up was scheduled 5 to 7 days after the expected onset of the next menstrual period. Posttreatment pregnancy was established by a positive urine test at follow-up and confirmed by quantitative serum β-hCG. Daily diaries were used from the time of emergency contraception use until next menses to record adverse effects and sexual activity. Results Product efficacy was evaluable in 775 of CDB-2914 users and 774 of levonorgestrel users. Pregnancies occurred in 7 (0.9%, 95% confidence interval 0.2–1.6%) and 13 (1.7%, 95% confidence interval 0.8–2.6%) women, respectively. Based on the estimated cycle day of unprotected intercourse, 85% and 69% of anticipated pregnancies, respectively, were averted. Nausea was reported by a somewhat greater percentage of CDB-2914 than levonorgestrel users (29% compared with 24%, P=.03), but the distribution of other adverse effects was similar in both groups. Women in both groups experienced considerable variation in menstrual cycle length as compared with their reported individual normal cycle lengths. Conclusion CDB-2914 is at least as effective as levonorgestrel in preventing pregnancies after unprotected intercourse and has a similar side effect profile. PMID:17077229

  1. LC-MS/MS quantitation of plasma progesterone in cattle.

    PubMed

    Fernandes, R M T; Gomes, G C; Porcari, A M; Pimentel, J R V; Porciúncula, P M; Martins-Júnior, H A; Miguez, P H P; da Costa, J L; Amaral, P H; Perecin, F; Meurer, E C; Furtado, P V; Simas, R C; Eberlin, M N; Ferreira, C R; Madureira, E H

    2011-10-15

    Quantitation of progesterone (P(4)) in biological fluids is often performed by radioimmunoassay (RIA), whereas liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been used much less often. Due to its autoconfirmatory nature, LC-MS/MS greatly minimizes false positives and interference. Herein we report and compare with RIA an optimized LC-MS/MS method for rapid, efficient, and cost-effective quantitation of P(4) in plasma of cattle with no sample derivatization. The quantitation of plasma P(4) released from three nonbiodegradable, commercial, intravaginal P(4)-releasing devices (IPRD) over 192 h in six ovariectomized cows was compared in a pairwise study as a test case. Both techniques showed similar P(4) kinetics (P > 0.05) whereas results of P(4) quantitation by RIA were consistently higher compared with LC-MS/MS (P < 0.05) due to interference and matrix effects. The LC-MS/MS method was validated according to the recommended analytical standards and displayed P(4) limits of detection (LOD) and quantitation (LOQ) of 0.08 and a 0.25 ng/mL, respectively. The high selective LC-MS/MS method proposed herein for P(4) quantitation eliminates the risks associated with radioactive handling; it also requires no sample derivatization, which is a common requirement for LC-MS/MS quantitation of steroid hormones. Its application to multisteroid assays is also viable, and it is envisaged that it may provide a gold standard technique for hormone quantitation in animal reproductive science studies. PMID:21798587

  2. Progesterone and ovulation across stages of the transition to menopause

    PubMed Central

    O’Connor, Kathleen A.; Ferrell, Rebecca; Brindle, Eleanor; Trumble, Benjamin; Shofer, Jane; Holman, Darryl J.; Weinstein, Maxine

    2009-01-01

    Objective Detailed characterization of progesterone and ovulation across the menopausal transition provides insight into conception risk and mechanisms of reproductive aging. Design Participants (N=108, aged 25–58 years) collected daily urine specimens for six month intervals in each of five consecutive years. Specimens were assayed for pregnanediol-glucuronide (PDG), LH, FSH and estrone-glucuronide (E1G). Reproductive stage was determined using cycle length variance. A hierarchical algorithm was used to identify ovulation. Linear mixed-effects models estimated: 1) the frequency and day of ovulation by age and stage; 2) differences in FSH, LH, and E1G levels between ovulatory (O) and anovulatory (AO) cycles; and 3) total PDG levels and PDG levels in ovulatory cycles by age and stage. Results The probability of AO cycles increased across the perimenopause (p<.0001); reproductive stage was a stronger predictor than age of the probability of anovulation. Most cycles in late perimenopause were anovulatory (>60%), but one quarter of cycles longer than 60 days were ovulatory. Average day of ovulation was later in the late perimenopause (mean (SD) cycle day 27 (25)) compared to the premenopause. FSH and LH levels were higher, and E1G levels lower, in AO than O cycles (p<.0001 for each). Total PDG decreased in the late perimenopause, but 95th percentile PDG in ovulatory cycles declined steadily across the transition. Conclusions Exposure to the risk of conception in women experiencing cycles long enough to classify them as late perimenopausal is far from negligible. Reproductive stage is more informative than age about PDG levels and the likelihood of anovulation. PMID:19568209

  3. Respiratory effects of pregnancy and progesterone in Jersey cows.

    PubMed

    Keith, I M; Bisgard, G E; Manohar, M; Klein, J; Bullard, V A

    1982-12-01

    Unanesthetized Jersey cows were studied during both pregnant (5-9 months) nonlactating states, and nonpregnant lactating states; and also following treatment with progesterone (Pr). The pH, PCO2 and PO2 of aortic blood, VE and f were measured and the mixed expired gas was analyzed. The following significant changes from the nonpregnant state occurred during pregnancy: PaCO2 = -3.2 mm Hg, pHa = +0.02 unit, VT = -0.44 L, f = +7 breaths/min, and VE/VCO2 = +9.7. Concomitant with the respiratory studies, serum Pr levels were determined by radioimmunoassay (RIA) in 11 nonpregnant and 5 pregnant cows, and in 6 nonpregnant, lactating cows prior to and on days 3, 5 and 10 of treatment with Pr (500 mg, i.m., twice daily). Minute ventilation (VE, L X min-1 X kg-1, BTPS) was positively correlated (r = +0.59) and PaCO2 was negatively correlated (r = -0.64) with endogenous serum Pr levels of non-pregnant and pregnant cows. However, exogenous Pr did not significantly alter these parameters or pHa, despite mean serum levels nearly twice (23.6 +/- 10.2 ng/ml) those observed in pregnant cows (12.7 +/- 3.7 ng/ml). The increased ventilation during pregnancy in Jersey cows, shown in this study, does not appear to be related to Pr as exogenous Pr failed to induce hyperventilation. The correlation of increased ventilation with endogenous Pr levels therefore suggests that the mode of in vivo Pr release, or different compound, simultaneously released, could be the stimulus.

  4. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    SciTech Connect

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-11-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with (17 alpha-methyl-TH)promegestone ((TH)R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of (3H)R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of (TH)R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.

  5. Timing of follicular phase events and the postovulatory progesterone rise following synchronisation of oestrus in cows.

    PubMed

    Starbuck, G R; Gutierrez, C G; Peters, A R; Mann, G E

    2006-07-01

    In cows the timing of both ovulation and the subsequent postovulatory progesterone rise are critical to successful fertilisation and early embryo development. The aim of this study was to determine the degree of variability in the timing of ovulation relative to other follicular phase events and to determine how variations in the timing of follicular phase events contribute to the timing of the postovulatory progesterone rise. Plasma concentrations of progesterone, oestradiol and luteinising hormone (LH) and the timing of oestrus and ovulation were determined following induction of luteolysis were determined in 18 mature, non-lactating Holstein-Friesian cows. Four cows were excluded on the basis of abnormal reproductive function. In the remaining 14 cows oestrus occurred at 57.4+/-4.3h and the LH surge at 54.6+/-4.0h following luteolysis (progesterone <1ngmL(-1)) followed by a fall in circulating oestradiol concentration at 64.6+/-4.4h. Cows ovulated at 88.0+/-4.7h with the postovulatory progesterone rise (to >1ngmL(-1)) occurring 159+/-7.2h after luteolysis. There was considerable variation in the timing of ovulation following luteolysis (range 64-136h) onset of oestrus (range 24-40h) and onset of the LH surge (range 24-44h). Cows were then split on the basis of interval from progesterone fall to progesterone rise giving groups (n=7 per group) with intervals of 180.6+/-6.7 and 138.3+/-5.7h (P<0.001). Between groups, both the intervals from luteolysis to ovulation (98.3+/-6.9 vs 77.7+/-3.4h; P<0.05) and ovulation to progesterone rise (82.3+/-4.2 vs. 60.6+/-5.5h; P<0.01) were longer in late rise cows. There was no difference between groups in the interval from oestrus or LH surge to ovulation. In conclusion the results of this study further highlight the high variability that exists in the timing and interrelationships of follicular phase events in the modern dairy cow, reemphasising the challenges that exist in optimising mating strategies. However, the data do

  6. Regulation of hepatic progesterone and estrogen receptors in the female turtle, Chrysemys picta: relationship to vitellogenesis.

    PubMed

    Custodia-Lora, Noemí; Novillo, Apolonia; Callard, Ian P

    2004-04-01

    Previous studies using the fresh water turtle Chrysemys picta have demonstrated the differential expression of the two progesterone receptor isoforms (PRA and PRB) in the liver during the turtle seasonal cycle, correlating with ER mRNA levels and hepatic vitellogenesis. During the inter-vitellogenic periods the ratio of PRB:PRA favors PRA, suggesting that the PRB:PRA ratio may be important in the regulation of vitellogenesis. Based on these and other studies we hypothesize that progesterone may have differential effects on the estrogen (E)-induced vitellogenin response (inhibitory or stimulatory), depending on the PRB:PRA ratio. In this study, we determined the expression pattern and the hormonal regulation of progesterone receptor (PR) isoforms in the liver, during the estrogen-induced vitellogenin response in female C. picta. Northern blot analysis was used to evaluate the changes in vitellogenin mRNA, estrogen receptor (ER) mRNA, and PR mRNA expression; Western blot to determine changes in PR isoform expression and a homologous ELISA for measurement of plasma vitellogenin. The expression of PR isoforms in the liver of female turtles at the mRNA and protein levels was differentially regulated by estradiol and progesterone. Estradiol treatment enhanced the transcription of PR mRNA isoforms and possibly translation and/or increased stability of PRB protein in the female turtle liver. In contrast, this hormone decreased PRA protein levels. Progesterone alone down-regulated progesterone receptor isoform A (PRA) and progesterone receptor isoform B (PRB) proteins equally, but did not affect PR mRNA levels. Estradiol markedly increased hepatic ER mRNA, vtg mRNA, and vtg in plasma, but this effect was not impacted significantly by progesterone. The results presented here indicate that in female turtles hepatic PRB:PRA ratios are markedly changed by estradiol treatment due primarily to a decrease in PRA. The change in the PRB:PRA ratio after hormonal treatment confirms

  7. 2-Methoxyestradiol inhibits progesterone-dependent tissue factor expression and activity in breast cancer cells.

    PubMed

    Quezada, Marisol; Diaz, Jorge; Henriquez, Soledad; Bravo, Maria Loreto; Aranda, Evelyn; Oliva, Barbara; Villalon, Manuel; Kato, Sumie; Cuello, Mauricio A; Brosens, Jan J; Lange, Carol A; Owen, Gareth I

    2010-06-01

    2-Methoxyestradiol (2ME) is an endogenous metabolite of 17β-estradiol with antiangiogenic and antitumor properties, although its mechanisms of action remain unclear. Progestins in hormone replacement therapy increase the risk of breast cancer. Progesterone also enhances the procoagulant activity and invasive potential of progesterone receptor (PR)-positive breast cancer cell lines, an effect largely mediated by induction of tissue factor (TF), the cellular activator of the coagulation cascade. Here we show that 2ME abrogates the induction TF expression in progesterone-treated breast cancer cells via a mechanism that does not involve the estrogen receptor. Instead, we demonstrate that by selectively antagonizing ERK1/2 signaling in breast cancer cells, 2ME limits the transactivation potential of ligand-bound PR and inhibits the expression of endogenous progesterone targets, such as TF and signal transducer and activator of transcription 5. We further demonstrate that 2ME can alter the phosphorylation status of PR. Thus, 2ME prevents progesterone-dependent increase in breast cancer cell invasiveness and procoagulant activity by uncoupling PR from the ERK1/2 signal transduction pathway.

  8. Evidence for independent evolution of functional progesterone withdrawal in primates and guinea pigs

    PubMed Central

    Nnamani, Mauris C.; Plaza, Silvia; Romero, Roberto; Wagner, Günter P.

    2013-01-01

    Background and objectives: Cervix remodeling (CRM) is a critical process in preparation for parturition. Early cervix shortening is a powerful clinical predictor of preterm birth, and thus understanding how CRM is regulated is important for the prevention of prematurity. Humans and other primates differ from most other mammals by the maintenance of high levels of systemic progesterone concentrations. Humans have been hypothesized to perform functional progesterone withdrawal (FPW). Guinea pigs are similar to humans in maintaining high-progesterone concentrations through parturition, thus making them a prime model for studying CRM. Here, we analyze the phylogenetic history of FPW and document gene expression in the guinea pig uterine cervix. Methodology: Data on progesterone withdrawal were collected from the literature, and character evolution was analyzed. Uterine cervix samples were collected from non-pregnant, mid-pregnant and late pregnant guinea pigs. RNA was extracted and sequenced. Relative transcript levels were estimated and compared among sample groups. Results: The phylogenetic analysis shows that FPW evolved independently in primates and guinea pigs. The transcriptome data confirms that guinea pigs down-regulate progesterone receptor toward parturition, in contrast to humans. Some of the similarities between human and guinea pig are: down-regulation of estrogen receptor, up-regulation of VCAN and IGFBP4 as well as likely involvement of prostaglandins. Conclusions and implications: (i) FPW in guinea pigs evolved independently from that in primates. (ii) A small set of conserved gene regulatory changes has been detected. PMID:24481205

  9. A Progesterone-CXCR4 Axis Controls Mammary Progenitor Cell Fate in the Adult Gland

    PubMed Central

    Shiah, Yu-Jia; Tharmapalan, Pirashaanthy; Casey, Alison E.; Joshi, Purna A.; McKee, Trevor D.; Jackson, Hartland W.; Beristain, Alexander G.; Chan-Seng-Yue, Michelle A.; Bader, Gary D.; Lydon, John P.; Waterhouse, Paul D.; Boutros, Paul C.; Khokha, Rama

    2015-01-01

    Summary Progesterone drives mammary stem and progenitor cell dynamics through paracrine mechanisms that are currently not well understood. Here, we demonstrate that CXCR4, the receptor for stromal-derived factor 1 (SDF-1; CXC12), is a crucial instructor of hormone-induced mammary stem and progenitor cell function. Progesterone elicits specific changes in the transcriptome of basal and luminal mammary epithelial populations, where CXCL12 and CXCR4 represent a putative ligand-receptor pair. In situ, CXCL12 localizes to progesterone-receptor-positive luminal cells, whereas CXCR4 is induced in both basal and luminal compartments in a progesterone-dependent manner. Pharmacological inhibition of CXCR4 signaling abrogates progesterone-directed expansion of basal (CD24+CD49fhi) and luminal (CD24+CD49flo) subsets. This is accompanied by a marked reduction in CD49b+SCA-1− luminal progenitors, their functional capacity, and lobuloalveologenesis. These findings uncover CXCL12 and CXCR4 as novel paracrine effectors of hormone signaling in the adult mammary gland, and present a new avenue for potentially targeting progenitor cell growth and malignant transformation in breast cancer.

  10. Progesterone Treatment Shows Benefit in a Pediatric Model of Moderate to Severe Bilateral Brain Injury

    PubMed Central

    Geddes, Rastafa I.; Sribnick, Eric A.; Sayeed, Iqbal; Stein, Donald G.

    2014-01-01

    Purpose Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury. Methods Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1–7, subjected to behavioral testing from PID 9–27, and analyzed for lesion size at PID 28. Results The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats. Conclusion Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits. PMID:24489882

  11. Progesterone receptor subunits are high-affinity substrates for phosphorylation by epidermal growth factor receptor.

    PubMed Central

    Ghosh-Dastidar, P; Coty, W A; Griest, R E; Woo, D D; Fox, C F

    1984-01-01

    Purified preparations of epidermal growth factor (EGF) receptor were used to test hen oviduct progesterone receptor subunits as substrates for phosphorylation catalyzed by EGF receptor. Both the 80-kilodalton (kDa) (A) and the 105-kDa (B) progesterone receptor subunits were phosphorylated in a reaction that required EGF and EGF receptor. No phosphorylation of progesterone receptor subunits was observed in the absence of EGF receptor, even when Ca2+ was substituted for Mg2+ and Mn2+. Phospho amino acid analysis revealed phosphorylation at tyrosine residues, with no phosphorylation detectable at serine or threonine residues. Two-dimensional maps of phosphopeptides generated from phosphorylated 80- or 105-kDa subunits by tryptic digestion revealed similar patterns, with resolution of two major, several minor, and a number of very minor phosphopeptides. The Km of progesterone receptor for phosphorylation by EGF-activated EGF receptor was 100 nM and the Vmax was 2.5 nmol/min per mg of EGF receptor protein at 0 degrees C. The stoichiometry of phosphorylation/hormone binding for progesterone receptor subunits was 0.31 at ice-bath temperature and approximately 1.0 at 22 degrees C. Images PMID:6200881

  12. Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

    PubMed Central

    Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

    2015-01-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

  13. A Specific Transitory Increase in Intracellular Calcium Induced by Progesterone Promotes Acrosomal Exocytosis in Mouse Sperm.

    PubMed

    Romarowski, Ana; Sánchez-Cárdenas, Claudia; Ramírez-Gómez, Héctor V; Puga Molina, Lis del C; Treviño, Claudia L; Hernández-Cruz, Arturo; Darszon, Alberto; Buffone, Mariano G

    2016-03-01

    During capacitation, sperm acquire the ability to undergo the acrosome reaction (AR), an essential step in fertilization. Progesterone produced by cumulus cells has been associated with various physiological processes in sperm, including stimulation of AR. An increase in intracellular Ca(2+) ([Ca(2+)]i) is necessary for AR to occur. In this study, we investigated the spatiotemporal correlation between the changes in [Ca(2+)]i and AR in single mouse spermatozoa in response to progesterone. We found that progesterone stimulates an [Ca(2+)]i increase in five different patterns: gradual increase, oscillatory, late transitory, immediate transitory, and sustained. We also observed that the [Ca(2+)]i increase promoted by progesterone starts at either the flagellum or the head. We validated the use of FM4-64 as an indicator for the occurrence of the AR by simultaneously detecting its fluorescence increase and the loss of EGFP in transgenic EGFPAcr sperm. For the first time, we have simultaneously visualized the rise in [Ca(2+)]i and the process of exocytosis in response to progesterone and found that only a specific transitory increase in [Ca(2+)]i originating in the sperm head promotes the initiation of AR. PMID:26819478

  14. Nano-SPRi Aptasensor for the Detection of Progesterone in Buffer

    PubMed Central

    Zeidan, Effat; Shivaji, Renuka; Henrich, Vincent C.; Sandros, Marinella G.

    2016-01-01

    Progesterone is a steroid hormone that plays a central role in the female reproductive processes such as ovulation and pregnancy with possible effects on other organs as well. The measurement of progesterone levels in bodily fluids can assist in early pregnancy diagnosis and can provide insight for other reproductive functions. In this work, the detection of progesterone was examined by integrating novel aptamer development with a nanoEnhanced surface plasmon resonance imaging sensor. First, we developed X-aptamers and selected them for binding to progesterone. Then, we took advantage of the multi-array feature of SPRi to develop an optimized biosensor capable of simultaneously screening the 9 X-aptamers developed to determine the binding capabilities of each aptamer. The sensor surface design conditions were further optimized for the sandwich assay, which employed nanoEnhancers (NIR-streptavidin coated quantum dots) for ultrasensitive detection of progesterone molecules. The assay designed was examined over a concentration range of 1.575 ng/mL to 126 μg/mL resulting in a limit of detection (LOD) of 1.575 ng/mL (5 nM) in phosphate buffer. PMID:27216648

  15. Inhibition of human placental progesterone and estrogen synthesis in early human gestation by aminoglutethimide in vivo.

    PubMed

    Rabe, T; Mösch, R; Franke, C; Nobakht, N; Runnebaum, B

    1983-03-01

    The inhibitory effect of d,l-aminoglutethimide (AG) on the synthesis of progesterone and estradiol in early human pregnancy (8th-12th week of gestation) was investigated in volunteers; control group (n = 11), AG group [1000 mg AG orally at test begin (n = 6)]. Venous blood samples were taken at the beginning of the test and 0.5, 1, 2, 4, 8 and 24 h thereafter. In controls, no significant changes in serum progesterone and estradiol could be observed during 24 h. In the AG group, a decrease in progesterone and estradiol could be observed within 1 h after the test began; lowest serum steroid concentrations were reached after 4 h. Relative to the initial values taken as 100%, the greatest decrease in progesterone ranged between 37 and 83%, 62 +/- 15% (means +/- SD)(n = 6); the greatest decrease in estradiol ranged between 32 and 78%, 51 +/- 17% (means +/- SD)(n = 6). Twenty four hours after AG treatment, both steroids reached similar concentrations to those found at test begin. No clinical signs (e.g. uterine bleeding, contractions) for the abortifacient action of AG were observed. In conclusion, a single dose of AG (1000 mg given orally) cannot induce a therapeutic abortion in early pregnancy. In accordance with in vitro studies, the inhibitory effect of AG on placental progesterone formation is due to an inhibition of mitochondrial cholesterol side chain cleavage. The decrease in estradiol is thought to be related to an inhibition of placental aromatase.

  16. Plasma progesterone levels during pregnancy and pseudo-pregnancy in the hare (Lepus europaeus syriacus).

    PubMed

    Stavy, M; Terkel, J; Kohen, F

    1978-09-01

    A triphasic pattern of progesterone secretion was observed in female hares sampled throughout pregnancy and pseudopregnancy. After injection of hCG and artificial insemination (Day 1), progesterone values rose to a peak of 41.4 ng/ml about Day 14, remained at this level, then declined around Day 20 before increasing sharply to maximum levels of 67.7 ng/ml after midpregnancy (Day 28). Levels remained high for several days, then declined until Day 38, increased again until Day 41, before decreasing towards parturition. Progesterone levels were still high (37.5 ng/ml) 24h before parturition. The progesterone pattern during pseudopregnancy closely resembled that observed during the first half of pregnancy: levels rose from Day 2 to a peak at Days 11--18, then declined sharply to baseline levels around Day 22. It is suggested that the control of progesterone secretion might be transferred from the pituitary to the placenta at the beginning of the second half of pregnancy.

  17. Progesterone treatment for experimental stroke: an individual animal meta-analysis.

    PubMed

    Wong, Raymond; Renton, Cheryl; Gibson, Claire L; Murphy, Stephanie J; Kendall, David A; Bath, Philip M W

    2013-09-01

    Preclinical studies suggest progesterone is neuroprotective after cerebral ischemia. The gold standard for assessing intervention effects across studies within and between subgroups is to use meta-analysis based on individual animal data (IAD). Preclinical studies of progesterone in experimental stroke were identified from searches of electronic databases and reference lists. Corresponding authors of papers of interest were contacted to obtain IAD and, if unavailable, summary data were obtained from the publication. Data are given as standardized mean differences (SMDs, continuous data) or odds ratios (binary data), with 95% confidence intervals (95% CIs). In an unadjusted analysis of IAD and summary data, progesterone reduced standardized lesion volume (SMD -0.766, 95% CI -1.173 to -0.358, P<0.001). Publication bias was apparent on visual inspection of a Begg's funnel plot on lesion volume and statistically using Egger's test (P=0.001). Using individual animal data alone, progesterone was associated with an increase in death in adjusted analysis (odds ratio 2.64, 95% CI 1.17 to 5.97, P=0.020). Although progesterone significantly reduced lesion volume, it also appeared to increase the incidence of death after experimental stroke, particularly in young ovariectomized female animals. Experimental studies must report the effect of interactions on death and on modifiers, such as age and sex.

  18. Effect of progesterone treatment due to threatened abortion in early pregnancy for obstetric and perinatal outcomes.

    PubMed

    Duan, Lijun; Yan, Denglu; Zeng, Weiyue; Yang, Xiao; Wei, Qiang

    2010-01-01

    Progesterone supplementation has been used in a large number of women with threatened abortion for decades, despite various degrees of success, and contradictory and ever-changing views about its efficacy. The majority of previous literature has mainly focused on evaluation the effect of progesterone on pregnancy outcome of threatened abortion. No controlled epidemiological studies of obstetric and perinatal outcomes, including preterm birth, pregnancy complications and low birth weight newborns, in pregnant women with progesterone treatment have been published. The data of 523 pregnant women with progesterone treatment in the second and third months of pregnancy due to threatened abortion was compared with the data of other 21,054 pregnant women in the Department of Obstetrics, West China Second University Hospital for a period of 6years from January 2002 to October 2008. There was no difference in mean gestational age at delivery and birth weight, in addition the rate of preterm birth, pregnancy complications and low birth weight newborns. Intramuscular progesterone treatment due to threatened abortion during early pregnancy did not associate with a higher risk for pregnancy complications, preterm birth and low birth weight newborns. PMID:20079582

  19. Modeling of progesterone-induced intracellular calcium signaling in human spermatozoa.

    PubMed

    Li, Long-Fei; Xiang, Cheng; Zhu, Ya-Bing; Qin, Kai-Rong

    2014-06-21

    Calcium ion is a secondary messenger of mammalian spermatozoa. The dynamic change of its concentration plays a vital role in the process of sperm motility, capacitation, acrosome and fertilization. Progesterone released by the cumulus cells, as a potent stimulator of fertilization, can activate the calcium channels on the plasma membrane, which in turn triggers the dynamic change of intracellular calcium concentration. In this paper, a mathematical model of calcium dynamic response in mammalian spermatozoa induced by progesterone is proposed and numerical simulation of the dynamic model is conducted. The results show that the dynamic response of calcium concentration predicted by the model is in accordance with experimental evidence. The proposed dynamic model can be used to explain the phenomena observed in the experiments and predict new phenomena to be revealed by experimental investigations, which will provide the basis to quantitatively investigate the fluid mechanics and biochemistry for the sperm motility induced by progesterone.

  20. Placental production of progesterone in ovariectomized goats treated with a synthetic progestagen to maintain pregnancy.

    PubMed

    Sheldrick, E L; Ricketts, A P; Flint, A P

    1980-11-01

    Pregnant goats were ovariectomized or lutectomized and treated with medroxyprogesterone acetate. The circulating concentration of progesterone, which was reduced by 85% after ovariectomy or lutectomy, increased almost 3-fold between 120 and 140 days gestation, suggesting increased placental secretion. Measurement of veno-arterial differences across the uterus confirmed that an intrauterine organ was secreting progesterone at this time. Progesterone levels decreased (by 38%) in intact animals treated with medroxyprogesterone acetate alone. Concentrations of total unconjugated oestrogens were not altered by ovariectomy or lutectomy or by medroxyprogesterone acetate alone, but were related to the birth weight of the kids. Chronic treatment with medroxyprogesterone acetate reduced milk yield during lactation by up to 64%. PMID:7431343

  1. Dose of progesterone and allantoic fluid volume in conceptuses in ovariectomised goats.

    PubMed

    McGovern, P T

    1976-01-01

    The volume and composition of fetal fluids in conceptuses from untreated goats and from ovariectomised goats in which pregnancy was maintained with a high (0-76 mg per kg body weight) or low (0-35 mg per kg body weight) dose of progesterone, were determined. The mean allantoic fluid volume per conceptus was similar in the untreated goats (77-0+/-13-49 ml) and the ovariectomised goats which received the higher dose of progesterone (81-4+/-18-24 ml) but was significantly greater in the ovariectomised goats which received the lower dose of progesterone (251-5+/-66-49 ml). The increase in allantoic fluid was associated with a rise in K+ concentration. PMID:943819

  2. Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy.

    PubMed

    Vadivelu, Sudhakar; Sharer, Leroy; Schulder, Michael

    2010-05-01

    The authors present the case of a patient that demonstrates the long-standing use of megestrol acetate, a progesterone agonist, and its association with multiple intracranial meningioma presentation. Discontinuation of megestrol acetate led to shrinkage of multiple tumors and to the complete resolution of one tumor. Histological examination demonstrated that the largest tumor had high (by > 25% of tumor cell nuclei) progesterone-positive expression, including progesterone receptor (PR) isoform B, compared with low expression of PR isoform A; there was no evidence of estrogen receptor expression and only unaccentuated collagen expression. This is the first clinical report illustrating a causal relationship between exogenous hormones and modulation of meningioma biology in situ. PMID:19731987

  3. [Bovine milk progesterone concentration as a method of early diagnosis of pregnancy (author's transl)].

    PubMed

    Guissi, G; Laborde, N P; Rosner, J M

    1976-01-01

    With the purpose of obtaining an early indicator of pregnancy in bovines, excretion levels of milk progesterone were determined by a simple radioimmunological method. In the pregnant group, progesterone concentration was significantly (p less than 0,001) greater than in non-pregnant ones. In some cases (20-25%) there was no difference in values, resulting a method efficiency of 75-80%. Milk must be processed a few hours after collection since a decrease in progesterone values is observed within a few days. Easy obtention of this biological matherial, without special technical requirements as well as the simple dosification method make this test a practical index for establishing early diagnosis of pregnancy in bovines.

  4. Asperosaponin VI promotes progesterone receptor expression in decidual cells via the notch signaling pathway.

    PubMed

    Gao, Jie; Zhou, Chun; Li, Yadi; Gao, Feixia; Wu, Haiwang; Yang, Lilin; Qiu, Weiyu; Zhu, Lin; Du, Xin; Lin, Weixian; Huang, Dandan; Liu, Haibin; Liang, Chun; Luo, Songping

    2016-09-01

    Recurrent spontaneous abortion (RSA) is a common clinical condition, but its reasons remain unknown in 37-79% of the affected women. The steroid hormone progesterone (P4) is an integral mediator of early pregnancy events, exerting its effects via the progesterone receptor (PR). Dipsaci Radix (DR) has long been used for treating gynecological diseases in Chinese medicine, while its molecular mechanisms and active ingredients are still unclear. We report here the progesterone-like effects of the alcohol extraction and Asperosaponin VI from DR in primary decidual cells and HeLa cell line. We first determined the safe concentration of Asperosaponin VI in the cells with MTT assay and then found by using dual luciferase reporter and Western blotting that Asperosaponin VI significantly increased PR expression. Moreover, we explored the mechanisms of action of the DR extracts and Asperosaponin VI, and the results showed that they could activate Notch signaling, suggesting that they may function by promoting decidualization. PMID:27370099

  5. Biotransformation of Progesterone by Whole Cells of Filamentous Fungi Aspergillus brasiliensis

    PubMed Central

    Hosseinabadi, Tahereh; Vahidi, Hossein; Nickavar, Bahman; Kobarfard, Farzad

    2015-01-01

    Microbial steroid biotransformations have found a wide-reaching application for the production of more precious and functionalized compounds due to their high regio-and stereo selectivity. In this study, the possibility of using filamentous fungi Aspergillus brasiliensiscells in the biotransformation of progesterone, a C-21 steroid hormone was studied for the first time. The fungal strain was inoculated into the transformation medium supplemented with progesterone as a substrate. Biotransformation of this steroid for 7 days afforded 3 different hydroxylated metabolites: 11α-hydroxy progesterone; 14α-hydroxyprogesteroneand21-hydroxyprogesterone. The metabolites were separated by thin layer chromatography. Structure determinations of the metabolites were performed by comparing NMR, MS and IR spectra of the starting compound with those of metabolites. These results may be of industrial importance because the metabolites can be used as precursor of some steroid drugs. PMID:26330881

  6. Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives

    SciTech Connect

    Kloosterboer, H.J.; Vonk-Noordegraaf, C.A.; Turpijn, E.W.

    1988-09-01

    The relative binding affinities (RBAs) of four progestational compounds (norethisterone, levonorgestrel, 3-keto-desogestrel and gestodene) for the human progesterone and androgen receptors were measured in MCF-7 cytosol and intact MCF-7 cells. For the binding to the progesterone receptor, both Org 2058 and Org 3236 (or 3-keto-desogestrel) were used as labelled ligands. The following ranking (low to high) for the RBA of the nuclear (intact cells) progesterone receptor irrespective of the ligand used is found: norethisterone much less than levonorgestrel less than 3-keto-destogestrel less than gestodene. The difference between the various progestagens is significant with the exception of that between 3-keto-desogestrel and gestodene, when Org 2058 is used as ligand. For the cytosolic progesterone receptor, the same order is found with the exception that similar RBAs are found for gestodene and 3-keto-desogestrel. The four progestagens clearly differ with respect to binding to the androgen receptor using dihydrotestosterone as labelled ligand in intact cells; the ranking (low to high) is: norethisterone less than 3 keto-desogestrel less than levonorgestrel and gestodene. The difference between 3-keto-desogestrel and levonorgestrel or gestodene is significant. The selectivity indices (ratio of the mean RBA for the progesterone receptor to that of androgen receptor) in intact cells are significantly higher for 3-keto-desogestrel and gestodene than for levonorgestrel and norethisterone. From these results we conclude that the introduction of the 18-methyl in norethisterone (levonorgestel) increases both the binding to the progesterone and androgen receptors.

  7. Progesterone Induces Mucosal Immunity in a Rodent Model of Human Taeniosis by Taenia solium

    PubMed Central

    Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; Pérez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J.C.; Morales-Montor, Jorge

    2011-01-01

    More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders. PMID:22110394

  8. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.

    PubMed

    Souza, M F; Couto-Pereira, N S; Freese, L; Costa, P A; Caletti, G; Bisognin, K M; Nin, M S; Gomez, R; Barros, H M T

    2014-06-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  9. Dioestrous ovariectomy: a model to study the role of progesterone in the onset of canine pseudopregnancy.

    PubMed

    Gobello, C; Baschar, H; Castex, G; de la Sota, R L; Goya, R G

    2001-01-01

    It has been suggested that overt pseudopregnancy in bitches is caused by an increase in the concentration of serum prolactin as a result of an abrupt decrease in progesterone concentration in the late luteal phase. This hypothesis was tested by using ovariectomy at dioestrus as an experimental model. A total of 18 intact cross- and purebred bitches were used. Eleven animals were ovariectomized (day 0) between day 25 and day 40 of the oestrous cycle, and seven intact bitches were used as controls. Blood samples for determination of prolactin and progesterone concentrations were collected on days -1, 1, 2, 3 and 7 in the ovariectomized group, and on day 1 and day 7 in the control group. On day 7, the presence or absence of overt pseudopregnancy was recorded. The four ovariectomized bitches with a history of pseudopregnancy showed signs of overt pseudopregnancy (P < 0.01). On day 7, progesterone concentrations were significantly higher in the control than in the ovariectomized bitches (P < 0.01). The expected decrease in serum progesterone concentration after ovariectomy was similar in pseudopregnant bitches and non-pseudopregnant bitches. However, in pseudopregnant bitches, but not in non-pseudopregnant bitches, there was a marked increase (expressed as percentage change) in the concentration of prolactin between day -1 and day 7 (P < 0.01). It was concluded that the abrupt decrease in progesterone concentrations does not lead systematically to pseudopregnancy. Only in bitches predisposed to pseudopregnancy would an abrupt decrease in progesterone concentrations induce a substantial increase in prolactin concentrations, which in turn would trigger the typical signs of pseudopregnancy.

  10. Influence of different length spacers containing enzyme conjugate on functional parameters of progesterone ELISA.

    PubMed

    Shrivastav, Tulsidas G; Chaube, Shail K; Kariya, Kiran P; Prasad, Pramod K V; Kumar, Dinesh

    2013-01-01

    In steroid enzyme immunoassay (EIA), there is an increase or decrease of labeled steroid recognition by antibody due to homologous and heterologous combinations of enzyme conjugate with immunogen that affects sensitivity of the assay. We have introduced three to 18 atomic length linkers between enzyme and steroid moieties and studied their effects on functional parameters such as sensitivity, ED(50), and specificity of progesterone enzyme immunoassays. Progesterone-3-carboxymethyloxime-bovine serum albumin (P-3-CMO-BSA) was used as an immunogen to raise the antiserum in New Zealand white rabbits. Five enzyme conjugates were prepared using 17-α-hydroxy-progesterone-3-carboxymethyloxime (17-α-OH-P-3-CMO) as carboxylic derivative of 17-α-hydroxy-progesterone and horseradish peroxidase (HRP) as label. These were 17-α-OH-P-3-CMO-HRP, 17-α-OH-P-3-CMO-urea-HRP (17-α-OH-P-3-CMO-U-HRP), 17-α-OH-P-3-CMO-ehylenediamine-HRP (17-α-OH-P-3-CMO-EDA-HRP), 17-α-OH-P-3-CMO-carbohydrazide-HRP (17-α-OH-P-3-CMO-CH-HRP), and 17-α-OH-P-3-CMO-adipic acid dihydrazide-6-aminocaproic acid-HRP (17-α-OH-P-3-CMO-ADH-6ACA-HRP). The influence of different atomic length linkers on sensitivity, ED(50), and specificity were studied with reference to label without linker. The results of the present investigation revealed that the incorporation of ADH-6ACA spacer in 17-α-hydroxy-progesterone-enzyme conjugate improved the sensitivity in antigen plus bridge heterologous EIA system. The presence of spacer in enzyme conjugate improved the sensitivity and specificity (cross-reactivity) in some antigen plus bridge heterologous assay of progesterone. PMID:23323985

  11. Progesterone induces mucosal immunity in a rodent model of human taeniosis by Taenia solium.

    PubMed

    Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; Pérez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J C; Morales-Montor, Jorge

    2011-01-01

    More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders.

  12. Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function

    PubMed Central

    Franco, Heather L.; Rubel, Cory A.; Large, Michael J.; Wetendorf, Margeaux; Fernandez-Valdivia, Rodrigo; Jeong, Jae-Wook; Spencer, Thomas E.; Behringer, Richard R.; Lydon, John P.; DeMayo, Francesco J.

    2012-01-01

    The ovarian steroid progesterone, acting through the progesterone receptor (PR), coordinates endometrial epithelial-stromal cell communication, which is critical for its development and function. PR expression in these cellular compartments is under tight temporal and endocrine control. Although ex vivo studies demonstrated the importance of stromal PR expression, they failed to show a role for epithelial PR in uterine function. Here, the in vivo role of PR in the uterine epithelium is defined using floxed PR (PRf/f) mice crossed to Wnt7a-Cre mice. Progesterone was unable to stimulate the expression of its epithelial target genes, including Ihh, in the Wnt7a-Cre+PRf/− mice. Analysis was conducted on Ihh to determine whether PR directly regulates epithelial gene transcription. ChIP-on-chip analysis identified PR binding sites in the 5′-flanking region of Ihh. Cotransfection of the proximal Ihh promoter with PR demonstrated that PR directly regulates Ihh transcription. Female Wnt7a-Cre+PRf/− mice are infertile due to defects in embryo attachment, stromal cell decidualization, and the inability to cease estrogen-induced epithelial cell proliferation. Finally, progesterone was unable to inhibit neonatal endometrial glandular development in Wnt7a-Cre+PRf/− mice. Thus, epithelial PR is necessary for the regulation of progesterone epithelial target gene expression, as well as uterine function and development.—Franco, H. L., Rubel, C. A., Large, M. J., Wetendorf, M., Fernandez-Valdivia, R., Jeong, J.-W., Spencer, T. E., Behringer, R. R., Lydon, J. P., DeMayo, F. J. Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function. PMID:22155565

  13. Cerebrospinal Fluid Cortisol and Progesterone Profiles and Outcomes Prognostication after Severe Traumatic Brain Injury

    PubMed Central

    Santarsieri, Martina; Niyonkuru, Christian; McCullough, Emily H.; Dobos, Julie A.; Dixon, C. Edward; Berga, Sarah L.

    2014-01-01

    Abstract Despite significant advances in the management of head trauma, there remains a lack of pharmacological treatment options for traumatic brain injury (TBI). While progesterone clinical trials have shown promise, corticosteroid trials have failed. The purpose of this study was to (1) characterize endogenous cerebrospinal fluid (CSF) progesterone and cortisol levels after TBI, (2) determine relationships between CSF and serum profiles, and (3) assess the utility of these hormones as predictors of long-term outcomes. We evaluated 130 adults with severe TBI. Serum samples (n=538) and CSF samples (n=746) were collected for 6 days post-injury, analyzed for cortisol and progesterone, and compared with healthy controls (n=13). Hormone data were linked with clinical data, including Glasgow Outcome Scale (GOS) scores at 6 and 12 months. Group based trajectory (TRAJ) analysis was used to develop temporal hormone profiles delineating distinct subpopulations. Compared with controls, CSF cortisol levels were significantly and persistently elevated during the first week after TBI, and high CSF cortisol levels were associated with poor outcome. As a precursor to cortisol, progesterone mediated these effects. Serum and CSF levels for both cortisol and progesterone were strongly correlated after TBI relative to controls, possibly because of blood–brain barrier disruption. Also, differentially impaired hormone transport and metabolism mechanisms after TBI, potential de novo synthesis of steroids within the brain, and the complex interplay of cortisol and pro-inflammatory cytokines may explain these acute hormone profiles and, when taken together, may help shed light on why corticosteroid trials have previously failed and why progesterone treatment after TBI may be beneficial. PMID:24354775

  14. Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.

    PubMed

    Ioffe, Olga B; Zaino, Richard J; Mutter, George L

    2009-03-01

    Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other

  15. TBI and Sex: Crucial role of progesterone protecting the brain in an omega-3 deficient condition

    PubMed Central

    Tyagi, Ethika; Agrawal, Rahul; Ying, Zhe; Gomez-Pinilla, Fernando

    2014-01-01

    We assessed whether the protective action of progesterone on traumatic brain injury (TBI) could be influenced by the consumption of omega-3 fatty acids during early life. Pregnant Sprague Dawley rats were fed on omega-3 adequate or deficient diet from 3rd day of pregnancy and their female offspring were kept on the same diets up to the age of 15 weeks. Ovariectomy was performed at the age of 12 weeks to deprive animals from endogenous steroids until the time of a fluid percussion injury (FPI). Dietary n-3 fatty acid deficiency increased anxiety in sham animals and TBI aggravated the effects of the deficiency. Progesterone replacement counteracted the effects of TBI on the animals reared under n-3 deficiency. A similar pattern was observed for markers of membrane homeostasis such as 4-Hydroxynonenal (HNE) and secreted phospholipases A2 (sPLA2), synaptic plasticity such as brain derived neurotrophic factor (BDNF), syntaxin (STX)-3 and growth associated protein (GAP)-43, and for growth inhibitory molecules such as myelin-associated glycoprotein (MAG) and Nogo-A. Results that progesterone had no effects on sham n-3 deficient animals suggest that the availability of progesterone is essential under injury conditions. Progesterone treatment counteracted several parameters related to synaptic plasticity and membrane stability reduced by FPI and n-3 deficiency suggest potential targets for therapeutic applications. These results reveal the importance of n-3 preconditioning during early life and the efficacy of progesterone therapy during adulthood to counteract weaknesses in neuronal and behavioral plasticity. PMID:24361060

  16. Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced to swim.

    PubMed

    Molina-Hernández, M; Téllez-Alcántara, N P

    2001-07-01

    In rats, some behavioral changes occurring during pregnancy related to the presence of progesterone may be analyzed in the forced swimming task (FST), which is designed to test the antidepressant profile of drugs. The present study was aimed to analyze in pregnant rats, in rats after delivery, or in rats after receiving progesterone those behavioral changes displayed in the FST. We hypothesize that pregnancy and progesterone will produce antidepressant-like effects in rats forced to swim. Therefore, pregnant rats (14th, 17th, and 20th days), or rats after delivery (3rd, and 7th days) were tested in the FST. Ovariectomized rats receiving saline (0.9%; i.p.), clomipramine (1.25 mg/kg; i.p.), or desipramine (2.14 mg/kg; i.p.) for 28 days were also tested in the FST. In a second series of experiments, ovariectomized rats receiving vehicle or progesterone (0.5 mg/kg; or 2.0 mg/kg; sc.) were tested in the FST. Locomotion was evaluated in the open field test. Results showed that in the FST: 1) pregnancy (P < 0.05), or progesterone (P < 0.05), or desipramine (P < 0.05), reduced immobility by increasing climbing; 2) clomipramine (P < 0.05) reduced immobility by increasing swimming; 3) rats tested after delivery displayed similar behavior than control rats. A lower locomotion was observed only at the end of pregnancy. In conclusion, results suggest that during pregnancy, a reproductive process characterized by its high levels of progesterone, antidepressant-like effects can be found.

  17. Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows.

    PubMed

    Starbuck, G R; Mann, G E

    2010-04-01

    We have investigated the effects administering exogenous progesterone, via insertion of a controlled internal drug release (CIDR) for 4 days, from either day 5 or day 12 of the oestrous cycle on plasma oestradiol concentrations. In study 1, in which progesterone was administered from day 5, measurement of plasma oestradiol in daily samples revealed a significant (p < 0.001) decrease in peripheral oestradiol concentration. In contrast, in study 2, similar administration of progesterone from day 12 had no effect on plasma oestradiol concentration. In study 3, collection of hourly samples following progesterone treatment on day 5 revealed peak progesterone concentrations within 1 h of CIDR insertion and nadir oestradiol concentrations within 4 h. The results demonstrate that treatment with progesterone early in the luteal phase causes a rapid inhibition of oestradiol secretion, while later treatment does not. While improvements in pregnancy rate following progesterone treatment at this time have traditionally been attributed to increases in progesterone, the potential involvement of decreased oestradiol secretion has often been overlooked. PMID:19144035

  18. Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells

    PubMed Central

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis. PMID:27113901

  19. Endogenous and exogenous progesterone influence body temperature in dairy cows.

    PubMed

    Suthar, V S; Burfeind, O; Bonk, S; Dhami, A J; Heuwieser, W

    2012-05-01

    Three experiments were conducted to determine the effect of endogenous progesterone (P4) on body temperature comparing lactating, pregnant with lactating, nonpregnant cows, and to study the effect of exogenous P4 administered via a controlled internal drug release (CIDR) insert on body temperature in lactating dairy cows. Body temperature was measured vaginally and rectally using temperature loggers and a digital thermometer, respectively. In experiment 1, 10 cyclic lactating cows (3 primiparous, 7 multiparous) and 10 lactating, pregnant cows (3 primiparous, 7 multiparous) were included. Vaginal temperatures and serum P4 concentrations were greater in pregnant cows (vaginal: 0.3±0.01°C; P4: 5.5±0.4 ng/mL) compared with nonpregnant cows. In experiment 2, estrous cycles of 14 postpartum healthy, cyclic, lactating cows (10 primiparous, 4 multiparous) were synchronized, and cows were assigned randomly to 1 of 2 treatments (CIDR-P4 or CIDR-blank). A temperature logger was inserted 1 d after ovulation using a P4-free CIDR (CIDR-blank) and a CIDR containing 1.38g of P4 (CIDR-P4) in the control (n=7) and the P4-treated group (n=7), respectively. On d 3 after P4 treatment, vaginal temperature was 0.3±0.03°C greater compared with that on d 1 and d 5. In experiment 3, 9 cyclic multiparous lactating cows were enrolled 1±1 d after confirmed ovulation and a temperature logger inserted. Two days later, a CIDR-P4 was inserted on top of the CIDR-blank. On d 5±1 and d 7±1, respectively, the CIDR-P4 and CIDR-blank with the temperature logger were removed. During the CIDR-P4 treatment (48h), vaginal temperature was 0.2±0.05°C and 0.1±0.05°C greater than during the pre- and post-treatment periods (48h), respectively. Serum P4 concentration peaked during CIDR-P4 treatment (2.2±0.8 ng/mL) and was greater than during the pre-treatment period (0.2±0.2 ng/mL) for 48h. An increase in vaginal temperature could be due to endogenous and exogenous P4. However, a correlation between

  20. Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancer.

    PubMed

    Sinreih, Maša; Hevir, Neli; Rižner, Tea Lanišnik

    2013-02-25

    Endometrial cancer (EC) is one of the most common gynecological malignancies worldwide. It is associated with prolonged exposure to estrogens that is unopposed by the protective effects of progesterone, which suggests that altered progesterone biosynthesis, metabolism and actions might be implicated in the development of EC. Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium. First, we examined the expression of genes encoding proteins associated with progesterone biosynthesis: steroidogenic acute regulatory protein (STAR); a side chain cleavage enzyme (CYP11A1); and 3β-hydroxysteroid dehydrogenase/ketosteroid isomerase (HSD3B). There were 1.9- and 10.0-fold decreased expression of STAR and CYP11A1, respectively, in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and HSD3B2. Next, we examined expression of genes encoding five progesterone metabolizing enzymes: the 3-keto and 20-ketosteroid reductases (AKR1C1-AKR1C3) and 5α-reductases (SRD5A1 and SRD5A2); and the opposing 20α-hydroxysteroid dehydrogenase (HSD17B2). These genes are expressed in EC and adjacent control endometrium. No statistically significant differences were seen in mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1. Expression of HSD17B2 was 3.0-fold increased, and expression of SRD5A2 was 3.7-fold decreased, in EC versus adjacent control endometrium. We also examined mRNA levels of progesterone receptors A and B (PGR), and separately the expression of progesterone receptor B (PR-B). Here we saw 1.8- and 2.0-fold lower mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium. This down-regulation of STAR, CYP11A1 and PGR in endometrial cancer may lead to decreased progesterone biosynthesis and actions although the effects on progesterone levels should be further studied.

  1. Autoclaved, previously used intravaginal progesterone devices induces estrus and ovulation in anestrous Toggenburg goats.

    PubMed

    Souza, J M G; Torres, C A A; Maia, A L R S; Brandão, F Z; Bruschi, J H; Viana, J H M; E Oba; Fonseca, J F

    2011-11-01

    Intravaginal progesterone devices are used worldwide for estrus induction in goats. Reused devices are able to induce estrus; however, this can be a health risk within a flock. The objective was to compare new and previously used (and autoclaved) progesterone-releasing intravaginal devices for induction of estrus and ovulation in seasonally anestrous Toggenburg goats. Anestrous goats (n=42) received new intravaginal devices containing 0.3g progesterone (CONTROL), or similar devices previously used for either 6 (USED6) or 12d (USED12) and subsequently autoclaved. All goats received 5mg dinoprost at device insertion and 200 IU eCG 5d later, and all devices were removed after 6d. After device removal, estrus was monitored and females displaying signs of estrus were mated by fertile bucks. Transrectal ovarian ultrasonography was performed after device removal until detection of ovulation. Blood samples were collected for determination of plasma progesterone concentration at different times. There was no difference (P>0.05) among groups CONTROL, USED6 or USED12 for: estrus response (87, 100 or 100%, respectively); duration of estrus (32.3±2.3, 25.2±3.4 or 27.3±4.1h); ovulation rate (100, 88 or 100%); number of ovulations (1.5±0.2, 1.9±0.3 or 1.7±0.3); and pregnancy rate (60, 58 or 67%). Plasma progesterone (P4) concentrations were greater (P<0.05) in CONTROL than in USED6-treated and USED12-treated goats (7.2±1.2, 4.7±0.7 and 4.3±0.6 ng/mL, respectively) at 6h after device insertion; these differences were maintained until 4d after device insertion (3.4±0.4, 2.3±0.2, and 2.5±0.2 ng/mL). Overall, plasma progesterone concentrations were greater (P<0.05) in nulliparous than in lactating goats (3.1±0.8 compared to 2.4±0.6 ng/mL, respectively). In conclusion, autoclaved, previously used intravaginal progesterone-releasing devices resulted in significant lesser plasma progesterone concentrations than new devices, but were similarly effective in inducing estrus

  2. Progesterone modulates pro-inflammatory cytokine expression profile after spinal cord injury: Implications for neuropathic pain.

    PubMed

    Coronel, María F; Raggio, María C; Adler, Natalia S; De Nicola, Alejandro F; Labombarda, Florencia; González, Susana L

    2016-03-15

    Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. Glial cell activation and cytokine production contribute to the pathology of central neuropathic syndromes. In this study we evaluated the effects of progesterone, a neuroactive steroid, on pain development and the spinal expression of IL-1β, its receptors (IL-1RI and IL-1RII) and antagonist (IL-1ra), IL-6 and TNFα, and NR1 subunit of NMDAR. Our results show that progesterone, by modulating the expression of pro-inflammatory cytokines and neuronal IL-1RI/NR1 colocalization, emerges as a promising agent to prevent chronic pain after SCI.

  3. Unconjugated oestrogen and progesterone concentrations in the blood of bitches with false pregnancy and pyometra.

    PubMed

    Hadley, J C

    1975-06-21

    The changes in total unconjugated oestrogen and progesterone concentrations in the peripheral blood of one bitch throughout a false pregnancy were measured. The levels of these hormones detected in 11 bitches when examined during a false pregnancy, and in 13 other bitches with pyometa are also reported. Oestrogen and progesterone concentrations were within normal limits in both of these conditions where single samples were obtained, but the bitch with false pregnancy studied in detail showed a raised oestrogen level during metoestrus. The significance of these results is discussed in relation to previous studies on the aetiology of false pregnancy and pyometra.

  4. Characterization of progesterone profiles in fall-calving Norwegian Red cows.

    PubMed

    Garmo, R T; Martin, A D; Thuen, E; Havrevoll, Ø; Steinshamn, H; Prestløkken, E; Randby, A; Eknaes, M; Waldmann, A; Reksen, O

    2009-10-01

    Progesterone profiles in Norwegian Red cows were categorized, and associations between the occurrence of irregularities in the profiles and the commencement of luteal activity were investigated. The cows were managed in 3 feeding trials from 1994 to 2001 and from 2005 to 2008 at the Norwegian University of Life Sciences. The cows were followed from calving, and the milk samples collected represented 502 lactations from 302 cows. Milk samples for progesterone analysis were taken 3 times weekly from 1994 throughout 1998 and from 2005 to 2008 and 2 times weekly from 1999 to 2001. Commencement of luteal activity was defined as the first day of 2 consecutive measurements of progesterone concentration >or=3 ng/mL not earlier than 10 d after calving. Delayed ovulation type I was defined as consistently low progesterone concentration, <3 ng/mL for >or=50 d postpartum. Delayed ovulation type II was defined as prolonged interluteal interval with milk progesterone measurements <3 ng/mL for >or=12 d between 2 luteal phases. Persistent corpus luteum (PCL) type I was defined as delayed luteolysis with milk progesterone >or=3 ng/mL for >or=19 d during the first estrous cycle postpartum. Persistent corpus luteum type II was defined as delayed luteolysis with milk progesterone >or=3 ng/mL for >or=19 d during subsequent estrous cycles before first artificial insemination. Delayed ovulation type I was present in 14.7%, delayed ovulation type II in 2.8%, PCL type I in 6.7%, and PCL type II in 3.3% of the profiles. Commencement of luteal activity was related to milk yield, parity, PCL type I, and the summated occurrence of PCL type I and II. The least squares means for the interval to commencement of luteal activity were 24.2 d when PCL type I and II were present and 29.5 d when PCL type I and II were absent. The likelihood of pregnancy to first service was not affected in cows with a history of PCL when artificial insemination was carried out at progesterone concentrations <3 ng/mL (i

  5. Progesterone inhibits vascular remodeling and attenuates monocrotaline-induced pulmonary hypertension in estrogen-deficient rats.

    PubMed

    Tofovic, P S; Zhang, X; Petrusevska, G

    2009-07-01

    (Full text is available at http://www.manu.edu.mk/prilozi). Pulmonary arterial hypertension (PH) is predominantly a disease of young females. Yet, little is known regarding the effects of female sex hormones in PH. Female rats develop less severe PH compared to male rats, and ovariectomy (OVX) exacerbates PH. Although OVX rats treated with estradiol develop less severe disease, the role of progesterone in OVX-induced exacerbation of disease has not been examined. Progesterone was shown to dilate pulmonary vessels and to inhibit proliferation of endothelial and vascular smooth muscle cells. Therefore, we hypothesized that progesterone may confer protective effects in experimental PH. A total of 30 female rats were ovariectomized and OVX rats were randomly administered either saline (OVX-Control group, n = 7), monocrotaline (60mg/kg i.p.; OVX-MCT group; n = 12), or MCT plus progesterone (30microg/kg/h via osmotic minipumps; OVX-MCT+P group; n = 11). After 32 days animals were instrumented for in situ (open chest) measurements of right ventricle (RV) peak systolic (RVSP) and end diastolic (RVEDP) pressures, and tissue samples were obtained for morphometric and histological analysis. Administration of MCT elevated RVSP (22.2 +/- 1.1 vs. 46.7 +/- 2.4 mmHg) and RVEDP (1.51 +/- 0.86 vs. 11.9+/-2.2 mmHg), increased RV/left ventricle + septum (RV/LV+S) ratio (0.256 +/- 0.010 vs. 0.582 +/- 0.033, OVX vs. OVX-MCT), and induced media hypertrophy of small size pulmonary arteries. In ovariectomized pulmonary hypertensive rats, treatment with progesterone attenuated the severity of disease (OVX-MCT+P group: RVSP = 36.6 +/- 2.3 mmHg; RV/LV+S = 0.468 +/- 0.025; RVEDP = 7.5 +/-1.5 mmHg), attenuated vascular remodeling (media % index: 28.2 +/- 1.1 vs. 34.2 +/- 1.3), and reduced mortality (9% vs. 25%; OVX-MCT+P vs. OVX-MCT). This study provides the first evidence that in estrogen-deficient rats, progesterone has protective effects in MCT-induced PH. Further evaluation of the role of

  6. Progesterone modulates pro-inflammatory cytokine expression profile after spinal cord injury: Implications for neuropathic pain.

    PubMed

    Coronel, María F; Raggio, María C; Adler, Natalia S; De Nicola, Alejandro F; Labombarda, Florencia; González, Susana L

    2016-03-15

    Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. Glial cell activation and cytokine production contribute to the pathology of central neuropathic syndromes. In this study we evaluated the effects of progesterone, a neuroactive steroid, on pain development and the spinal expression of IL-1β, its receptors (IL-1RI and IL-1RII) and antagonist (IL-1ra), IL-6 and TNFα, and NR1 subunit of NMDAR. Our results show that progesterone, by modulating the expression of pro-inflammatory cytokines and neuronal IL-1RI/NR1 colocalization, emerges as a promising agent to prevent chronic pain after SCI. PMID:26943964

  7. Potential use of single measurement of serum progesterone in detecting early pregnancy failure.

    PubMed

    Hanita, O; Hanisah, A H

    2012-06-01

    Early pregnancy failure is a common pregnancy complication. In clinical practice, the time delay to distinguish viable from nonviable pregnancy is often distressing to patients and doctors. A highly sensitive and specific biomarker that accurately discriminates between viable and nonviable pregnancy would be useful for early intervention. Progesterone has been shown as a biomarker of early pregnancy failure. However the usefulness is still questionable due to the different cutoff values used. A study was conducted to determine the role of progesterone as a marker of early pregnancy failure and to establish the cut-off value in discriminating between viable and nonviable pregnancy. The study was carried out in the Obstetric and Gynecology Patient Admission Centre (OBPAC), Universiti Kebangsaan Malaysia Medical Centre (UKMMC) for a period of twelve months. Ninety-five pregnant women of 13 weeks or less period of amenorrhoea (POA) were recruited. Fourteen normal pregnant women were controls. The patients with early pregnancy failure were classified according to types of abortion. Single measurement of serum progesterone was carried out during admission. The outcome of pregnancy was followed up until 22 weeks of POA to ascertain viability of the fetus. Median progesterone levels were significantly lower in women with nonviable pregnancies compared with viable pregnancy [10.7ng/ml (0.60-49.80) vs. 45.9ng/ml (15.40-127.20) respectively, p<0.001]. Progesterone levels were also significantly lower in threatened abortion patients with outcomes of nonviable pregnancy compared with pregnancies that progressed on to the viability period [23.3 +/- 12.0 vs. 89.7 +/- 33.2 respectively, p<0.001]. At cut-off value of 32.7ng/ ml, progesterone had 90% sensitivity with 75% negative predictive value and 92% specificity with 97% positive predictive value. The area under curve for progesterone was 0.95 (95% Confidence Interval, 0.903-0.990). In conclusion, these findings indicate that

  8. Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome

    PubMed Central

    Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie

    2016-01-01

    Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS. PMID:27386819

  9. Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome.

    PubMed

    Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie

    2016-07-08

    Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS.

  10. Sensory mechanisms involved in the induction of pseudopregnancy by progesterone: increased sensitivity to stimulation of the pudendal sensory field.

    PubMed

    Luque, E H; Castro-Vazquez, A

    1983-07-01

    The sensory mechanisms that participate in the induction of pseudopregnancy after a single injection of progesterone were investigated. Unless otherwise indicated, rats were kept in group cages and vaginal smears were taken daily. Progesterone evoked pseudopregnancy in a dose-dependent manner when administered to proestrous or estrous rats that received no cervicovaginal stimulation. The probability of pseudopregnancy after progesterone was higher on estrus. Cervicovaginal stimulation of proestrous rats that received 5 mg progesterone 10 h before was performed with a rod with a sliding stop attached to regulate its intravaginal penetration. Progesterone facilitated responsiveness to this stimulus, although the amount injected was not significantly effective in increasing the incidence of pseudopregnancy in nonstimulated rats. However, the mere application of the stop of the stimulator on the perineal skin was followed by a significantly higher incidence of pseudopregnancy in progesterone-injected rats than in their vehicle-injected controls, which suggested an action of the steroid on perineal sensitivity. Accordingly, the pseudopregnancy-evoking effect of progesterone was clearly inhibited by refraining from taking vaginal smears for 5 days after steroid injection on estrus. No further inhibition was observed after isolating the animals in single rat cages. However, daily finger stimulation of the perineal skin of nonsmeared rats restored to a normal level response to progesterone. Furthermore, this response was severely impaired by transecting the pudendal nerves before the injection. It is concluded that pseudopregnancy is induced in progesterone-treated rats through sensory stimulation of the pudendal receptive field and it is suggested that the pudendal nerve may subserve as a secondary afferent system to elicit the pseudopregnancy response. The possibility progesterone also acts on other afferent systems including the main afferent system constituted by the

  11. Effect of postnatal progesterone therapy following preterm birth on neurosteroid concentrations and cerebellar myelination in guinea pigs.

    PubMed

    Palliser, H K; Kelleher, M A; Tolcos, M; Walker, D W; Hirst, J J

    2015-08-01

    Allopregnanolone protects the fetal brain and promotes normal development including myelination. Preterm birth results in the early separation of the infant from the placenta and consequently a decline in blood and brain allopregnanolone concentrations. Progesterone therapy may increase allopregnanolone and lead to improved oligodendrocyte maturation. The objectives of this study were to examine the efficacy of progesterone replacement in augmenting allopregnanolone concentrations during the postnatal period and to assess the effect on cerebellar myelination - a region with significant postnatal development. Preterm guinea pig neonates delivered at 62 days of gestation by caesarean section received daily s.c. injections of vehicle (2-Hydroxypropyl-β-cyclodextrin) or progesterone (16 mg/kg) for 8 days until term-equivalent age (TEA). Term delivered controls (PND1) received vehicle. Neonatal condition/wellbeing was scored, and salivary progesterone was sampled over the postnatal period. Brain and plasma allopregnanolone concentrations were measured by radioimmunoassay; cortisol and progesterone concentrations were determined by enzyme immunoassay; and myelin basic protein (MBP), proteolipid protein (PLP), oligodendroctye transcription factor 2 (OLIG2) and platelet-derived growth factor receptor-α (PDGFRα) were quantified by immunohistochemistry and western blot. Brain allopregnanolone concentrations were increased in progesterone-treated neonates. Plasma progesterone and cortisol concentrations were elevated in progesterone-treated male neonates. Progesterone treatment decreased MBP and PLP in lobule X of the cerebellum and total cerebellar OLIG2 and PDGFRα in males but not females at TEA compared with term animals. We conclude that progesterone treatment increases brain allopregnanolone concentrations, but also increases cortisol levels in males, which may disrupt developmental processes. Consideration should be given to the use of non-metabolizable neurosteroid

  12. Luteal phase support with estradiol and progesterone versus progesterone alone in GnRH antagonist ICSI cycles: a randomized controlled study.

    PubMed

    Ismail Madkour, Wael A; Noah, Bassel; Abdel Hamid, Amr M S; Zaheer, Hena; Al-Bahr, Awatif; Shaeer, Mahmoud; Moawad, Ashraf

    2016-06-01

    In vitro fertilization (IVF) cycles are associated with a defective luteal phase. Although progesterone supplementation to treat this problem is standard practice, estrogen addition is debatable. Our aim was to compare pregnancy outcomes in 220 patients undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles protocol. The patients were randomly assigned into two equal groups to receive either vaginal progesterone alone (90 mg once daily) starting on the day of oocyte retrieval for up to 12 weeks if pregnancy occurred or estradiol addition (2 mg twice daily) starting on the same day and continuing up to seven weeks (foetal viability scan). Primary outcomes were pregnancy and ongoing pregnancy rates per embryo transfer. Secondary outcomes were implantation and early pregnancy loss rates. Pregnancy rates showed no significant difference between group 1 (39.09%) and 2 (43.63%) (p value = 0.3). Similarly, both groups were comparable regarding ongoing pregnancy rate (32.7% group 1 and 36.3% group 2, p value = 0.1). Implantation rates showed no difference between group 1 (19.25%) and group 2 (23.44%) (p value = 0.2). Early pregnancy loss rates were comparable, with 6.3% and 7.2% in groups 1 and 2, respectively, (p value = 0.4). In conclusion, the addition of 4 mg estrogen daily to progesterone for luteal support in antagonist ICSI cycles is not beneficial for pregnancy outcome. PMID:27434094

  13. A similar 5'-flanking region is required for estrogen and progesterone induction of ovalbumin gene expression.

    PubMed

    Dean, D C; Gope, R; Knoll, B J; Riser, M E; O'Malley, B W

    1984-08-25

    We have previously transferred an ovalbumin-beta-globin fusion gene (ovalglobin) into primary cultures of chick oviduct cells and demonstrated that an ovalbumin gene 5'-flanking sequence between -221 and -95 is necessary for progesterone-mediated transcriptional induction (Dean, D. C., Knoll, B. J., Riser, M. E., and O'Malley, B. W. (1983) Nature (Lond.) 305, 551-554). Here we compare 5'-flanking sequences required for induction of the ovalglobin gene by 17 beta-estradiol and progesterone. The early gene of simian virus 40 was inserted into the same plasmid as the ovalbumin fusion gene to serve as an internal control. Since transcription of the viral early gene was unaffected by the presence of steroid hormone or deletions in the ovalbumin gene 5'-flanking region, the level of its transcripts could be monitored as a reference standard for ovalglobin transcription. Ovalglobin transcripts initiated principally from the ovalbumin cap site in the presence or absence of progesterone and 17 beta-estradiol. Deletion of 5'-flanking sequences to -197 had little effect on the induction with either hormone, while successive deletions to -180, -161, and -143 resulted in a gradual decrease in the level of induction. Deletion to -95 eliminated the induction. The results of this study indicate that DNA control elements for regulation of the ovalbumin gene by estrogen and progesterone either overlap directly or are clustered in close proximity in the 5'-flanking region near the ovalbumin gene promoter. PMID:6088508

  14. STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

    PubMed

    Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang

    2016-06-08

    Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.

  15. Environmental gestagens activate fathead minnow (Pimephales promelas) nuclear progesterone and androgen receptors in vitro

    EPA Science Inventory

    Gestagen is a collective term for endogenous and synthetic progesterone receptor (PR) ligands. In teleost fishes, 17á,20â-dihydroxy-4-pregnen-3-one (DHP) and17á,20â,21- trihydroxy-4-pregnen-3-one (20â-S) are the predominant progestogens, whereas in other vertebrates the major pro...

  16. Diagnostic Efficacy of a Single Progesterone Determination to Assess Full-Term Pregnancy in the Bitch.

    PubMed

    Rota, A; Charles, C; Starvaggi Cucuzza, A; Pregel, P

    2015-12-01

    In clinical settings, when the reproductive history of a near-term bitch is limited to mating dates, the possibility to accurately assess whether pregnancy is at term could be very useful in order to be able to plan a correct management of parturition or to safely perform an elective Caesarean section. The aim of this study was to assess the diagnostic efficacy of a single progesterone determination, measured by chemiluminescent immunoassay (CLIA), in predicting the occurrence of parturition on the following day. At least one blood sample was collected from 51 pre-partum bitches during the 3 days before parturition and on day of parturition. The efficacy of progesterone as a marker of the end of pregnancy was tested using a receiver operating characteristic (ROC) analysis. Youden's index was calculated to select the optimal cut-off value (with 95% confidence interval), aiming at maximizing the correct identification of negative events, so not to risk to diagnose as full term a bitch which is not. Progesterone concentration lower than 3.4 ng/ml correctly identified the bitches whelping the following day; however, because of the obliged prudential approach, sensitivity was low (46.88%), and 17 of 32 full-term bitches were missed. Due to a very large individual variation, a single progesterone determination has low diagnostic efficacy, although it can represent a useful first screening. PMID:26510871

  17. Inhibition of progesterone secretion by a 3 beta-hydroxysteroid dehydrogenase inhibitor in pregnant goats.

    PubMed

    Taylor, M J

    1987-06-01

    Epostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase, was administered to goats in late pregnancy in the presence or absence of concurrent treatment with prostaglandin synthetase inhibitors (indomethacin and diclofenac sodium) and the effect on steroidogenesis in the corpus luteum and adrenal cortex determined by measurement of peripheral concentrations of progesterone and cortisol respectively. Concentrations of both steroids were reduced to about 20% of pretreatment levels within 6 h of epostane administration. Cortisol concentrations subsequently increased about 24 h after epostane administration and returned to and exceeded pretreatment values, but progesterone concentrations remained suppressed until premature delivery, which occurred in all animals 44 +/- 2 h (mean +/- S.E.M.) after epostane administration. However, combined administration of epostane and prostaglandin synthetase inhibitor prevented the onset of labour in the majority of animals, but progesterone secretion in animals receiving this combined treatment did not differ from that in animals given epostane alone. It is concluded that progesterone withdrawal is an important component of the mechanisms which initiate parturition in the goat and that increased prostaglandin synthesis is essential for delivery in this species, but perhaps not for luteolysis. PMID:3625098

  18. Estrous behavior, progesterone in peripheral plasma and milk in dairy goats at onset of breeding season.

    PubMed

    Thibier, M; Pothelet, D; Jeanguyot, N; De Montigny, G

    1981-03-01

    Two large flocks of 60 and 120 French Alpine dairy does were studied beginning in late June. Estrous behavior was checked daily in the presence of bucks, and numerous blood and milk samples were collected. The end of the anestrus was characterized by consistent low progesterone around .1 ng/ml in plasma and 2 to 4 ng/ml in milk. Cyclic activity was detected in early July in one flock and in early August in the other. Individual patterns of plasma and milk progesterone in cyclic females were correlated greater than .5. Estrus was short (4 to 5 days) in 3 to 10 goats sampled daily following first estrus, and a small and transient rise of concentrations of progesterone was concomitant. Mean plasma and milk progesterone increased from about .1 to .5 and 2 to 4 ng/ml at the time of estrus to 6 to 8 in plasma and 6 to 10 ng/ml in milk 10 days later (midluteal phase). Twenty-one days after mating, concentrations in plasma and milk of pregnant animals were of the same magnitude as during the midluteal phase and higher than those in nonpregnant does (.1 to .7 and 2 to 3 ng/ml in plasma and milk). PMID:7196414

  19. Oestrus synchronisation and fertility in black Bengal goats following administration of progesterone/prostaglandin and gonadotrophins.

    PubMed

    Ishwar, A K; Pandey, J N

    1992-03-01

    Oestrus synchronisation, fertility and kidding behaviour were studied in 44 Black Bengal goats. They were divided into six experimental groups: group 1, control; group 2, progesterone; group 3, progesterone, pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG); group 4, prostaglandin F2 alpha (PGF2 alpha); group 5, PGF2 alpha, PMSG and HCG; group 6, PMSG and HCG. There was 100 per cent synchronisation of oestrus in the groups treated with progesterone, progesterone with PMSG and HCG, and prostaglandin with PMSG and HCG. In the other two treated groups the synchronisation was between 66 and 75 per cent. In the control group only 50 per cent of the animals came into oestrus during the period of observation. The duration of oestrus varied between 19 and 24 hours except in group 5 where it was 40.87 hours. Animals came on heat between 95 and 137 hours after treatment except in group 5 where the interval was only 18.87 hours. A maximum fertility of 75 per cent was observed in group 4 while the kidding percentage was greatest in group 2. There appeared to be no beneficial effect of superovulation on the number of kids produced. Gestation length was similar in all the groups. PMID:1585072

  20. Evaluation of dimethoate-induced implantation delay and nidation by progesterone in albino mice.

    PubMed

    Mahadevaswami, M P; Kaliwal, B B

    2003-01-01

    We investigated the effect of dimethoate, an organophosphorus insecticide, and progesterone on implantation. Virgin pregnant albino mice received dimethoate orally at a dose of 28 mg/kg body wt/d from days 1 to 7. Laparotomy on day 8 showed no implantation sites. Thereafter, graded doses of progesterone, 4, 9, and 12 mg/kg body wt/d, were administered up to day 15. A group of control mice received a similar quantity of distilled water. Autopsy on day 8 revealed that the control mice were pregnant, with a normal number of implantations and 8.08% pre-implantation loss, whereas treatment with dimethoate for 7 days or with dimethoate for 7 days followed by progesterone for 8 days totally abolished implantation, with a 100% pre-implantation loss. In all treated mice, a significant decrease occurred in body weight gain, as well as in the weight of the ovaries, uterus, and liver when compared with those of control mice. No significant changes were found in other organ weights (kidneys, adrenals, spleen, thymus, or thyroid). The observed effect of dimethoate could be due to an imbalance in the estrogen-progesterone ratio essential for implantation. Alternatively, dimethoate treatment could result in blastotoxicity or have an impact on the hypothalamic-pituitary axis.

  1. The adrenal gland and progesterone stimulates testicular steroidogenesis in the rat in vivo.

    PubMed

    Feek, C M; Tuzi, N L; Edwards, C R

    1989-04-01

    Administration of pharmacological doses of glucocorticoid to male rats in vivo suppresses adrenal steroidogenesis and inhibits testicular steroidogenesis by inhibiting the anterior pituitary secretion of LH. In contrast, administration of ACTH to these pharmacologically-suppressed rats stimulates the adrenal secretion of progesterone and testicular steroidogenesis. The mechanism by which ACTH increases testicular steroidogenesis is dependent on the presence of the adrenal gland and is reproduced by the administration of progesterone. The conclusion from these data is that the adrenal gland has an important role in generating external signals that modulate the hypothalamic-pituitary-gonadal axis in male rats. The adrenal secretion of glucocorticoid acts as a negative signal to testicular steroidogenesis whereas progesterone acts as a positive signal. The adrenal secretion of progesterone and its conversion to testosterone by steroidogenic enzymes in the cytoplasm of the Leydig cell may provide an alternative pathway for testosterone biosynthesis and may account for the increased plasma testosterone levels during the acute phase of stress and mating.

  2. Salivary Progesterone Is Associated with Reduced Coherence of Attentional, Cognitive, and Motivational Systems

    ERIC Educational Resources Information Center

    Schultheiss, Oliver C.; Patalakh, Mariya; Rosch, Andreas G.

    2012-01-01

    The present study tested whether the hypothesis that high levels of progesterone (P) have a decoupling effect on the function of the brain hemispheres (Hausmann & Gunturkun, 2000) also extends to attentional functions, referential connections between verbal and nonverbal representations and the degree to which implicit motivational needs match a…

  3. Abiraterone Treatment in Castration-Resistant Prostate Cancer Selects for Progesterone Responsive Mutant Androgen Receptors

    PubMed Central

    Chen, Eddy J.; Sowalsky, Adam G.; Gao, Shuai; Cai, Changmeng; Voznesensky, Olga; Schaefer, Rachel; Loda, Massimo; True, Lawrence D.; Ye, Huihui; Troncoso, Patricia; Lis, Rosina L.; Kantoff, Philip W.; Montgomery, Robert B.; Nelson, Peter S.; Bubley, Glenn J.; Balk, Steven P.; Taplin, Mary-Ellen

    2014-01-01

    Purpose The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can activate certain mutant androgen receptors (ARs) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone activated mutant ARs. Experimental Design AR was examined by targeted sequencing in metastatic tumor biopsies from 18 CRPC patients who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone. Results The progesterone-activated T878A mutant AR was present at high allele frequency in 3 of the 18 CRPC cases. It was also present in one focus of resistant tumor in the neoadjuvant treated patient, but not in a second clonally related resistant focus which instead had lost one copy of PTEN and both copies of CHD1. The T878A mutation appeared to be less common in the subset of CRPC patients treated with abiraterone plus dutasteride, and transfection studies showed that dutasteride was a more potent direct antagonist of the T878A versus the wildtype AR. Conclusions These findings indicate that selection for tumor cells expressing progesterone-activated mutant ARs is a mechanism of resistance to CYP17A1 inhibition. PMID:25320358

  4. Evidence for a single steroid-binding protein in the rabbit progesterone receptor.

    PubMed

    Lamb, D J; Kima, P E; Bullock, D W

    1986-10-01

    The rabbit uterine progesterone receptor copurifies as two molecular weight (Mr) forms of about 105,000 and 78,000. To investigate whether these are different proteins, we have used protease digestion, reversible denaturation, and photoaffinity labeling in studies on the steroid-binding domain of the receptor. Digestion of the Mr 105,000 and 78,000 forms, photoaffinity labeled with [3H]R5020, with Staphylococcus aureus V8 protease revealed identical peptide fragments of Mr 43,000, 39,000, and 27,000-30,000. When receptor in cytosol was denatured, separated by electrophoresis, and then reconstituted, [3H]progesterone bound specifically to a single form at about Mr 105,000. After partial purification, the reversible denaturation procedure revealed both the larger and the smaller progesterone-binding species similar to the photoaffinity-labeled species in this preparation. Receptor in uterine cytosol prepared under mild conditions appeared as a predominant large molecular weight form on photoaffinity labeling with [17 alpha-methyl-3H]R5020, [6,7-3H]R5020, or [3H]RU27987. Further purification of this cytosol showed the generation of a smaller labeled species. These results from three different approaches reinforce the view that the rabbit progesterone receptor contains a single steroid-binding protein.

  5. Cloning, pharmacological characterization and expression analysis of Atlantic cod (Gadus morhua, L.) nuclear progesterone receptor.

    PubMed

    Chen, Shi X; Almeida, Fernanda F L; Andersson, Eva; Taranger, Geir Lasse; Schmidt, Ruben; Schulz, Rüdiger W; Bogerd, Jan

    2012-10-01

    To better understand the role(s) of progesterone in fish spermatogenesis, we cloned the nuclear progesterone receptor (Pgr) of Atlantic cod. The open-reading frame of the cod pgr consists of 2076 bp, coding for a 691-amino acids-long protein that shows the highest similarity with other piscine Pgr proteins. Functional characterization of the receptor expressed in mammalian cells revealed that the cod Pgr exhibited progesterone-specific, dose-dependent induction of reporter gene expression, with 17α,20β-dihydroxy-4-pregnen-3-one (DHP), a typical piscine progesterone, showing the highest potency in activating the receptor. During ontogenesis, the pgr mRNA was undetectable in embryo's 24 h after fertilization, but became detectable 4 days after fertilization. During the larval stage, the expression levels increased steadily with the development of the larvae. In adult fish, pgr was predominantly expressed in gonads of both sexes. During the onset of puberty, testicular pgr transcript levels started to increase during rapid spermatogonial proliferation, and peaked when spermiation started. In situ hybridization studies using testis tissue during the rapid growth phase containing all germ cell stages indicated that in cod, pgr mRNA is predominantly located in Sertoli cells that are in contact with proliferating spermatogonia. Taken together, our data suggests that the Pgr is involved in mediating progestagen stimulation of the mitotic expansion of spermatogonia, and in processes associated with the spermiation/spawning period in Atlantic cod. PMID:22885560

  6. Comparison of intravaginal progesterone gel and intramuscular 17-α-hydroxyprogesterone caproate in luteal phase support

    PubMed Central

    SATIR, FUNDA; TOPTAS, TAYFUN; INEL, MURAT; ERMAN-AKAR, MUNIRE; TASKIN, OMUR

    2013-01-01

    The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total β-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28–3.03; P=0.002; and OR, 1.66; 95% CI, 1.07–2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00–3.41; P=0.05; and OR, 1.43, 95% CI, 0.89–2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes. PMID:23837065

  7. Progesterone regulates the proliferation of breast cancer cells - in vitro evidence.

    PubMed

    Azeez, Juberiya M; Sithul, Hima; Hariharan, Indhu; Sreekumar, Sreeja; Prabhakar, Jem; Sreeja, Sreeharshan; Pillai, Madhavan Radhakrishna

    2015-01-01

    Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival. PMID:26609221

  8. Progesterone regulates the proliferation of breast cancer cells – in vitro evidence

    PubMed Central

    Azeez, Juberiya M; Sithul, Hima; Hariharan, Indhu; Sreekumar, Sreeja; Prabhakar, Jem; Sreeja, Sreeharshan; Pillai, Madhavan Radhakrishna

    2015-01-01

    Reports state that surgery performed at different phases of the menstrual cycle may significantly affect breast cancer treatment outcome. From previous studies, we identified differentially expressed genes in each menstrual cycle phase by microarray, then subjected them to functional in vitro analyses. Microarray studies disclosed genes that are upregulated in the luteal phase and follicular phase. TOB-1 is a tumor suppressor gene and was expressed exclusively in the luteal phase in our microarray study. Therefore, we further functionally characterized the protein product of TOB-1 in vitro. To our knowledge, no studies have yet been conducted on reactive oxygen species-regulated tumor suppressor interactions in accordance with the biphasic nature of progesterone. This work demonstrates that progesterone can produce reactive oxygen species in MCF-7 cells and that TOB-1 exerts a series of non-genomic interactions that regulate antiproliferative activity by modulating the antioxidant enzyme superoxide dismutase. Furthermore, this study implicates PTEN as an interacting partner for TOB-1, which may regulate the downstream expression of cell cycle control protein p27 via multiple downstream signaling pathways of progesterone through a progesterone receptor, purely in a time- and concentration-dependent manner. These results support the hypothesis that surgery conducted during the luteal phase of the menstrual cycle may facilitate improved patient survival. PMID:26609221

  9. Progesterone, oestradiol-17 beta and LH during the oestrous cycle of muskoxen (Ovibos moschatus).

    PubMed

    Rowell, J E; Flood, P F

    1988-09-01

    Progesterone, oestradiol-17 beta and LH were measured in plasma from 6 non-pregnant, captive, female muskoxen during the 1984 and 1985 breeding seasons. Jugular blood samples were taken on an alternating 3/4-day schedule in 1984 and daily or at 4-h intervals over oestrus, via indwelling jugular cannulae, for 6 weeks in 1985. Oestrous cycle length was 19.6 +/- 0.96 (s.d.) days (n = 19) and did not vary between the first and subsequent cycles of the season. Progesterone was lowest at oestrus (less than or equal to 0.1 ng/ml), began to rise on Days 4-5, peaked on Days 10-12 (mean = 2.6 ng/ml) and returned to baseline 2-5 days before the next oestrus. A small rise in progesterone before the first cycle of the breeding season was observed on 7 of 12 occasions. Oestradiol-17 beta was significantly higher (P less than 0.001) 1-4 days before, or coincident with, oestrus. The average duration of the LH peak was 24.6 h (n = 7) and coincided with observations of behavioural oestrus. In one animal behavioural oestrus and an LH peak preceded a small progesterone rise at the beginning of the breeding season. The temporal relationship of these three hormones during the muskox oestrous cycle is very similar to that seen in domestic ruminants. PMID:3184036

  10. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

    PubMed Central

    Malik, Sonia

    2016-01-01

    Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce ‘secretory’ changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering ‘therapeutic compliance’ with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in ‘Real world’ clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic. PMID:27042538

  11. Effects of estrogen and progesterone on spatial memory consolidation in aged females.

    PubMed

    Harburger, Lauren L; Bennett, Jennifer C; Frick, Karyn M

    2007-04-01

    Interpretation of data illustrating that estrogen, with or without progestin, is detrimental to memory in post-menopausal women is complicated by the fact that little is known about the effects of progestins on memory. The present study examined if estrogen, alone or with progesterone, affects spatial memory consolidation in ovariectomized aged female mice. Mice received eight training trials in a spatial Morris water maze followed immediately by injection of water-soluble 17beta-estradiol (E(2); 0.2 mg/kg) or vehicle. Mice were re-tested 24 h later. All mice learned to find the platform on Day 1. On Day 2, the performance of control, but not E(2) mice, deteriorated, suggesting that E(2) enhanced memory for the platform location. In a second experiment, mice were injected with E(2) and 10 or 20 mg/kg water-soluble progesterone. The 10 mg/kg dose of progesterone did not affect estrogen's ability to enhance spatial memory consolidation, but 20 mg/kg blocked this effect. These data indicate that estrogen can improve spatial memory consolidation in aged females and that this effect can be attenuated by progesterone.

  12. Distribution and regulation by estrogen of progesterone receptor in the hypothalamus of the cat.

    PubMed

    Bayliss, D A; Seroogy, K B; Millhorn, D E

    1991-05-01

    The diencephalon is critically involved in the estrogen-dependent receptor-mediated stimulation of respiration by progesterone in cats. To identify a neuroanatomic basis for this effect of progesterone, the diencephalon of the ovariectomized cat was examined immunohistochemically with an antiprogesterone receptor (anti-PR) monoclonal antibody. No immunostaining was found in ovariectomized animals pretreated with sesame oil alone. In contrast, numerous cells in the ventromedial aspect of the hypothalamus from cats pretreated with estradiol benzoate were PR immunoreactive. Thus, PR is induced by estrogen in hypothalamic neurons of cats. In animals pretreated with estradiol benzoate, the highest density of immunostained neurons was found throughout the infundibular nucleus, especially in the region of the mammillary recess of the third ventricle. PR-immunoreactive cells were also distributed throughout the periventricular nucleus, with the highest density located rostrally and immediately above the suprachiasmatic nucleus. Notably and in contrast to a number of other species (e.g. rat and guinea pig), only very few weakly stained PR-containing cells were found in the hypothalamic ventromedial nucleus. This latter finding could reflect the progesterone independence of sexual behaviors in cat. Overall, we have identified hypothalamic areas that may subserve estrogen-dependent receptor-mediated effects of progesterone in the cat, such as the stimulation of respiration. PMID:2019267

  13. Elevated yolk progesterone moderates prenatal heart rate and postnatal auditory learning in bobwhite quail (Colinus virginianus).

    PubMed

    Herrington, Joshua A; Rodriguez, Yvette; Lickliter, Robert

    2016-09-01

    Previous studies have established that yolk hormones of maternal origin can influence physiology and behavior in birds. However, few studies have examined the effects of maternal gestagens, like progesterone, on chick behavior and physiology. We tested the effects of experimentally elevated egg yolk progesterone on embryonic heart rate and postnatal auditory learning in bobwhite quail hatchlings. Quail chicks were passively exposed to an individual maternal assembly call for 10 min/hr during the 24 hr following hatching. Preference for the familiarized call was tested at 48 hr following hatching in three experimental groups: chicks that received artificially elevated yolk progesterone (P) prior to incubation, vehicle-only controls (V), and non-manipulated controls (C). Resting heart rate of P, V, and C embryos were also measured on prenatal day 17. The resting heart rate of P embryos was significantly higher than both the V and C embryos. Chicks from the P group also showed an enhanced preference for the familiarized bobwhite maternal call when compared to chicks from the C and V groups. Our results indicate that elevated yolk progesterone in pre-incubated bobwhite quail eggs can influence arousal level in bobwhite embryos and postnatal perceptual learning in bobwhite neonates. PMID:27108924

  14. STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells

    PubMed Central

    Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang

    2016-01-01

    Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS. PMID:27270953

  15. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization

    PubMed Central

    Baker, Valerie L.; Jones, Christopher A.; Doody, Kevin; Foulk, Russell; Yee, Bill; Adamson, G. David; Cometti, Barbara; DeVane, Gary; Hubert, Gary; Trevisan, Silvia; Hoehler, Fred; Jones, Clarence; Soules, Michael

    2014-01-01

    STUDY QUESTION Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex®) non-inferior to vaginal progesterone (Endometrin®) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of −2.8% (95% confidence interval (CI) −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18–42 years, with a BMI of ≤30 kg/m2, with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2–3) FSH of ≤15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS®). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Using a PP analysis

  16. Relation between progesterone concentrations during the early luteal phase and follicular dynamics in goats.

    PubMed

    Menchaca, Alejo; Rubianes, Edgardo

    2002-03-15

    We studied the relationship between progesterone (P4) concentrations early in the estrus cycle and follicular dynamics in dairy goats. We used seven untreated goats (control group) and six progesterone treated goats (P group) with a controlled internal drug release device from Days 0 to 5 (Day 0: day of ovulation). We performed daily ultrasonograph during the interovulatory interval to determine ovarian change and took daily blood samples to determine serum estradiol 17beta (E2) and P4 concentrations by RIA. We divided the control goats into 3- (n = 4) and 4-wave goats (n = 3), according to the number of follicular waves recorded during the ovulatory cycle. Mean progesterone concentrations between Days I and 5 were higher and mean estradiol concentrations between Days 3 and 5 were lower in 4-wave goats (P4: 3.8+/-0.2 ng/ml; E2: 1.6+/-0.2 pg/ml) than in 3-wave goats (P4: 2.0+/-0.5 ng/ml, P < 0.05; E2: 4.4+/-0.9 pg/ml, P < 0.05). Wave 2 emerged earlier in 4-wave (Day 4.2+/-0.3) than in 3-wave goats (Day 7.3+/-0.3, P < 0.05). Three out of six of the progesterone-treated goats had short cycles (mean 8.0+/-0.0 days) and ovulated from Wave 1. The other three goats had shorter cycles (mean 18.3+/-0.3 days) than the control group (20.0+/-0.2 days; P < 0.05), although they were within the normal range of control cycles (shortened cycles). In the three treated goats with shortened cycles (two with four waves, one with three waves), mean progesterone concentrations between Days I and 5 were higher (4.7+/-0.6 ng/ml) than in the 3-wave control goats. In these goats, Wave 2 emerged at Day 4.3+/-0.3, similar to the time observed in 4-wave goats but earlier (P < or = 0.05) than in 3-wave control goats. Overall results confirm a relationship between the progesterone levels and the follicular wave turnover during the early luteal phase in the goat. Higher progesterone concentrations may accelerate follicular turnover probably by an early decline of the negative feedback action of

  17. Altered folate metabolism modifies cell proliferation and progesterone secretion in human placental choriocarcinoma JEG-3 cells.

    PubMed

    Moussa, Carolyne; Ross, Nikia; Jolette, Philippe; MacFarlane, Amanda J

    2015-09-28

    Folate is an essential B vitamin required for de novo purine and thymidylate synthesis, and for the remethylation of homocysteine to form methionine. Folate deficiency has been associated with placenta-related pregnancy complications, as have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). We aimed to determine the effect of altered folate metabolism on placental cell proliferation, viability and invasive capacity and on progesterone and human chorionic gonadotropin (hCG) secretion. Human placental choriocarcinoma (JEG-3) cells cultured in low folic acid (FA) (2 nM) demonstrated 13% (P<0.001) and 26% (P<0.001) lower proliferation, 5.5% (P=0.025) and 7.5% (P=0.004) lower invasion capacity, and 5 to 7.5% (P=0.004-0.025) lower viability compared with control (20 nM) or supplemented (100 nM) cells, respectively. FA concentration had no effect on progesterone or hCG secretion. Small interfering RNA (siRNA) knockdown of MTR gene and protein expression resulted in 17.7% (P<0.0001) lower proliferation and 61% (P=0.014) higher progesterone secretion, but had no effect on cell invasion and hCG secretion. siRNA knockdown of MTHFD1 gene expression in the absence of detectable changes in protein expression resulted in 10.3% (P=0.001) lower cell proliferation, but had no effect on cell invasion and progesterone or hCG secretion. Our data indicate that impaired folate metabolism can result in lower trophoblast proliferation, and could alter viability, invasion capacity and progesterone secretion, which may explain in part the observed associations between folate and placenta-related complications.

  18. The influence of estrogen and progesterone on parasympathetic vasodilatation in the rat submandibular gland.

    PubMed

    Smith, Joshua; Lindsay, Michael; Rahimian, Roshanak; Anderson, Leigh

    2009-03-12

    Previous studies suggest that NO- and PGI(2)-independent pathways play a greater role in parasympathetic vasodilatation in the submandibular glands (SMG) of female than of male rats. Thus, the purpose of this study was to determine whether estrogen and progesterone influence the relative contributions of NO and PGI(2) to parasympathetic vasodilatation in the SMG. Vascular responses to chorda-lingual nerve stimulation were examined in sham-operated (SHAM) and ovariectomized (OVX) female rats and in OVX rats treated with either 17beta-estradiol alone or a combination of 17beta-estradiol and progesterone. Compared with SHAM animals, increases in vascular conductance in OVX rats were reduced at 1, 2 and 5 Hz (p<0.05). Blood flow responses in OVX+17beta-estradiol and OVX+17beta-estradiol+progesterone rats were indistinguishable from those observed in SHAM animals. Indomethacin had no effect on vasodilatation in SHAM and OVX+17beta-estradiol rats, but increased vascular responses in OVX animals (p<0.02). The addition of L-NAME resulted in a significant reduction in vasodilatation at all frequencies. In OVX rats treated with both estrogen and progesterone, indomethacin caused a reduction in vasodilatation and L-NAME further diminished the remaining responses. Under all conditions, vasodilatation was due largely, if not exclusively, to direct parasympathetic rather than antidromic sensory nerve activation. Finally, both neuronally-derived and endothelium-derived NO appeared to be responsible for the NO-dependent vasodilatation, but endothelium-derived NO became increasingly important as the frequency of stimulation increased. We conclude that estrogen and progesterone influence parasympathetic vasodilatation through combined effects on NO-, PGI(2)- and non-NO/PGI(2)-mediated pathways.

  19. A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix

    PubMed Central

    Romero, Roberto; Yeo, Lami; Miranda, Jezid; Hassan, Sonia; Conde-Agudelo, Agustin; Chaiworapongsa, Tinnakorn

    2014-01-01

    Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two-thirds of preterm births occur after the spontaneous onset of labor, and the remaining one-third after “indicated” preterm birth; however, the causes of spontaneous preterm labor and “indicated” preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identified in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at <33 weeks of gestation by 44%, along with the rate of admission to the neonatal intensive care unit, respiratory distress syndrome, requirement for mechanical ventilation, and a composite score of neonatal morbidity/mortality. There is no evidence that 17-alpha-hydroxyprogesterone caproate can reduce the rate of preterm delivery in women with a short cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (<25mm). PMID:23314512

  20. Effects of estrogens and progesterone on the synaptic organization of the hypothalamic ventromedial nucleus.

    PubMed

    Sá, S I; Lukoyanova, E; Madeira, M D

    2009-08-18

    The majority of the studies on the actions of estrogens in the ventrolateral part of the hypothalamic ventromedial nucleus (VMNvl) concern the factors that modulate the receptive component of the feminine sexual behavior and the expression of molecular markers of neuronal activation. To further our understanding of the factors that regulate synaptic plasticity in the female VMNvl, we have examined the effects of estradiol and progesterone, and of estrogen receptor (ER) subtype selective ligands on the number of dendritic and spine synapses established by individual VMNvl neurons and on sexual behavior. In contrast to earlier studies that analyzed synapse densities, our results show that exogenous estradiol increases the number of spine as well as of dendritic synapses, irrespective of the dose and regimen of administration. They also reveal that an effective dose of estradiol administered as one single pulse induces the formation of more synapses than the same dose administered as two pulses on consecutive days. Our results further show that both ER subtypes are involved in the mediation of the synaptogenic effects of estrogens on VMNvl neurons since the administration of the selective ERalpha, propyl-pyrazole-triol (PPT), and ERbeta, diarylpropionitrile (DPN), agonists induced a significant increase in the number of synapses that, however, was more exuberant for PPT. Despite its relevant role in feminine sexual behavior, progesterone had no synaptogenic effect in the VMNvl as no changes in synapse numbers were noticed in rats treated with progesterone alone, with estradiol followed by progesterone or with the antiprogestin mifepristone (RU486). Except for the sequential administration of estradiol and progesterone, none of the regimens was associated with lordosis response to vaginocervical stimulation. Therefore, from the sex steroids that undergo cyclic variations over the estrous cycle, only estrogens, acting through both ERalpha and ERbeta, play a key role in

  1. Thyroxin and progesterone concentrations in pregnant, nonpregnant bitches, and bitches during abortion.

    PubMed

    Thuróczy, Julianna; Müller, Linda; Kollár, Eszter; Balogh, Lajos

    2016-04-01

    Serum progesterone and thyroxin concentrations were measured weekly until 61 to 62 days after ovulation in 24 pregnant bitches and in the control group of nine nonpregnant bitches in the luteal phase. Fourteen of the 24 dogs had a normal pregnancy and parturition. Ten of the 24 dogs showed mucinous or colored vaginal discharge, decreased appetite, or lethargy. These initial signs of abortion or fetal resorption were noted during the fourth week of pregnancy, and the process occurred over the next 2 weeks. Progesterone and thyroxin concentrations were measured by quantitative ELISAs validated to dog serum. The serum progesterone concentrations of the group going through abortions differed significantly from the third week until the end of the eighth week. The mean serum thyroxin concentrations of healthy pregnant and nonpregnant groups significantly exceeded the reference range (20-45 nmol/L). The serum thyroxin concentrations in the abortion group were between 16.15 ± 3.17 and 40.78 ± 8.97 nmol/L. The values in this group were significantly different from the other two groups at the third week of the luteal phase. Clinical signs of abortion or fetus resorption manifested in midpregnancy. The clinical signs of abortion coincided in each case with a low serum progesterone concentration (<10 ng/mL). This phenomenon indicated, in contrast with other studies, that the decrease of serum progesterone below 10 ng/mL at the fourth week of pregnancy may signal impending abortion. In the second half of pregnancy, the thyroid gland was not able to respond adequately to the elevated requirement in thyroid hormone, although in other periods of the ovarian cycle, there were no clinical signs of hypothyroidism. PMID:26733120

  2. Progesterone metabolism by the hypothalamus, pituitary, and uterus of the rat during pregnancy

    SciTech Connect

    Marrone, B.L.; Karavolas, H.J.

    1981-07-01

    Metabolites of (/sup 3/H)progesterone were quantitated from incubations of hypothalamus, pituitary, and uterus of rats during different stages of pregnancy. The hypothalamus, anterior pituitary, and a section of uterus from five rats on Days 1, 8, 15, and 21 of pregnancy were incubated individually with (3H)progesterone and analyzed for metabolite formation by reverse isotopic dilution analysis. The radioactive metabolites present were 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one, 20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. The major metabolite formed by the hypothalamus and pituitary was 5 alpha-DHP. In the pituitary samples, formation of 5 alpha-DHP was decreased on Days 15 and 21 of pregnancy compared to Day 1, and formation of 20 alpha-hydroxy-5 alpha-pregnan-3-one was decreased on Day 21 compared to Day 1. In the uterine samples, 3 alpha-hydroxy-5 alpha-pregnan-20-one was the major metabolite formed at all stages of pregnancy. The formation of all metabolic products of progesterone by the uterus was increased on Day 21 compared to Days 1, 8, and 15 of pregnancy. No changes in the formation of progesterone metabolites were observed in the hypothalamic samples during pregnancy. It is concluded that there are different profiles in the in vitro metabolism of (3H)progesterone by the hypothalamus, pituitary, and uterus of the rat during the course of pregnancy.

  3. Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone

    PubMed Central

    Azboy, İbrahim; Özkaya, Mustafa; Demir, Teyfik; Demirtaş, Abdullah; Kağan Arslan, Arslan; Özkul, Emin; Akcan, Adnan; Tolunay, Tolga

    2016-01-01

    Introduction: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats’ bone. Methods: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham-operated group and a control group (water was given), estradiol treated group (17-β estradiol 0.015 mg/kg per day), genistein treated group (genistein 10 mg/kg per day), and an estradiol/progesterone combination group (17-β estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day). The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. Results: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. Conclusions: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis. PMID:27194109

  4. Uterine involution and progesterone level during the postpartum period in Barbary ewes in north Libya.

    PubMed

    Medan, M S; El-Daek, T

    2015-01-01

    The objectives of the present study were to determine the time of uterine involution and ovarian activity using ultrasound examination and progesterone assay. Weekly progesterone levels were measured starting one week postpartum until two weeks after the 1(st) postpartum estrus in Barbary ewes lambed during winter in AL-Bayda city, north of Libya. A total of 15 Barbary ewes were used in the present study distributed in three groups according to the month of lambing as group 1 (lambed in January), group 2 (lambed in February) and group 3 (lambed in March). Ewes were examined weekly by trans-rectal ultrasound to check involution of the uterus starting one week after lambing until complete uterine involution. Blood samples were collected from the jugular vein, and serum was separated and stored at -20 °C until measuring progesterone using ELISA. Results showed that uterine involution completed at day 35 postpartum in groups 1 and 2, while it occurred at day 28 in group 3. The mean progesterone level was basal (less than 1 ng/ml) for a long period and started to increase at days 119, 99 and 77 postpartum in group 1, 2 and 3, respectively. One ewe did not show estrus at all during the period of study in group 2 and there were no growing follicles on their ovaries. The obtained results indicate that, uterine involution as determined by ultrasound completed earlier in ewes lambed in March than those lambed in February or January. Also, progesterone level and ultrasound examination showed that there was no ovarian activity for a longtime after parturition indicating that reproduction in Barbary ewes tends to be seasonal in AL-Bayda city, north Libya.

  5. Uterine involution and progesterone level during the postpartum period in Barbary ewes in north Libya

    PubMed Central

    Medan, M.S.; EL-Daek, T.

    2015-01-01

    The objectives of the present study were to determine the time of uterine involution and ovarian activity using ultrasound examination and progesterone assay. Weekly progesterone levels were measured starting one week postpartum until two weeks after the 1st postpartum estrus in Barbary ewes lambed during winter in AL-Bayda city, north of Libya. A total of 15 Barbary ewes were used in the present study distributed in three groups according to the month of lambing as group 1 (lambed in January), group 2 (lambed in February) and group 3 (lambed in March). Ewes were examined weekly by trans-rectal ultrasound to check involution of the uterus starting one week after lambing until complete uterine involution. Blood samples were collected from the jugular vein, and serum was separated and stored at -20 °C until measuring progesterone using ELISA. Results showed that uterine involution completed at day 35 postpartum in groups 1 and 2, while it occurred at day 28 in group 3. The mean progesterone level was basal (less than 1 ng/ml) for a long period and started to increase at days 119, 99 and 77 postpartum in group 1, 2 and 3, respectively. One ewe did not show estrus at all during the period of study in group 2 and there were no growing follicles on their ovaries. The obtained results indicate that, uterine involution as determined by ultrasound completed earlier in ewes lambed in March than those lambed in February or January. Also, progesterone level and ultrasound examination showed that there was no ovarian activity for a longtime after parturition indicating that reproduction in Barbary ewes tends to be seasonal in AL-Bayda city, north Libya. PMID:26623357

  6. Simple and rapid solid-phase radioimmunoassay for serum progesterone, using the protein A of Staphylococcus aureus as immunoadsorbent

    SciTech Connect

    Jungers, J.; Delogne-Desnoeck, J.; Robyn, C.

    1981-07-01

    A simple, rapid, and inexpensive radioimmunoassay method for serum progesterone is described, which uses a solid-phase technique for separation of antibody-bound from antibody-free progesterone. Rabbit antiprogesterone immunoglobulins are adsorbed on the protein A of formaldehyde- and heat-treated Staphylococcus aureus cells (Pansorbin; Calbiochem-Behring Corp., La Jolla, California). The suspension of antibody-coated Pansorbin retains all its binding activity of 1-2-H(N)-progesterone when kept at + 4/sup 0/ or at -25/sup 0/C for at least 4 months. Dose-response curves obtained with ether-serum extracts and with the progesterone standard do not deviate significantly from parallelism. The progesterone standard gives identical dose-response curves whether diluted in the assay buffer or in a progesterone-free ether-serum extract. The sensitivity of the assay is 0.02 ng/assay tube. The intra-assay variation coefficient is 16%, and the routine interassay variation coefficient is 17%. The mean serum progesterone concentrations were 0.55 ng/ml during the follicular phase of the menstrual cycle and 12.5 ng/ml during the luteal phase. The average blank value for distilled water was 0.02 ng/assay tube.

  7. Interaction of estradiol, testosterone, and progesterone in the modulation of hormone-dependent aggression in the female rat.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1992-10-01

    Female rats that had become aggressive as a result of cohabiting with a sterile male were ovariectomized and implanted with Silastic tubes of estradiol, testosterone, and progesterone, estradiol and testosterone alone, or with empty tubes. The implants were designed to model serum concentrations present during the last week of pregnancy (estradiol, 0.06 ng/ml; testosterone, 2.6 ng/ml; progesterone, 70 ng/ml). Following a test of aggression 1 week postoperatively, estradiol and testosterone implants were replaced with ones designed to maintain the lower hormone levels present following parturition (0.02 ng/ml; 0.6 ng/ml, respectively). Progesterone was not replaced. At the first aggression test, females with estradiol and testosterone alone displayed significantly more aggression than females with these hormones plus progesterone. Both groups were more aggressive than females without hormone replacement. Following the exchange of large implants for small ones, females that previously had progesterone increased in aggression while females that previously had only estradiol and testosterone decreased in aggression. Both groups continued to be more aggressive than the group without hormone replacement. High serum progesterone present near the end of pregnancy appears to moderate the expression of aggression supported by estradiol and testosterone. Conversely, progesterone's decline at parturition appears to produce a rebound facilitation of aggression even though serum estradiol and testosterone simultaneously decline.

  8. Pregnancy-associated plasma protein A up-regulated by progesterone promotes adhesion and proliferation of trophoblastic cells.

    PubMed

    Wang, Jiao; Liu, Shuai; Qin, Hua-Min; Zhao, Yue; Wang, Xiao-Qi; Yan, Qiu

    2014-01-01

    Embryo implantation and development is a complex biological process for the establishment of the successful pregnancy. Progesterone is a critical factor in the regulation of embryo adhesion to uterine endometrium and proliferation. Although it has been reported that pregnancy-associated plasma protein A (PAPPA) is increased in pregnant women, the relationship between progesterone and PAPPA, and the effects of PAPPA on embryo adhesion and proliferation are still not clear. The present results showed that the serum level of progesterone and PAPPA was closely correlated by ELISA assay (p<0.01). PAPPA was detected in the villi of early embryo by RT-PCR, Western blot, immunohistochemistry and immunofluorescent staining. Moreover, PAPPA was significantly up-regulated by progesterone in trophoblastic (JAR) cells by Real-time PCR and ELISA assay (p<0.01); while the expression was decreased by the progesterone receptor inhibitor RU486. The down-regulation of PAPPA by siRNA transfection or up-regulation of PAPPA by progesterone treatment significantly decreased or increased the adhesion rate of trophoblastic cells to human uterine epithelial cell lines (RL95-2 and HEC-1A), respectively (p<0.01), as well as the proliferation of trophoblastic cells. In conclusion, PAPPA is up-regulated by progesterone, which promotes the adhesion and proliferation potential of trophoblastic cells. PMID:24817938

  9. Progesterone for hot flush and night sweat treatment--effectiveness for severe vasomotor symptoms and lack of withdrawal rebound.

    PubMed

    Prior, Jerilynn C; Hitchcock, Christine L

    2012-10-01

    A controlled trial recently showed that oral micronized progesterone (Progesterone, 300 mg at h.s. daily) was effective for vasomotor symptoms (VMS) in 133 healthy early postmenopausal women. Here, we present subgroup data in women with severe VMS (50 VMS of moderate-severe intensity/wk) and also 1-mo withdrawal study outcomes. Women with severe VMS (n = 46) resembled the full cohort but experienced 10 VMS/d of 3 of 4 intensity. On therapy, the progesterone VMS number (#) decreased significantly more than placebo # to 5.5/day (d) versus 8/d (ANCOVA -2.0 95% CI: -3.5 to -0.4). Just after trial mid-point, a withdrawal substudy (D/C) was added--56 women were invited and 34 (61%) took part (progesterone 17; placebo 17). Those in the D/C cohort resembled the whole cohort. On stopping, VMS gradually increased--at D/C week 4, on progesterone, VMS daily # reached 78% and significantly less than baseline (-3.0 to -0.8) but placebo VMS # did not differ from run-in. In summary, progesterone is effective for severe VMS and does not cause a rebound increase in VMS when stopped. That progesterone may be used alone for severe VMS and unlike estrogen does not appear to cause a withdrawal rebound increases VMS treatment options.

  10. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

    2015-02-01

    Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments. PMID:25715250

  11. Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.

    PubMed

    Yuan, Xiao-Hua; Fan, Yang-Yang; Yang, Chun-Rong; Gao, Xiao-Rui; Zhang, Li-Li; Hu, Ying; Wang, Ya-Qin; Jun, Hu

    2016-01-01

    The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal.

  12. Progesterone-dependent sexual behavior and protein patterns in the ventromedial hypothalamus of the adult female rat

    SciTech Connect

    Montemayor, M.E.; Roy, E.J.; Giometti, C.S.; Taylor, J.

    1994-09-01

    Controversy exists concerning mechanisms by which progesterone exerts central nervous system effects on behavior. Progesterone may affect behavior by genomic regulation of protein synthesis. Alternatively, it may work through non-genomic mechanisms, consistent with its short latency to act. Recent work suggests that progesterone may elicit its effects on sexual behavior by more than one mechanism in a tissue specific manner. In the present study, we have examined whether progesterone facilitation of sexual behavior is correlated with modification of protein synthesis patterns in the ventromedial hypothalamus (VMH). Ovariectomized rats were divided into three groups: estradiol (4 ug/ka at 0 and 18 hrs), estradiol (at 0 and 18 hrs) plus progesterone (2 mg/kg at 37 hrs), and vehicle only. {sup 35}S-labeled cysteine and methionine were bilaterally infused into the VMH at 37 hrs (the time of progesterone administration). Following 4 hrs of infusion, animals were tested for sexual behavior and sacrificed. Newly synthesized VMH proteins were separated by two dimensional gel electrophoresis followed by fluorography. Analysis of approximately 660 spots/fluorogram in two independent replications indicated that no protein was completely induced or lost as a result of being treated with progesterone. The abundances of several proteins were significantly altered in response to progesterone treatment in each replication; however, none were changed in abundance in both replications. These findings present no evidence that progesterone causes detectable alterations in VIMH protein patterns between 10-100 kDa in the 4.8-6.7 apparent pI range.

  13. Estrogen and progesterone differentially regulate carbonic anhydrase II, III, IX, XII, and XIII in ovariectomized rat uteri.

    PubMed

    Karim, Kamarulzaman; Giribabu, Nelli; Muniandy, Sekaran; Salleh, Naguib

    2016-01-01

    Changes in the uterus expression of carbonic anhydrase (CA) II, III, IX, XII, and XIII were investigated under the influence of sex-steroids in order to elucidate mechanisms underlying differential effects of these hormones on uterine pH. Uteri of ovariectomised rats receiving over three days either vehicle, estrogen, or progesterone or three days estrogen followed by three days either vehicle or progesterone were harvested. Messenger RNA (mRNA) and protein levels were quantified by real-time PCR and Western blotting, respectively. The distribution of CA isoenzymes proteins were examined by immunohistochemistry. The levels of CAII, III, XII, and XIII mRNAs and proteins were elevated while levels of CAIX mRNA and protein were reduced following progesterone-only and estrogen plus progesterone treatment, compared to the control and estrogen plus vehicle, respectively. Following estrogen treatment, expression of CAII, IX, XII, and CAXIII mRNAs and proteins were reduced, but remained at a level higher than control, except for CAIX, where its level was higher than the control and following progesterone treatment. Under progesterone-only and estrogen plus progesterone influences, high levels of CAII, III, XII, and XIII were observed in uterine lumenal and glandular epithelia and myometrium. However, a high level of CAIX was observed only under the influence of estrogen at the similar locations. In conclusion, high expression of CAII, III, XII, and XIII under the influence of progesterone and estrogen plus progesterone could result in the reduction of uterine tissue and fluid pH; however, the significance of high levels of CAIX expression under the influence of estrogen remains unclear. PMID:26709452

  14. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

    2015-02-01

    Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.

  15. High progesterone levels in women with high ovarian response do not affect clinical outcomes: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response. Methods We performed a retrospective cohort study that included 2850 women classified as high responders. The women were subdivided into six groups depending on their progesterone concentration on the day of human chorionic gonadotropin (hCG) administration: <0.5 ng/ml (1.81 ng/ml (>p90). Ovarian response was classified as high when > =20 oocytes were retrieved or when estradiol was > =3000 pg/ml. Clinical outcomes of each subgroup were analyzed. We also examined data from frozen-thawed embryo transfers. Results were analyzed with Student’s t- test to compare continuous variables and chi-squared test to compare proportions. A p-value of < =0.05 was considered statistically significant. Results The progesterone concentration increased with ovarian response, and elevated progesterone did not show a significant clinical impact on implantation rate and pregnancy rates. These data provide evidence that progesterone levels higher than 1.8 ng/ml do not have detrimental effect on oocyte quality or endometrial receptivity. Conclusions These data allow us to conclude that high progesterone levels correlate significantly with high estradiol levels and that in high responder women; progesterone levels do not show a significant clinical impact on results. PMID:25064138

  16. The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha-treated anestrous goats.

    PubMed

    Husein, Mustafa Q; Ababneh, Mohammed M; Haddad, Serhan G

    2005-01-01

    The objective of this experiment was to determine the effect of a 5-day progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive performance of anestrous goats. Thirty-six Mountain Black goats were randomly assigned in a 2 x 2 factorial arrangement and were administered intravaginally on day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100 microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which the goats in the CGPE and GPE groups were administered 300 IU eCG injections and those in CGP and GP groups were administered the control solution. The goats were exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h intervals for 72 h. Blood samples were collected from all goats for progesterone analysis. Progesterone concentrations increased only in CGPE and CGP during the period of device insertion but remained low in GPE and GP groups (P < 0.001). Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/- 0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0 progesterone concentrations differed (P < 0.05) among groups and were significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE or between CGP and GP groups. The number of goats ovulating based upon elevated progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9) and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration on day 0 and none of the goats with basal progesterone levels became pregnant. Pregnancy and kidding rates, twinning percentage and the number of kids born per goat exposed were

  17. Results of planned in-vitro fertilization programming through the pre-administration of the oestrogen-progesterone combined pill.

    PubMed

    Cohen, J; Debache, C; Solal, P; Serkine, A M; Achard, B; Boujenah, A; Pez, J P; Paris, X; Robert, J; Loffredo, V

    1987-01-01

    The use of an oestrogen-progesterone combined pill permits the induction of ovulation in the absence of any developing follicle. Two treatments were compared. In the first, patients received no prior treatment before stimulation. In the second, combined oestrogen-progesterone treatment was given during approximately two menstrual cycles prior to stimulation. No differences between the two groups were found in relation to oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Fewer luteinizing hormone surges occurred in patients pre-treated with steroids. The utilization of the oestrogen-progesterone combined pill prior to induction of ovulation facilitates the forward planning of patients for in-vitro fertilization. PMID:3106405

  18. The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha-treated anestrous goats.

    PubMed

    Husein, Mustafa Q; Ababneh, Mohammed M; Haddad, Serhan G

    2005-01-01

    The objective of this experiment was to determine the effect of a 5-day progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive performance of anestrous goats. Thirty-six Mountain Black goats were randomly assigned in a 2 x 2 factorial arrangement and were administered intravaginally on day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100 microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which the goats in the CGPE and GPE groups were administered 300 IU eCG injections and those in CGP and GP groups were administered the control solution. The goats were exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h intervals for 72 h. Blood samples were collected from all goats for progesterone analysis. Progesterone concentrations increased only in CGPE and CGP during the period of device insertion but remained low in GPE and GP groups (P < 0.001). Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/- 0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0 progesterone concentrations differed (P < 0.05) among groups and were significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE or between CGP and GP groups. The number of goats ovulating based upon elevated progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9) and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration on day 0 and none of the goats with basal progesterone levels became pregnant. Pregnancy and kidding rates, twinning percentage and the number of kids born per goat exposed were

  19. Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux: design, synthesis, characterization and biological evaluation.

    PubMed

    Zeinyeh, Waël; Mahiout, Zahia; Radix, Sylvie; Lomberget, Thierry; Dumoulin, Axel; Barret, Roland; Grenot, Catherine; Rocheblave, Luc; Matera, Eva-Laure; Dumontet, Charles; Walchshofer, Nadia

    2012-10-01

    Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.

  20. Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: analysis with zinc finger mutants and the progesterone antagonist ZK98299.

    PubMed Central

    Takimoto, G S; Tasset, D M; Eppert, A C; Horwitz, K B

    1992-01-01

    Human progesterone receptors (hPRs) are phosphorylated at multiple serine residues, first in a basal step and then in a hormone-induced step. To determine whether hormone-induced phosphorylation precedes or follows the interaction of hPRs with DNA two strategies were used. (i) DNA binding was prevented or altered with site-specific mutants of the A form of hPR; (ii) DNA binding of wild-type hPR forms A and B was prevented with the progesterone antagonist ZK98299. Two hPRA mutants were constructed: DBDCys, which lacks a critical cysteine residue in the first zinc finger, and DBDsp, which is mutated at three discriminatory amino acids to change its DNA binding specificity from a progesterone response element to an estrogen response element. Receptors were transiently expressed in PR-negative cells and were intranuclear. DBDCys did not bind DNA in vitro and DBDsp bound only the estrogen response element. Transiently expressed hPRA and DBDsp showed the upward shift in electrophoretic mobility characteristic of hormone-induced phosphorylation; it was absent with DBDCys. Hormone-induced [32P] orthophosphate incorporation into transiently expressed DBDCys was reduced 60% compared to hPRA and DBDsp but was not eliminated. ZK98299 binds hPRs but prevents their interaction with DNA. Compared to R5020, the antagonist reduced phosphorylation of hPRB and hPRA in T47D breast cancer cells by 60% and totally prevented the mobility shift. We conclude that the hormone-induced phosphorylation of hPR includes DNA-independent and DNA-dependent stages and that only DNA-dependent sites contribute to the mobility shift. Images PMID:1557412

  1. Cloning and initial characterization of nuclear and four membrane progesterone receptors in the fathead minnow(Pimephales promelas)

    EPA Science Inventory

    Both native progestagens and synthetic progestins have important effects on reproduction that are mediated through progesterone receptors (PRs). Progestagens regulate gamete maturation in vertebrates, are critical regulators of placental mammal pregnancy, and act as reproductive ...

  2. [Involvement of gap junctions in stimulation of in vitro maturation of the common frog oocytes by low progesterone concentrations].

    PubMed

    Skoblina, M N

    2004-01-01

    The inhibitor of gap junctions 18alpha-glycerretinic acid inhibits the maturation of follicle-enclosed common frog oocytes stimulated by low progesterone concentrations. The inhibitory effect of 18alpha-glycerretinic acid does not depend on concentrations within the limits of 5-40 microM. The inhibitory progesterone concentrations differ markedly in different females. The inhibitory effects of actinomycin D (5 microg/ml) and 18alpha-glycerretinic acid (5 microg/ml) were expressed when the same progesterone concentrations were used. When injected in an intact oocyte, Lucifer yellow was transported into the follicle cells, thus suggesting the presence of gap junction between these latter and the oocyte. The data obtained suggest that the previously described transcription-dependent factor formed in the follicle cells under the influence of low progesterone concentrations and stimulating oocyte maturation is transported in the oocyte along gap junctions.

  3. Effect of cytochrome P450 and aldo-keto reductase inhibitors on progesterone inactivation in primary bovine hepatic cell cultures.

    PubMed

    Lemley, C O; Wilson, M E

    2010-10-01

    Progesterone is required for maintenance of pregnancy, and peripheral concentrations of progesterone are affected by both production and inactivation. Hepatic cytochrome P450 (EC 1.14.14.1) and aldo-keto reductase (EC 1.1.1.145-151) enzymes play a pivotal role in the first step of steroid inactivation, which involves the addition of hydroxyl groups to various sites of the cyclopentanoperhydrophenanthrene nucleus. The current objective was to discern the proportional involvement of hepatic progesterone inactivating enzymes on progesterone decay using specific enzyme inhibitors. Ticlopidine, diltiazem, curcumin, dicumarol, and naproxen were used because of their selective inhibition of cytochrome P450s, aldo-keto reductases, and glucuronosyltransferases. Liver biopsies were collected from 6 lactating Holstein dairy cows, and cells were dissociated using a nonperfusion technique. Confluent wells were preincubated for 4 h with enzyme inhibitor and then challenged with progesterone for 1 h. Cell viability was unaffected by inhibitor treatment and averaged 84±1%. In control wells, 50% of the progesterone had been inactivated after a 1-h challenge with 5 ng/mL of progesterone. Preincubation with curcumin, ticlopidine, or naproxen caused the greatest reduction in progesterone inactivation compared with controls and averaged 77, 39, or 37%, respectively. Hydroxylation of 4-nitrophenol to 4-nitrocatechol in intact cells was inhibited by approximately 65% after treatment with curcumin or ticlopidine. Glucuronidation of phenol red or 4-nitrocatechol in intact cells was inhibited by treatment with curcumin, dicumarol, or naproxen. In cytoplasmic preparations, aldo-keto reductase 1C activity was inhibited by curcumin, dicumarol, or naproxen treatment. Microsomal cytochrome P450 2C activity was inhibited by treatment with curcumin or ticlopidine, whereas cytochrome P450 3A activity was inhibited by treatment with curcumin or diltiazem. The contribution of cytochrome P450 2C and

  4. Correlation analysis of the progesterone-induced sperm acrosome reaction rate and the fertilisation rate in vitro.

    PubMed

    Jiang, T; Qin, Y; Ye, T; Wang, Y; Pan, J; Zhu, Y; Duan, L; Li, K; Teng, X

    2015-10-01

    In this study, we aimed to investigate whether progesterone-induced acrosome reaction (AR) rate could be an indicator for fertilisation rate in vitro. Twenty-six couples with unexplained infertility and undergoing in vitro fertilisation (IVF) treatment were involved. On the oocytes retrieval day after routine IVF, residual sperm samples were collected to receive progesterone induction (progesterone group) or not (control group). AR rate was calculated and fertilisation rate was recorded. The correlation between progesterone-induced AR and fertilisation rate and between sperm normal morphology and 3PN (tripronuclear) were analysed using the Spearman correlation analysis. The AR rate of progesterone group was statistically higher than that of the control group (15.6 ± 5.88% versus 9.66 ± 5.771%, P < 0.05), but not significantly correlated with fertilisation rate (r = -0.053, P > 0.01) or rate of high-quality embryo development (r = -0.055, P > 0.01). Normal sperm morphology also showed no significant correlation with the amount of 3PN zygotes (r = 0.029, P > 0.01), rate of 3PN zygotes production (r = 0.20, P > 0.01), rate of 3PN embryo development (r = -0.406, P > 0.01), fertilisation rate (r = -0.148, P > 0.01) or progesterone-induced AR rate (r = 0.214, P > 0.01). Progesterone can induce AR in vitro significantly; however, the progesterone-induced AR may not be used to indicate fertilisation rate.

  5. Dermatophyte-hormone relationships: characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum.

    PubMed Central

    Clemons, K V; Schär, G; Stover, E P; Feldman, D; Stevens, D A

    1988-01-01

    We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. Progesterone is also an effective inhibitor of growth of the fungus. We report here studies which characterize more fully the specific binding properties and the functional responses of T. mentagrophytes and taxonomically related fungi to a series of mammalian steroid hormones. Scatchard analysis of [3H]progesterone binding in both the + and - mating types of Arthroderma benhamiae and in Microsporum canis revealed a single class of binding sites with approximately the same affinity as that in T. mentagrophytes (Kd, 1 X 10(-7) to 2 X 10(-7) M). Trichophyton rubrum had a protein with a higher binding affinity (Kd, 1.6 X 10(-8) M). Characterization of the [3H]progesterone-binding sites in T. mentagrophytes showed the binder to be a protein which was destroyed by trypsin and heating to 56 degrees C. Previous examination of the steroid-binding specificity in T. mentagrophytes had demonstrated that deoxycorticosterone (DOC) and dihydrotestosterone (DHT) were effective competitors for [3H]progesterone binding. Expansion of this study to include other competitors revealed that R5020 (a synthetic progestin), androstenedione, and dehydroepiandosterone possessed relative binding affinities which were 20, 11, and 9% of that of progesterone, respectively. Other ligands tested were less effective. Competition studies for the binder in M. canis resulted in similar findings: DOC and DHT were effective competitors for [3H]progesterone binding. The growth of A. benhamiae + and -, M. canis, and T. rubrum were all inhibited by progesterone in a dose-responsive manner, with 50% inhibition achieved at concentrations of 9.8 x 10(-6), 1.2 x 10(-5), 1.5 x 10(-5), and 2.7 x 10(-6) M. respectively,. PMID:3182998

  6. Increasing Progesterone Levels Are Associated With Smoking Abstinence Among Free-Cycling Women Smokers Who Receive Brief Pharmacotherapy

    PubMed Central

    McClure, Erin A.; Baker, Nathaniel L.; Carpenter, Matthew J.; Ramakrishnan, Viswanathan; Hartwell, Karen J.; Gray, Kevin M.

    2015-01-01

    Introduction: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. Methods: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. Results: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch–treated versus VAR-treated females. Conclusions: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed. PMID:25762749

  7. Effect of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) and Wistar (WF/NCr) rats.

    PubMed

    Shiraishi, N; Barter, R A; Uno, H; Waalkes, M P

    1994-09-01

    A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mumole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr) and then given cadmium (20 mumole CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing 53% mortality. Progesterone pretreatment had no effect on cadmium-induced lethality in WF rats or on testicular lesions in either strain. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated F344 rats given cadmium as compared to rats given Cd alone. Progesterone did not induce increases in hepatic or renal metallothionein (MT) and hepatic or testicular MT-I mRNA levels in F344 rats. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated F344 rats were doubled. This increase in TCBP provided no protection against cadmium toxicity in the testes. These results indicate that, in contrast to previously reported data for mice, progesterone pretreatment increased the lethality of cadmium in male F344 rats and had no effect on cadmium-induced testicular toxicity in F344 and WF rats. PMID:7843114

  8. Pregnancy rate in dairy cows treated with progesterone for six days during estrus synchronization with PGF2α.

    PubMed

    Orozco, M; Gutiérrez, C G; López, R; Aguilar, C; Roque, C; Hernández-Cerón, J

    2016-03-01

    The present study evaluated the effect of progesterone supplementation during a double PGF2α injection synchronization protocol on pregnancy per artificial insemination (P/AI) and on the incidence of twin births. Seven hundred and eighty three dairy cows were synchronized with two injections of PGF2α 14 days apart, starting on day 35 postpartum for their first postpartum insemination. Six days before the second PGF2α injection, cows were treated either with a progesterone-releasing intravaginal device (PRID-Delta) and an intramuscular injection of 500mg of progesterone (n=387) or served as control (n=396) and did not receive progesterone treatment. Cows were inseminated 12h after being detected in estrus. Pregnancy was diagnosed 40-45 days later by transrectal palpation. Progesterone administration improved (P<0.05) the percentage of cows detected in estrus in multiparous [(192/255) 75% vs (161/267) 60%], but not in primiparous cows [93/132 (70%) vs 90/129 (70%)]. Progesterone treatment increased P/AI in multiparous [53/192 (28%) vs 27/161 (17%)] but not in primiparous cows [25/93 (27%) vs 29/90 (32%)]. The incidence of twin births tended to be lower (P=0.09) in cows treated with progesterone [1/74 (1%)] than in the control group [4/53 (7%)]. It is concluded that progesterone administration during estrus synchronization with two PGF2α injections in dairy cows improves estral response and increases P/AI in multiparous, but not in primiparous cows, and tended to decrease the incidence of twin births.

  9. Divergent behavior of cyclin E and its low molecular weight isoforms to progesterone-induced growth inhibition in MCF-7 cells

    PubMed Central

    Montazeri, Hamed; Bouzari, Saeid; Azadmanesh, Kayhan; Ostad, Seyed Nasser; Ghahremani, Mohammad Hossein

    2015-01-01

    Background: Progesterone is a steroid hormone that modulates proliferation and differentiation in a cell phase and tissue-specific manner. Its function in breast cancer cells is of great significance since it can predict susceptibility of tumor cells to inhibitory effects of progesterone as adjuvant therapy. Materials and Methods: Stable clones overexpressing cyclin E (EL) and its low molecular weight isoforms (LMW-Es) were generated and treated with various concentrations of progesterone. Cell proliferation was assessed 24 and 48 h after the treatment. Changes in progesterone receptor (PR) expression were measured by real-time polymerase chain reaction. Results: Here we demonstrated that overexpression of EL and LMW-Es have divergent effects with regard to progesterone response. We found that progesterone could significantly decrease the growth rate of EL-expressing cells in the second cell cycle after treatment; however, progesterone was ineffective to arrest growth of LMW-Es expressing cells. PR expression level was at control level in EL-expressing cells but was downregulatedin LMW-Esexpressing clones. Conclusion: These results were in line with progesterone response of studied cells. The drop in PR expression together with altered distribution of p21 and p27 can explain different effects of cyclin E isoforms expression on progesterone responsivity. These data bring cyclin E status of cancer cells as a marker for predicting the efficacy of progesterone treatment. PMID:25625122

  10. Electron emission and product analysis of estrone: progesterone interactions studied by experiments in vitro

    PubMed Central

    GERSCHPACHER, MARION; GETOFF, NIKOLA; HARTMANN, JOHANNES; SCHITTL, HEIKE; DANIELOVA, IREN; YING, SHAOBIN; HUBER, JOHANNES C.; QUINT, RUTH M.

    2010-01-01

    Recent studies showed that hormones like progesterone, testosterone, etc. can eject eaq− (solvated electrons). By means of electron transfer processes via the brain, the hormones communicate with other biological systems in the organism. The present study proves that also estrone is able to emit electrons. Their yield strongly depends on the concentration of the hormone, temperature and on the absorbed energy. The metabolites resulting from this process are likewise able to generate electrons, however with much smaller yields. The formation of the estrone metabolites is studied by HPLC-analyses. In vitro experiments with MCF-7 cells demonstrate the distinct effect of progesterone on the carcinogenity of estrone metabolites. Probable reaction mechanisms for explanation of the observed effects are postulated. PMID:20586552

  11. [Prevention of preterm birth with vaginal progesterone in women with preterm labor: which are the evidences?].

    PubMed

    Martinez de Tejada, B; Othenin-Girard, V; Irion, O

    2015-10-28

    The presence of uterine contractions and a short cervix at less than 37 weeks of gestation (preterm labor) is an important risk factor for a preterm birth. Currently, there is not treatment able to reduce the risk of preterm birth in this high risk group of women. Vaginal progesterone has been shown to be effective in reducing the risk of preterm birth in asymptomatic women with a prior preterm birth and in women with a short cervix, measured by vaginal ultrasound before 24 weeks of gestation. Unfortunately, vaginal progesterone has not been shown to be efficacious in women with preterm labor. A recent clinical trial has shown that it can even be deleterious in this group of women.

  12. Serum progesterone concentrations associated with superovulation and premature corpus luteum failure in dairy goats.

    PubMed Central

    Stubbings, R B; Bosu, W T; Barker, C A; King, G J

    1986-01-01

    The incidence and cause of premature corpora lutea failure and the response to luteinizing hormone treatment was investigated in superovulated dairy goats. Does were treated with 1000 IU pregnant mare serum gonadotropin intramuscularly, followed by either luteinizing hormone (treated group) or saline (control group). Serum progesterone concentrations were used to monitor corpus luteum function. The dose of pregnant mare serum gonadotropin used induced superovulation in a majority of the does, but the responses varied depending on the time of year. Premature regression of the corpora lutea occurred in 4 of 18 does after pregnant mare serum gonadotropin treatment, but there was no difference in the incidence of corpora lutea failure between treated and control groups. Decreases in serum progesterone concentrations were evident by day 3 after ovulation in does that experienced corpora lutea failure indicating this to be the critical time for premature regression of the corpora lutea in superovulated does. PMID:3742374

  13. Serum progesterone concentrations associated with superovulation and premature corpus luteum failure in dairy goats.

    PubMed

    Stubbings, R B; Bosu, W T; Barker, C A; King, G J

    1986-07-01

    The incidence and cause of premature corpora lutea failure and the response to luteinizing hormone treatment was investigated in superovulated dairy goats. Does were treated with 1000 IU pregnant mare serum gonadotropin intramuscularly, followed by either luteinizing hormone (treated group) or saline (control group). Serum progesterone concentrations were used to monitor corpus luteum function. The dose of pregnant mare serum gonadotropin used induced superovulation in a majority of the does, but the responses varied depending on the time of year. Premature regression of the corpora lutea occurred in 4 of 18 does after pregnant mare serum gonadotropin treatment, but there was no difference in the incidence of corpora lutea failure between treated and control groups. Decreases in serum progesterone concentrations were evident by day 3 after ovulation in does that experienced corpora lutea failure indicating this to be the critical time for premature regression of the corpora lutea in superovulated does. PMID:3742374

  14. Water-soluble progesterone analogues are effective, injectable treatments in animal models of traumatic brain injury.

    PubMed

    Guthrie, David B; Stein, Donald G; Liotta, Dennis C; Lockwood, Mark A; Sayeed, Iqbal; Atif, Fahim; Arrendale, Richard F; Reddy, G Prabhakar; Evers, Taylor J; Marengo, Jose R; Howard, Randy B; Culver, Deborah G; Natchus, Michael G

    2012-05-10

    After more than 30 years of research and 30 failed clinical trials with as many different treatments, progesterone is the first agent to demonstrate robust clinical efficacy as a treatment for traumatic brain injuries. It is currently being investigated in two, independent phase III clinical trials in hospital settings; however, it presents a formidable solubility challenge that has so far prevented the identification of a formulation that would be suitable for emergency field response use or battlefield situations. Accordingly, we have designed and tested a novel series of water-soluble analogues that address this critical need. We report here the synthesis of C-20 oxime conjugates of progesterone as therapeutic agents for traumatic brain injuries with comparable efficacy in animal models of traumatic brain injury and improved solubility and pharmacokinetic profiles. Pharmacodynamic analysis reveals that a nonprogesterone steroidal analogue may be primarily responsible for the observed activity. PMID:24900479

  15. Analysis of estrogen and progesterone receptors on preoperative fine-needle aspirates.

    PubMed

    Frigo, B; Pilotti, S; Zurrida, S; Ermellino, L; Manzari, A; Rilke, F

    1995-01-01

    For 56 cases of carcinoma of the breast, results of the immunocytochemical assay for estrogen and progesterone receptors performed on preoperative fine-needle aspirates were compared with those obtained on scraping material from the same tumors. The value and usefulness of this last analysis was demonstrated in a previous study. The level of agreement between the two cytological techniques was assessed by the k statistic. A high level of agreement was found, with k values of 0.909 and 0.889 for estrogen and progesterone receptors, respectively. The results reported here revealed the reliability of steroid receptor determination on fine-needle aspiration biopsies, provided that sufficient cellularity was available. This technique can replace the open biopsy procedure, in as much as it represents a rapid, almost painless, and easily repeated method for the assessment of the receptor status, and is useful for treatment decisions at any time during the course of the disease.

  16. Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

    SciTech Connect

    Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

    1981-02-01

    The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations.

  17. Seasonal changes in serum progesterone levels in Thoroughbred racehorses in training

    PubMed Central

    TAKAHASHI, Yuji; AKAI, Makoto; MURASE, Harutaka; NAMBO, Yasuo

    2016-01-01

    ABSTRACT The objective of the present study was to verify the seasonal luteal activity of racehorses in training in Japan from March to August. We allocated 102 horses into a luteal activity group and non-luteal activity group. The luteal activity group included horses with serum progesterone levels that were consistently >1 ng/ml and changed by ± 1 ng/ml. In contrast, the progesterone levels of the non-luteal activity group were consistently <1 ng/ml. In late spring (from May 1 to June 30) and summer (from July 1 to August 31), the percentage of horses in the luteal activity group was significantly higher than in early spring (from March 1 to April 30, P<0.01). These findings demonstrate clear seasonal variations in ovarian activity. The present study also suggest that training for a race may not affect ovarian activity in female racehorses. PMID:26858579

  18. The Regulation of Embryo Implantation and Endometrial Decidualization by Progesterone Receptor Signaling

    PubMed Central

    Large, Michael J.; DeMayo, Francesco J.

    2011-01-01

    During the early stages of pregnancy, fertilized embryos must attach to the uterine epithelium, invade into the underlying uterine stroma, and the stroma must then differentiate in a process termed decidualization in order for a successful pregnancy to be initiated. The steroid hormone progesterone (P4) is an integral mediator of these early pregnancy events, exerting its effects via the progesterone receptor (PR). Insights gained from the use of mouse models and genomic profiling has identified many of the key molecules enlisted by PR to execute the paradigm of early pregnancy. This review describes several of the molecules through which the PR exerts its pleiotropic effects including ligands, receptors, chaperones, signaling proteins and transcription factors. Understanding these molecules and their concatenation is of vital importance to our ability to clinically treat reproductive health problems like infertility and endometriosis. PMID:21821095

  19. Meta-analysis of progesterone supplementation during timed artificial insemination programs in dairy cows.

    PubMed

    Bisinotto, R S; Lean, I J; Thatcher, W W; Santos, J E P

    2015-04-01

    A systematic review of the literature was performed with the objective to evaluate the effects of progesterone supplementation using a single intravaginal insert during timed artificial insemination (AI) programs on fertility in lactating dairy cows. A total of 25 randomized controlled studies including 8,285 supplemented cows and 8,398 untreated controls were included in the meta-analysis. Information regarding the presence of corpus luteum (CL) at the initiation of the synchronization protocol was available for 6,883 supplemented cows and 6,879 untreated controls in 21 experiments. Studies were classified based on service number (first AI vs. resynchronized AI), use of presynchronization (yes vs. no), and insemination of cows in estrus during the synchronization protocol (inseminated in estrus and timed AI vs. timed AI only). Reproductive outcomes of interest were pregnancy per AI (P/AI) measured on d 32 (27 to 42) and 60 (41 to 71) after AI, and pregnancy loss between d 32 and 60 of gestation. Random effects meta-analyses were conducted and treatment effect was summarized into a pooled risk ratio with the Knapp-Hartung modification (RRK+H). The effect of moderator variables was assessed using meta-regression analyses. Progesterone supplementation increased the risk of pregnancy on d 32 [RRK+H = 1.08; 95% confidence interval (CI) = 1.02-1.14] and 60 after AI (RRK+H = 1.10; 95% CI = 1.03-1.17). The benefit of progesterone supplementation was observed mainly in cows lacking a CL at the initiation of the timed AI program (d 60: RRK+H = 1.18; 95% CI = 1.07-1.30) rather than those with CL (d 60: RRK+H = 1.06; 95% CI = 0.99-1.12). Progesterone supplementation benefited P/AI in studies in which all cows were inseminated at timed AI (d 60: RRK+H = 1.20; 95% CI = 1.10-1.29), but not in studies in which cows could be inseminated in estrus during the timed AI program (d 60: RRK+H = 1.04; 95% CI = 0.92-1.16). Progesterone supplementation tended to reduce the risk of

  20. Plasma progesterone levels during oestrous cycle and their relationship with the ovulation rate in Red Sokoto (Maradi) goats.

    PubMed

    Pathiraja, N; Oyedipe, E O; Gyang, E O; Obasi, A

    1991-01-01

    Twenty-five 2-3-year-old cycling does weighing 17-25 kg were obtained from semi-nomadic farmers and managed under controlled conditions while simulating the traditional management system. Oestrus was synchronized using progestogen impregnated vaginal pessaries. Blood samples were collected daily for progesterone assay from the day of pessary withdrawal up to one complete oestrous cycle. Oestrus was checked twice daily using vasectomized bucks. Ovulation rate was determined by direct observation of the ovaries following laparotomy on day 5-7 of the oestrous cycle. Following oestrus synchronization, mean ovulation rate was 1.68 +/- 0.13. Mean oestrous cycle length and duration of oestrus were 21.30 +/- 0.28 days and 21.37 +/- 0.24 hours respectively. Plasma progesterone concentrations ranged from non-detectable levels on the day of oestrus to 5.2 +/- 0.28 ng ml at mid-cycle. The duration of elevated progesterone level (greater than 2 ng/ml) was about 12 days. The peak progesterone values did not differ between animals with different ovulation rates. However, the plasma progesterone concentration during the early cycle (days 0-6) was significantly lower in the single ovulators compared with others. There were no major differences in plasma progesterone levels during the oestrous cycle of Red Sokoto does with different ovulation rates. PMID:2018918

  1. Correlation of brain levels of progesterone and dehydroepiandrosterone with neurological recovery after traumatic brain injury in female mice.

    PubMed

    Lopez-Rodriguez, Ana Belen; Acaz-Fonseca, Estefania; Giatti, Silvia; Caruso, Donatella; Viveros, Maria-Paz; Melcangi, Roberto C; Garcia-Segura, Luis M

    2015-06-01

    Traumatic brain injury (TBI) is an important cause of disability in humans. Neuroactive steroids, such as progesterone and dehydroepiandrosterone (DHEA), are neuroprotective in TBI models. However in order to design potential neuroprotective strategies based on neuroactive steroids it is important to determine whether its brain levels are altered by TBI. In this study we have used a weight-drop model of TBI in young adult female mice to determine the levels of neuroactive steroids in the brain and plasma at 24h, 72 h and 2 weeks after injury. We have also analyzed whether the levels of neuroactive steroids after TBI correlated with the neurological score of the animals. TBI caused neurological deficit detectable at 24 and 72 h, which recovered by 2 weeks after injury. Brain levels of progesterone, tetrahydroprogesterone (THP), isopregnanolone and 17β-estradiol were decreased 24h, 72 h and 2 weeks after TBI. DHEA and brain testosterone levels presented a transient decrease at 24h after lesion. Brain levels of progesterone and DHEA showed a positive correlation with neurological recovery. Plasma analyses showed that progesterone was decreased 72 h after lesion but, in contrast with brain progesterone, its levels did not correlate with neurological deficit. These findings indicate that TBI alters the levels of neuroactive steroids in the brain with independence of its plasma levels and suggest that the pharmacological increase in the brain of the levels of progesterone and DHEA may result in the improvement of neurological recovery after TBI.

  2. Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to PIBF-receptor in lymphocytes.

    PubMed

    de la Haba, Carlos; Palacio, José R; Palkovics, Tamas; Szekeres-Barthó, Júlia; Morros, Antoni; Martínez, Paz

    2014-01-01

    Receptor-ligand binding is an essential interaction for biological function. Oxidative stress can modify receptors and/or membrane lipid dynamics, thus altering cell physiological functions. The aim of this study is to analyze how oxidative stress may alter receptor-ligand binding and lipid domain distribution in the case of progesterone-induced blocking factor/progesterone-induced blocking factor-receptor. For membrane fluidity regionalization analysis of MEC-1 lymphocytes, two-photon microscopy was used in individual living cells. Lymphocytes were also double stained with AlexaFluor647/progesterone-induced blocking factor and Laurdan to evaluate -induced blocking factor/progesterone-induced blocking factor-receptor distribution in the different membrane domains, under oxidative stress. A new procedure has been developed which quantitatively analyzes the regionalization of a membrane receptor among the lipid domains of different fluidity in the plasma membrane. We have been able to establish a new tool which detects and evaluates lipid raft clustering from two-photon microscopy images of individual living cells. We show that binding of progesterone-induced blocking factor to progesterone-induced blocking factor-receptor causes a rigidification of plasma membrane which is related to an increase of lipid raft clustering. However, this clustering is inhibited under oxidative stress conditions. In conclusion, oxidative stress decreases membrane fluidity, impairs receptor-ligand binding and reduces lipid raft clustering.

  3. Comparison of Risk of Preterm Labor between Vaginal Progesterone and17-Alpha-Hydroxy-Progesterone Caproate in Women with Threatened Abortion: A Randomized Clinical Trial

    PubMed Central

    Beigi, Abootaleb; Esmailzadeh, Arezoo; Pirjani, Reyhane

    2016-01-01

    Background Threatened miscarriage is a common complication in pregnancy that leads to adverse pregnancy outcomes such as preterm labor. This study aimed to compare the vaginal progesterone (Cyclogest) versus 17-alpha-hydroxyprogesterone caproate (Proluton) on preventing preterm labor in pregnant women with threatened abortion at less than 34 weeks’ gestational age. Materials and Methods This balanced randomized, double-blind, single-center controlled clinical trial included 190 women with threatened abortion. They were then randomly allocated into Cyclogest (n=95) and 17-alpha-hydroxyprogesterone caproate (Proluton, n=95) groups. Interested outcome was preterm labor less than 34 weeks. The Pearson chi-square and Student’s t test were used to compare two groups. The data were analyzed by Stata software version 13. Results The risks of preterm labor less than 34 weeks in Proluton and Cyclogest groups were 8.6 and 6.52%, respectively. There was no significant difference for risk of preterm labor less than 34 weeks [relative ratio (RR): 1.31, 95% confidence interval (CI): 0.47- 3.66, P=0.59] between two groups. Conclusion Risk of preterm labor in the vaginal progesterone group and 17-alpha-hydroxyprogesterone caproate group in pregnant women with threatened abortion is the same (Registration Number: IRCT2014123120504N1). PMID:27441048

  4. Differential effects of progesterone and genital stimulation on sequential inhibition of estrous behavior and progesterone receptor expression in the rat brain.

    PubMed

    Gómez-Camarillo, Madaí A; Beyer, Carlos; Lucio, Rosa Angélica; García-Juárez, Marcos; González-Arenas, Aliesha; Camacho-Arroyo, Ignacio; Komisaruk, Barry R; González-Flores, Oscar

    2011-05-30

    The effect of genital stimulation, either by vaginocervical stimulation (VCS) using a calibrated vaginal probe combined with manual flank stimulation (FS), or by mounts performed by the male, on the hypothalamus and preoptic area concentration of the progesterone receptors A (PR-A) and B (PR-B) was assessed in ovariectomized (ovx) estrogen-primed rats. VCS/FS or stimulation provided by male mounts, even without intromission, significantly decreased PR-B concentration in the hypoythalamus. Down regulation of PR produced by genital stimulation was quantitatively similar to that elicited by progesterone (P) administration. Bilateral or unilateral transection of the pelvic or the pudendal nerves prevented down regulation elicited by VCS/FS. Repeated VCS/FS elicited lordosis behavior in most ovx estrogen primed rats, but the lordosis intensity was lower than that observed in response to P. P administered to ovx estrogen primed rats, induced sequential inhibition, i.e., failure to display estrous behavior in response to a second P injection (24h after the initial P injection). VCS/FS failed to elicit sequential inhibition, since rats responded with normal estrous behavior to the second injection of P. This suggests that down regulation by VCS, by contrast with P, failed to inhibit the subpopulation of PR involved in the facilitation of estrous behavior by P.

  5. The progesterone level, leukocyte count and disgust sensitivity across the menstrual cycle.

    PubMed

    Żelaźniewicz, Agnieszka; Borkowska, Barbara; Nowak, Judyta; Pawłowski, Bogusław

    2016-07-01

    According to the compensatory prophylaxis hypothesis, women in the luteal phase, characterized by a high progesterone level, which suppresses various mechanisms of immune response, should exhibit higher disgust sensitivity, compared to the follicular phase. In this study we test the hypothesis on the compensatory role of disgust sensitivity at the luteal phase of the menstrual cycle, when immune functions are expected to change due to a rise in progesterone level. Disgust sensitivity, progesterone level (P) and white blood cell count (WBC), a general marker of immunocompetence, were measured in 30 healthy women of reproductive age. Disgust sensitivity was evaluated with: 1) Disgust Scale Revised (DS-R) containing three subscales: Core Disgust, Animal Reminder and Contamination Disgust, 2) Pathogen Disgust and Moral Disgust domains of the Three-Domain Disgust Scale. Measurements were conducted twice - in menstruation (the lowest P) and in the mid-luteal phase (the highest P). The results were analyzed longitudinally and using cross-sectional comparisons. Progesterone level, WBC count, and the level of disgust sensitivity in Animal Domain were higher in the mid-luteal phase comparing to menstruation. The level of disgust sensitivity (DS-R score, Animal, Contamination, Pathogen Disgust) correlated only with P (not WBC) and only in the mid-luteal phase (not in menstruation) in between-subjects comparisons. On the base of these results, we hypothesize that the level of disgust sensitivity in the whole menstrual cycle of a woman is "adjusted" to the luteal phase with the highest P level i.e. when immunosuppression is the greatest.

  6. Testosterone and Progesterone, But Not Estradiol, Stimulate Muscle Protein Synthesis in Postmenopausal Women

    PubMed Central

    Smith, Gordon I.; Yoshino, Jun; Reeds, Dominic N.; Bradley, David; Burrows, Rachel E.; Heisey, Henry D.; Moseley, Anna C.

    2014-01-01

    Context: The effect of the female sex steroids, estradiol and progesterone, on muscle protein turnover is unclear. Therefore, it is unknown whether the changes in the hormonal milieu throughout the life span in women contribute to the changes in muscle protein turnover and muscle mass (eg, age associated muscle loss). Objective: The objective of this study was to provide a comprehensive evaluation of the effect of sex hormones on muscle protein synthesis and gene expression of growth-regulatory factors [ie, myogenic differentiation 1 (MYOD1), myostatin (MSTN), follistatin (FST), and forkhead box O3 (FOXO3)]. Subjects and Design: We measured the basal rate of muscle protein synthesis and the expression of muscle growth-regulatory genes in 12 premenopausal women and four groups of postmenopausal women (n = 24 total) who were studied before and after treatment with T, estradiol, or progesterone or no intervention (control group). All women were healthy, and pre- and postmenopausal women were carefully matched on body mass, body composition, and insulin sensitivity. Results: The muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%–90% greater (all P < .05) in postmenopausal than premenopausal women. In postmenopausal women, both T and progesterone treatment increased the muscle protein fractional synthesis rate by approximately 50% (both P < .01), whereas it was not affected by estradiol treatment and was unchanged in the control group. Progesterone treatment increased MYOD1 mRNA expression (P < .05) but had no effect on MSTN, FST, and FOXO3 mRNA expression. T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression. Conclusion: Muscle protein turnover is faster in older, postmenopausal women compared with younger, premenopausal women, but these age-related differences do not appear to be explained by the age- and menopause-related changes

  7. Tapered progesterone withdrawal promotes long-term recovery following brain trauma.

    PubMed

    Cutler, Sarah M; Vanlandingham, Jacob W; Stein, Donald G

    2006-08-01

    We previously demonstrated that after traumatic brain injury (TBI), acute progesterone withdrawal (AW) causes an increase in anxiety behaviors and cerebro-cellular inflammation compared to tapered progesterone withdrawal (TW). Our current study investigates the behavioral and cellular effects of AW two weeks after termination of treatments to determine the longer-term influence of withdrawal after injury. Adult, male Sprague-Dawley rats received either bilateral frontal cortex contusion (L) or sham (S) surgery. Rats were injected at 1 and 6 h post-injury, then every 24 h for six days. Vehicle (V)-treated rats were given 9 injections of 22.5% cyclodextrin, whereas AW rats received 9 injections of 16 mg/kg progesterone and TW rats received 7 injections of P at 16 mg/kg, followed by one at 8 mg/kg and one at 4 mg/kg. On day 8, sensory neglect and locomotor activity tests were initiated. Animals were killed 22 days post-TBI and the brains prepared for either molecular or histological analysis. Western blotting revealed increased brain-derived neurotrophic factor (BDNF) and heat shock protein 70 (HSP70) in TW vs. AW animals. P53 was increased in VL animals, whereas all progesterone-treated groups were equivalent to shams. TW animals had markedly decreased sensory neglect compared to AW animals and increased center time in locomotor activity assays. In addition, lesion reconstruction revealed a decreased lesion size for TWL over AWL over VL animals. Glial fibrillary acidic protein (GFAP) immunofluorescent staining followed this pattern as well. In conclusion, after TBI, AW affects select behaviors and molecular markers in the chronic recovery period. PMID:16797538

  8. Progesterone improves the maturation of male-induced preovulatory follicles in anoestrous ewes.

    PubMed

    Adib, Achraf; Freret, Sandrine; Touze, Jean-Luc; Lomet, Didier; Lardic, Lionel; Chesneau, Didier; Estienne, Anthony; Papillier, Pascal; Monniaux, Danielle; Pellicer-Rubio, Maria-Teresa

    2014-10-01

    The first ovulation induced by male effect in sheep during seasonal anoestrus usually results in the development of a short cycle that can be avoided by progesterone priming before ram introduction. In elucidating the involvement of the hypothalamic-pituitary-gonadal axis in the occurrence of short cycles, the effects of progesterone and the time of anoestrus on the development of male-induced preovulatory follicles were investigated in anoestrous ewes using morphological, endocrine and molecular approaches. Ewes were primed with progesterone for 2 (CIDR2) or 12 days (CIDR12) and untreated ewes used as controls during early (April) and late (June) anoestrus. The duration of follicular growth and the lifespan of the male-induced preovulatory follicles were prolonged by ∼1.6 days in CIDR12 ewes compared with the controls. These changes were accompanied by a delay in the preovulatory LH and FSH surges and ovulation. Intra-follicular oestradiol concentration and mRNA levels of LHCGR and STAR in the granulosa and theca cells of the preovulatory follicles were higher in CIDR12 ewes than the control ewes. The expression of mRNA levels of CYP11A1 and CYP17A1 also increased in theca cells of CIDR12 ewes. CIDR2 ewes gave intermediate results. Moreover, ewes ovulated earlier in June than in April, without changes in the duration of follicular growth, but these effects were unrelated to the lifespan of corpus luteum. Our results give the first evidence supporting the positive effect of progesterone priming on the completion of growth and maturation of preovulatory follicles induced by male effect in seasonal anoestrous ewes, thereby preventing short cycles.

  9. Behavioral effects of interleukin-1 beta: modulation by gender, estrus cycle, and progesterone.

    PubMed

    Avitsur, R; Donchin, O; Barak, O; Cohen, E; Yirmiya, R

    1995-09-01

    Endogenous release or exogenous administration of the cytokine Interleukin-1 (IL-1) produces several behavioral alterations, including suppression of locomotion and exploration. Because there are bidirectional interactions between IL-1 and the hypothalamic-pituitary-gonadal axis, we investigated possible differences between males and females in various phases of the estrus cycle in the behavioral effects of IL-1. In addition, we assessed the role of progesterone in mediating estrus cycle-dependent differences in these effects. Female rats in either the estrus or the non-estrus phase of their cycle and male rats were injected with either IL-1 beta (2 or 5 micrograms/kg) or saline. Activity in the open field test was measured 2 h later by counting the number of line crossings and rearings. In saline-injected rats, nonestrus females performed less line crossings than estrus females. IL-1 produced a significant dose-dependent reduction of line crossing in males and estrus females. In contrast, in nonestrus females the lower dose of IL-1 had no effect, and the effect of the higher dose was significantly smaller in nonestrus than in estrus females. The higher dose of IL-1 suppressed rearing in all three groups, but the effect of the lower dose on the number of rearings was significant only in estrus females. In a second experiment, ovariectomized females were injected with either progesterone (2 mg/rat) or oil, followed 2 h later by an injection of either IL-1 beta (2 micrograms/kg) or saline. Activity was measured continuously by a biotelemetric system. IL-1 reduced activity in progesterone-treated ovariectomized females but not in oil-injected controls. These findings suggest that changes in progesterone secretion along the estrus cycle modulate the behavioral responsiveness to IL-1 in female rats.

  10. Pituitary progesterone receptor expression and plasma gonadotrophin concentrations in the reproductively dysfunctional mutant restricted ovulator chicken.

    PubMed

    Ocón-Grove, Olga M; Maddineni, Sreenivasa; Hendricks, Gilbert L; Elkin, Robert G; Proudman, John A; Ramachandran, Ramesh

    2007-04-01

    Female mutant restricted ovulator (RO) chickens of the White Leghorn strain carry a naturally occurring single nucleotide mutation in the very low density lipoprotein receptor (VLDLR) gene. Due to this mutation, RO hens fail to express a functional VLDLR protein on the oocyte membrane, which results in an impaired uptake of circulating yolk precursor macromolecules. Mutant RO hens subsequently develop hyperlipidemia and generally fail to lay eggs due to follicular atresia. Since RO hens also reportedly have three-fold higher basal plasma estrogen concentrations, combined with four-fold lower levels of circulating progesterone as compared to wild-type (WT) hens, we hypothesized that RO hens would have an increased abundance of pituitary progesterone receptor (PR) mRNA and PR isoforms A and B as well as alterations in circulating gonadotrophin levels. Quantitative PCR assays revealed significantly greater (Pprogesterone levels. Collectively, elevated circulating estrogen and/or decreased progesterone levels may have contributed to the upregulation of PR mRNA and PR isoforms A and B in the RO hen pituitary gland. Lastly, in order to gain a more complete understanding of why RO hens are reproductively dysfunctional, a model is proposed that links humoral and ovarian factors to observed and putative changes in the hypothalamic-pituitary axis.

  11. Monitoring the gestation period of rescued Formosan pangolin (Manis pentadactyla pentadactyla) with progesterone radioimmunoassay.

    PubMed

    Chin, Shih-Chien; Lien, Chen-Yen; Chan, Ya-Ting; Chen, Chun-Lin; Yang, Yi-Ching; Yeh, Lih-Seng

    2012-01-01

    Eight species of pangolin have been identified in the world. However, understanding of pangolin reproductive biology has been limited to fragmentary records. In this study, the concentration of serum progesterone in three pregnant and two nonpregnant rescued female Formosan pangolins (Manis pentadactyla pentadactyla) was monitored using a commercial progesterone radioimmunoassay kit. During gestation, the serum progesterone of pregnant pangolins A, B, and C remained at 28.5-55 ng/ml (n = 31 samples), 10.9-50.1 ng/ml (n = 34), and 12.4 and 33.5 ng/ml with a peak at 47.6 ng/ml (n = 19), respectively, whereas the serum progesterone of nonpregnant pangolins D and E remained at 1.99 ± 1.62 ng/ml (n = 80) and 2.27 ± 1.64 ng/ml (n = 27), respectively. From this study, it was found that female pangolin weighing as low as 2.14 kg was already capable of reproduction. For pregnant pangolins to give birth to viable offspring, their body weight must increase significantly, 63.89 and 134.0% in the study, from the time of inception or early pregnancy until parturition. In addition, study has found that both viable offspring were born fully developed and exceeded 80 g in weight. The period of gestation was found to be as short as 318 or longer than 372 days. Therefore, the Formosan pangolin should only be able to reproduce once a year. This study is the first insight into hormone assay for determining the gestation period of pangolin. Further investigations on the same subject are necessary to establish criteria for the recognition of reproductive status in pangolins. PMID:21866570

  12. Progesterone sperm chemoattraction may be modulated by its corticosteroid-binding globulin carrier protein.

    PubMed

    Teves, Maria Eugenia; Guidobaldi, Hector Alejandro; Uñates, Diego Rafael; Sanchez, Raul; Miska, Werner; Giojalas, Laura Cecilia

    2010-05-01

    Progesterone, the main steroidal component secreted by the cumulus cells that surround the egg, chemotactically guides human spermatozoa. The aim of this work was to evaluate whether the carrier protein corticosteroid-binding globulin also participates in the sperm P chemotactic response. By means of videomicroscopy and image analysis, we observed that corticosteroid-binding globulin modulates the chemotactic activity of P, when a solution of corticosteroid-binding globulin + P is at the nanomolar range.

  13. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Bhat, G. K.; Yang, H.; Sridaran, R.

    2001-01-01

    The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.

  14. A Truncated Progesterone Receptor (PR-M) Localizes to the Mitochondrion and Controls Cellular Respiration

    PubMed Central

    Dai, Qunsheng; Shah, Anish A.; Garde, Rachana V.; Yonish, Bryan A.; Zhang, Li; Medvitz, Neil A.; Miller, Sara E.; Hansen, Elizabeth L.; Dunn, Carrie N.

    2013-01-01

    The cDNA for a novel truncated progesterone receptor (PR-M) was previously cloned from human adipose and aortic cDNA libraries. The predicted protein sequence contains 16 unique N-terminal amino acids, encoded by a sequence in the distal third intron of the progesterone receptor PR gene, followed by the same amino acid sequence encoded by exons 4 through 8 of the nuclear PR. Thus, PR-M lacks the N terminus A/B domains and the C domain for DNA binding, whereas containing the hinge and hormone-binding domains. In this report, we have localized PR-M to mitochondria using immunofluorescent localization of a PR-M-green fluorescent protein (GFP) fusion protein and in Western blot analyses of purified human heart mitochondrial protein. Removal of the putative N-terminal mitochondrial localization signal obviated association of PR-M with mitochondria, whereas addition of the mitochondrial localization signal to green fluorescent protein resulted in mitochondrial localization. Immunoelectron microscopy and Western blot analysis after mitochondrial fractionation identified PR-M in the outer mitochondrial membrane. Antibody specificity was shown by mass spectrometry identification of a PR peptide in a mitochondrial membrane protein isolation. Cell models of overexpression and gene silencing of PR-M demonstrated a progestin-induced increase in mitochondrial membrane potential and an increase in oxygen consumption consistent with an increase in cellular respiration. This is the first example of a truncated steroid receptor, lacking a DNA-binding domain that localizes to the mitochondrion and initiates direct non-nuclear progesterone action. We hypothesize that progesterone may directly affect cellular energy production to meet the increased metabolic demands of pregnancy. PMID:23518922

  15. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    PubMed Central

    Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

    2013-01-01

    The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl-, respectively) and renal and plasma catecholamine release concentrations. FENa+, FECl-, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+, FECl-, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function. PMID:23828583

  16. Monitoring the gestation period of rescued Formosan pangolin (Manis pentadactyla pentadactyla) with progesterone radioimmunoassay.

    PubMed

    Chin, Shih-Chien; Lien, Chen-Yen; Chan, Ya-Ting; Chen, Chun-Lin; Yang, Yi-Ching; Yeh, Lih-Seng

    2012-01-01

    Eight species of pangolin have been identified in the world. However, understanding of pangolin reproductive biology has been limited to fragmentary records. In this study, the concentration of serum progesterone in three pregnant and two nonpregnant rescued female Formosan pangolins (Manis pentadactyla pentadactyla) was monitored using a commercial progesterone radioimmunoassay kit. During gestation, the serum progesterone of pregnant pangolins A, B, and C remained at 28.5-55 ng/ml (n = 31 samples), 10.9-50.1 ng/ml (n = 34), and 12.4 and 33.5 ng/ml with a peak at 47.6 ng/ml (n = 19), respectively, whereas the serum progesterone of nonpregnant pangolins D and E remained at 1.99 ± 1.62 ng/ml (n = 80) and 2.27 ± 1.64 ng/ml (n = 27), respectively. From this study, it was found that female pangolin weighing as low as 2.14 kg was already capable of reproduction. For pregnant pangolins to give birth to viable offspring, their body weight must increase significantly, 63.89 and 134.0% in the study, from the time of inception or early pregnancy until parturition. In addition, study has found that both viable offspring were born fully developed and exceeded 80 g in weight. The period of gestation was found to be as short as 318 or longer than 372 days. Therefore, the Formosan pangolin should only be able to reproduce once a year. This study is the first insight into hormone assay for determining the gestation period of pangolin. Further investigations on the same subject are necessary to establish criteria for the recognition of reproductive status in pangolins.

  17. Occlusive and Non-Occlusive Application of Microemulsion for Transdermal Delivery of Progesterone: Mechanistic Studies

    PubMed Central

    El Maghraby, Gamal M.

    2012-01-01

    This work evaluated the occlusive versus non-occlusive application of microemulsion (ME) for the transdermal delivery of progesterone. The mechanisms of enhanced skin penetration were investigated. ME comprised of oleic acid, Tween 80, propylene glycol, and water, was used neat or with ethanol as a volatile cosurfactant. The ME formulations enhanced progesterone transdermal flux compared to the saturated drug solution in 14% aqueous propylene glycol (control). Ethanol-containing ME (EME) was better than the ethanol-free system (EFME). Open application of EFME produced a marginal reduction in flux compared to occlusive application. For EME, open application reduced the flux by 26–28% with the flux remaining significantly higher than that obtained with EFME. The mechanistic studies revealed synergism between ethanol and EFME with EME, producing greater flux than the sum of fluxes obtained from 40% ethanol in water and EFME. Penetration enhancement and supersaturation played a role in enhanced transdermal delivery, but other mechanisms were also possible. This study thus introduced EME as a transdermal delivery system for progesterone with good potential for open application as a spray. PMID:23008820

  18. Finasteride inhibits the disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis.

    PubMed

    Samba Reddy, Doodipala; Ramanathan, G

    2012-09-01

    Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively susceptible to recurrent, unprovoked seizures due to precipitating risk factors. Progesterone has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. Progesterone markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of the limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy.

  19. Pregnancy diagnosis in dairy goats using progesterone assay kits and oestrous observation.

    PubMed

    Engeland, I V; Ropstad, E; Andresen, O; Eik, L O

    1997-06-01

    Two qualitative on-farm milk progesterone test kits were used for early pregnancy diagnosis in goats. One kit was based on latex agglutination (LA) and the other on enzyme-linked immunosorbent assay (ELISA). The accuracy of early pregnancy diagnosis by these two methods was compared with the accuracy of oestrous observation (OeO) and the level of plasma progesterone measured by radioimmunoassay (RIA). Dairy goats (n = 73) from a single herd were used for collection of milk and blood samples 20 days after breeding. Ultrasound examination 50 days after mating found that 49 (67%) goats were pregnant, and 24 (33%) were not pregnant. Using ultrasound as a reference method, the accuracy of early pregnancy diagnosis by RIA and OeO was 92% and 86%, respectively, and for non-pregnancy 100% for both RIA and OeO. The accuracy of early pregnancy diagnosis by ELISA and LA was 82% and 79% and for non-pregnancy, 88% and 100%, respectively. The kappa-statistic for RIA, OeO, ELISA and LA was 0.93, 0.84, 0.77 and 0.73, respectively. It was concluded that LA and ELISA tests can be used for early pregnancy diagnosis in dairy goats. However, in the herd studied, early pregnancy diagnosis by OeO was as good as that achieved with progesterone determination using the kits. PMID:9329865

  20. Enhanced sexual behaviors and androgen receptor immunoreactivity in the male progesterone receptor knockout mouse.

    PubMed

    Schneider, Johanna S; Burgess, Carly; Sleiter, Nicole C; DonCarlos, Lydia L; Lydon, John P; O'Malley, Bert; Levine, Jon E

    2005-10-01

    Reproductive and behavioral functions of progesterone receptors (PRs) in males were assessed by examining consequences of PR gene deletion. Basal hormone levels were measured in male progesterone receptor knockout (PRKO) mice and compared to wild-type (WT) counterparts. RIA of serum LH, testosterone, and progesterone levels revealed no significant differences. Levels of FSH were moderately but significantly lower and inhibin levels were higher in PRKOs; these differences were not accompanied by gross differences in testicular weight or morphology. PRKOs exhibited significant alterations in sexual behavior. In initial tests PRKOs exhibited reduced latency to mount, compared with WT. In second sessions, PRKOs again showed a significantly reduced latency to mount and increased likelihood of achieving ejaculation. RU486 treatment in WT produced increased mount and intromission frequency and decreased latency to intromission. In anxiety-related behavior tests, PRKO mice exhibited intermediate anxiety levels, compared with WT, suggesting that enhanced sexual behavior in PRKOs is not secondary to reduced anxiety. Immunohistochemical analysis revealed significantly enhanced androgen receptor expression in the medial preoptic nucleus and bed nucleus of the stria terminalis of PRKO. We conclude that testicular development and function and homeostatic regulation of the hypothalamic-pituitary testicular axis are altered to a lesser extent by PR gene deletion. In contrast, PR appears to play a substantial role in inhibiting the anticipatory/motivational components of male sexual behavior in the mouse. The biological significance of this inhibitory mechanism and the extent to which it is mediated by reduced androgen receptor expression remain to be clarified.

  1. Progesterone regulation of AVEN protects bovine oocytes from apoptosis during meiotic maturation.

    PubMed

    O'Shea, Lynne C; Hensey, Carmel; Fair, Trudee

    2013-12-01

    Inhibition of progesterone (P4) synthesis by cumulus cells during bovine in vitro oocyte maturation (IVM) causes a decrease in subsequent embryo development, indicating that P4 intracellular signaling within the cumulus oocyte complex (COC) is important for oocyte developmental competence. The aim of the present study was to further elucidate, on a protein level, the downstream signaling pathway involved in P4 regulation of oocyte developmental competence. COCs were subjected to IVM for 24 h in the presence or absence of trilostane, aglepristone, or promegestone (R5020). These altered IVM conditions resulted in dynamic changes in protein expression of the progesterone receptors and the cell death-regulated proteins AVEN, BCL-xL, and active caspase 3. In addition, AVEN protein localization, caspase 3 activation, and mitochondrial distribution were studied by immunofluorescence. Inhibition of progesterone synthesis (trilostane treatment) resulted in changes in AVEN localization within the COC, corresponding to caspase 3 activation and altered mitochondrial distribution. AVEN was also found to bind BCL-xL in COCs, but this interaction was lost following treatment with trilostane.

  2. Progesterone receptors in normal mammary gland: receptor modulations in relation to differentiation

    PubMed Central

    1980-01-01

    The biological basis for the observed modulation in cytoplasmic progesterone receptors (PgR) of normal mammary gland occurring during mammary development was investigated. Specifically, the relative roles of hormones vs. differentiation on (a) the decrease in PgR concentration during pregnancy and lactation and (b) the loss of mammary responsiveness to estrogen during lactation were examined. PgR were measured using the synthetic progestin, R5020, as the ligand. The hormones estrogen and progesterone were tested in vivo for their effect of PgR concentration. Mammary gland differentiation was assessed morphologically and by measuring enzymatically active alpha- lactalbumin. These studies show that there is a stepwise decrease in PgR that occurs in two stages. The first decrease is completed by day 12 of pregnancy and the second decrease occurs only after parturition. There appears to be a hormonal basis for the first decrease and it appears to be caused by the negative effect of progesterone on estrogen- mediated increase in PgR. In direct contrast, the absence of PgR during lactation and the mammary tissue insensitivity to estrogenic stimulation of PgR were not related to the hormonal milieu of lactation but were directly related to the secretory state of the mammary gland and lactation per se. PMID:7410476

  3. Form and function: how estrogen and progesterone regulate the mammary epithelial hierarchy.

    PubMed

    Arendt, Lisa M; Kuperwasser, Charlotte

    2015-06-01

    The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation, the alveoli undergo apoptosis, and the mammary gland reverses back to resemble the nonparous gland. This process of growth and regression occurs for multiple pregnancies, suggesting the presence of a hierarchy of stem and progenitor cells that are able to regenerate specialized populations of mammary epithelial cells. Expansion of epithelial cell populations in the mammary gland is regulated by ovarian steroids, in particular estrogen acting through its receptor estrogen receptor alpha (ERα) and progesterone signaling through progesterone receptor (PR). A diverse number of stem and progenitor cells have been identified based on expression of cell surface markers and functional assays. Here we review the current understanding of how estrogen and progesterone act together and separately to regulate stem and progenitor cells within the human and mouse mammary tissues. Better understanding of the hierarchal organization of epithelial cell populations in the mammary gland and how the hormonal milieu affects its regulation may provide important insights into the origins of different subtypes of breast cancer.

  4. Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone.

    PubMed

    Armanini, Decio; Bordin, Luciana; Donà, Gabriella; Sabbadin, Chiara; Bakdounes, Leila; Ragazzi, Eugenio; Giorgino, Francesco L; Fiore, Cristina

    2012-05-01

    A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk. PMID:22387621

  5. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  6. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  7. Progesterone--specific binding sites in the kidney of the female baboon

    SciTech Connect

    Weaker, F.J.; Herbert, D.C.; Sheridan, P.J.

    1984-10-01

    The uptake and retention of a radiolabeled synthetic progestin, ORG 2058, was studied in the urinary tract of the female baboon. Four estrogen-primed baboons were injected intravenously with 2.5 micrograms./kg. body weight of 3H-ORG 2058. One animal, which served as a control, received an additional injection of 2.5 mg./kg. body weight of unlabeled progesterone. One hour after the injections, the animals were killed and the kidneys, ureters and urinary bladder were removed and processed for autoradiography. Localization of progestin was observed in the nuclei of the convoluted and straight segments of the distal tubule, the ascending thick limb of the loop of Henle and both cortical and medullary collecting tubules. Connective tissue cells were also labeled in the medulla and cortex of the kidney. An absence of silver grains was noted in the renal corpuscle, all segments of the proximal tubule and the thin loop of Henle. Concentration of the tritiated steroid was not observed in either the ureter or bladder or in any portions of the urinary tract of the control animal. This study suggests that progesterone has a direct effect via a progesterone specific receptor on the various target cells that sequestered the 3H-ORG 2058.

  8. Comparison of different progestagen assays for measuring progesterone metabolites in faeces of the bitch.

    PubMed

    Möstl, E; Brunner, I

    1997-12-01

    From 12 bitches of various breeds with fertile oestrus cycles faecal samples were collected daily from the onset of pro-oestrus till 20 days after the start of vulval bleeding, then once per week till about 1 week before term. Immunoreactive progesterone metabolites were extracted from the samples using methanol and measured using immunoassays. In a first experiment four different assays were compared in regard to the amounts of immunoreactive substances measured: the enzyme immunoassay against 20-oxo-3-hydroxypregnanes showed twice to four times higher values of immunoreactive material than another using an antibody against 6 beta-hydroxyprogesterone. An enzyme immunoassay for pregnanediol measured only low concentrations of immunoreactive material. Also a radio immunoassay using an antibody against 11 beta-hydroxyprogesterone detected only small amounts of reacting material. High performance liquid chromatography showed that in faeces of bitches the immunoreactive progesterone metabolites were present in unconjugated form, mainly as 3 alpha/beta hydroxylated progestagens with a 20-oxo group. In the second experiment the samples were measured with the assay system using the 20-oxo-3-hydroxypregnane antibody. A few days before mating the concentration of progesterone metabolites increased, reaching 5.77 mumol/kg faeces (median) at the day of mating. High levels (10.45 mumol/kg faeces) were measured till the end of the first month after mating. Thereafter, the concentrations decreased, reaching 2.68 mumol/kg (median) at the end of the second month.

  9. Acculturation, depressive symptoms, estriol, progesterone, and preterm birth in Hispanic women

    PubMed Central

    Marti, C. Nathan; Pickler, Rita; Murphey, Christina; Wommack, Joel; Brown, Charles E. L.

    2012-01-01

    We examined the effects of acculturation, depressive symptoms, progesterone, and estriol (E3) as predictors of preterm birth (PTB) in pregnant Hispanic women. This cross-sectional study recruited a sample of 470 Hispanic women between 22- and 24-week gestation from physician practices and community clinics. We used the CES-D to measure maternal depressive symptoms. We measured acculturation by English proficiency on the Bidimensional Acculturation Scale, residence index by years in the USA minus age, nativity, and generational status. Serum progesterone and E3 were analyzed by EIA. Ultrasound and medical records determined gestational age after delivery. In χ2 analysis, there were a significantly greater percentage of women with higher depressive scores if they were born in the USA. In a structural equation model (SEM), acculturation (English proficiency, residence index, and generational status) predicted the estriol/progesterone ratio (E/P), and the interaction of depressive symptoms with the E/P ratio predicted PTB. Undiagnosed depressive symptoms during pregnancy may have biological consequences increasing the risk for PTB. PMID:22277971

  10. Progesterone supplementation during multiple ovulation treatment in buffalo species (Bubalus bubalis).

    PubMed

    Neglia, Gianluca; Gasparrini, Bianca; Vecchio, Domenico; Rubessa, Marcello; Di Palo, Rossella; Zicarelli, Luigi; Campanile, Giuseppe

    2010-08-01

    The aim of this study was to evaluate the effect of exogenous progesterone supplementation on superovulatory response in buffaloes that has undergone a multiple ovulation program. Fourteen Mediterranean buffaloes were divided into two groups and received a 4-day decreasing dosage of an equal mixture of 500 IU of FSH and LH starting on day 8 of the cycle. In group A (n = 7) a progesterone-releasing intravaginal device was removed on day 8, whereas in group B (n = 7) it was left till day 10, when PGF2alpha was administered. Eighty hours later, buffaloes were artificially inseminated and after 6 days they undergone uterine flushing. A higher (P < 0.05) number of corpora lutea (8.3 vs. 5.7) and embryo/flushing/buffalo (2.3 vs. 1.3) were recorded in group B vs. group A if responsive buffaloes are considered (n = 12) and the number of corpora lutea was highly correlated with the number of embryos (r = 0.65; P < 0.05). In conclusion, progesterone supplementation during the first 2 days of the superovulation treatment seems to enhance the recovery rate in buffalo species. A high ovulation rate, associated with a high number of corpora lutea, can represent a parameter for estimating embryo recovery. PMID:20411328

  11. The progesterone and estrogen modify the uterine prolactin and prolactin receptor expression of hyperprolactinemic mice.

    PubMed

    do Amaral, Vinícius Cestari; Carvalho, Kátia Candido; Maciel, Gustavo Arantes Rosa; Simoncini, Tommaso; da Silva, Priscilla Ludovico; Marcondes, Rodrigo Rodrigues; Soares, José Maria; Baracat, Edmund Chada

    2015-02-01

    The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and PRL receptor's expression in the uterus of mice. For this purpose, 49 Swiss mice were divided into the following groups: GrSS (non-ovariectomized mice given vehicle); GrMET (non-ovariectomized mice treated with metoclopramide); OvSS (ovariectomized mice given vehicle); OvMET (ovariectomized mice treated with metoclopramide); OvMET+17βE (ovariectomized mice treated with metoclopramide and 17β estradiol); OvMET+MP (ovariectomized mice treated with metoclopramide and micronized progesterone); OvMET+17βE+MP (ovariectomized mice treated with metoclopramide and a solution of 17β estradiol and micronized progesterone). Immunohistochemical analyzes were evaluated semi-quantitatively. Our results showed that GrMET, OvMET+MP, and OvMET+17βE+MP presented strong PRL expression. OvMET and OvMET+17βE presented mild reaction, while GrSS and OvSS presented weak reaction. Concerning PRL receptor, OvMET+MP and OvMET+17βE+MP showed strong reaction; GrMET, OvSS, and OvMET+17βE showed mild reaction; and GrSS and OvMET showed weak reaction. These findings suggest that progesterone alone or in combination with estrogen may increase the expression of uterine PRL and PRL receptor.

  12. Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method.

    PubMed

    Araya-Sibaja, Andrea Mariela; Soldi, Valdir; Campos, Carlos Eduardo Maduro; Cardoso, Simone Gonçalves; Cuffini, Silvia Lucia

    2015-05-01

    Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications. PMID:24758712

  13. Progesterone prevents linkage of rabbit myometrial alpha 2-adrenergic receptors to inhibition of adenylate cyclase.

    PubMed

    Wu, Y Y; Riemer, R K; Goldfien, A; Roberts, J M

    1989-04-01

    The uterine response to adrenergic stimulation is determined by the hormonal milieu. This response is particularly well characterized in the rabbit. In this species, as in humans, the response of the uterus to sympathetic stimulation is alpha-adrenergically mediated contraction with elevated circulating estrogen. However, with progesterone predominance, similar stimulation inhibits uterine contractions, a response mediated by beta-adrenergic receptors acting through their second message, cyclic adenosine monophosphate. We studied the mechanisms by which sex steroids regulate myometrial adrenergic responses. In this study, we questioned whether part of the effect of sex steroids could be explained by an alteration of the coupling of the alpha 2-adrenergic receptor to the inhibition of adenylate cyclase. We found that in the progesterone-treated rabbit, although alpha 2-receptors are present, they are not linked to inhibition of cyclic adenosine monophosphate synthesis. The net synthesis of cyclic adenosine monophosphage in response to endogenous catecholamines is determined by their activation of beta-adrenergic receptors to increase and alpha 2-receptors to decrease cyclic adenosine monophosphate formation. Thus the uncoupling of alpha 2-receptors contributes to increased intracellular cyclic adenosine monophosphate in myometrium of progesterone-treated animals consistent with the reported predominance of beta-adrenergic contractile responses in this setting.

  14. Acculturation, depressive symptoms, estriol, progesterone, and preterm birth in Hispanic women.

    PubMed

    Ruiz, R Jeanne; Marti, C Nathan; Pickler, Rita; Murphey, Christina; Wommack, Joel; Brown, Charles E L

    2012-02-01

    We examined the effects of acculturation, depressive symptoms, progesterone, and estriol (E3) as predictors of preterm birth (PTB) in pregnant Hispanic women. This cross-sectional study recruited a sample of 470 Hispanic women between 22- and 24-week gestation from physician practices and community clinics. We used the CES-D to measure maternal depressive symptoms. We measured acculturation by English proficiency on the Bidimensional Acculturation Scale, residence index by years in the USA minus age, nativity, and generational status. Serum progesterone and E3 were analyzed by EIA. Ultrasound and medical records determined gestational age after delivery. In χ (2) analysis, there were a significantly greater percentage of women with higher depressive scores if they were born in the USA. In a structural equation model (SEM), acculturation (English proficiency, residence index, and generational status) predicted the estriol/progesterone ratio (E/P), and the interaction of depressive symptoms with the E/P ratio predicted PTB. Undiagnosed depressive symptoms during pregnancy may have biological consequences increasing the risk for PTB. PMID:22277971

  15. Identification of testosterone and progesterone in hemolymph of larvae of the fleshfly Sarcophaga bullata.

    PubMed

    De Clerck, D; Eechaute, W; Leusen, I; Diederik, H; De Loof, A

    1983-12-01

    Testosterone- and progesterone-like substances were detected by radioimmunoassay (RIA) in chromatographed extracts of hemolymph from larvae of Sarcophaga bullata (S.B.). Gas chromatographic (GC) analysis after heptafluorobutyric acid (HFBA) derivation of hemolymph extracts, purified by paper and silica gel column chromatography, showed a peak in the GC recordings with the same retention time as the HFBA derivative of pure testosterone. A testosterone concentration of 92 ng/100 ml hemolymph was found by GC; the concentration of progesterone, calculated on the basis of the RIA, was about two times higher. After preparing the o-pentafluorobenzyloxime (OPFB)-heptafluorobutyryl ester (HFB) derivatives of the hemolymph extracts, negative ion chemical ionization capillary gas chromatography-mass spectrometry (NCI/GC-MS) proved that hemolymph of larvae of the fleshfly Sarcophaga bullata indeed contains testosterone and progesterone. Several metabolites and precursors of the latter compounds could also be detected during the NCI/GC-MS analyses. Estrogens could not be traced by any of the methods we used. This is the first time that these steroids have been identified in insect hemolymph. These results add interesting perspectives for comparative endocrinology.

  16. Peripartal changes of estrone, progesterone and prostaglandin in the water buffalo.

    PubMed

    Perera, B M; Abeygunawardena, H; Thamotharam, A; Kindahl, H; Edqvist, L E

    1981-05-01

    The peripheral blood plasma concentration of estrone, progesterone and 15-keto-13, 14-dihydroprostaglandin F2alpha (PGF2alpha metabolite) were determined by radioimmunoassay techniques during the peripartal period in 5 buffalo cows belonging to a river type breed. Estrone levels started to increase from below 200 pg/ml about 15 days prior to parturition, and reached high concentrations (400-750 pg/ml) during the last 5 days of pregnancy. The estrone concentration decreased to baseline levels after delivery. The concentration of progesterone fluctuated between 800 and 2000 pg/ml until 15 days before calving and showed a gradual increase during the last 15 days of pregnancy. The progesterone levels declined abruptly on the day of calving and remained below 100 pg/ml for up to 60 days post-partum. Increased levels of the prostaglandin metabolite were recorded from 15 days prior to parturition with further increases occurring during the last 3 days of pregnancy. PGF2alpha metabolite levels declined gradually after parturition, reaching base line levels 15-20 days after calving.

  17. Angiogenesis in Breast Cancer and its Correlation with Estrogen, Progesterone Receptors and other Prognostic Factors

    PubMed Central

    Rani, Poonam; Kamal, Vinay; Agarwal, Prem Narayan

    2015-01-01

    Purpose: The aim of study is to evaluate angiogenesis using CD34, in estrogen, progesterone positive and negative breastcancer and to correlate the microvessel density with known histological prognostic factors, morphological type of breast carcinoma and lymph node metastasis. Materials and Methods: Twenty eight untreated cases of breast cancer were included in the study and paraffin embedded sections were obtained from representative mastectomy specimen of breast cancer patient. The sections were stained with hematoxylin and eosin stain and immunohistochemistry was performed using CD34, estrogen, progesterone, cytokeratin and epithelial membrane antigen antibody. Angiogenesis was analysed using CD 34 antibody. For statistical analysis, cases were grouped into estrogen, progesterone positive and negative receptors. Results: Mean microvessel density in ER-/PR-, ER-/ PR+, ER+/PR-, ER+/PR+ was 15.45, 14.83, 11, 10.89 respectively. A significant correlation was found between ER receptors and mean vascular density with p-value (< 0.05). A significant difference was observed in mean vascular density between the four groups comprising (p-value < 0.05). Infiltrating duct carcinoma (NOS) grade III has got the highest mean microvessel density (14.17) followed by grade II (12.93) and grade I (12.33). Conclusion: Information about prognostic factors in breast cancer patients may lead to better ways to identify those patients at high risk who might benefit from adjuvant therapies. PMID:25737993

  18. Effect of gonadal steroids on progesterone receptor, estrogen receptor, and vitellogenin expression in male turtles (Chrysemys picta).

    PubMed

    Custodia-Lora, Noemí; Novillo, Apolonia; Callard, Ian P

    2004-01-01

    Hepatic vitellogenin (vtg) is a yolk precursor protein sequestered in follicular oocytes as nutrient supply for developing embryos in nonmammalian vertebrates. In prior research studies we have demonstrated that both progesterone (P) and testosterone (T) inhibit estrogen (E)-induced vitellogenesis in the male fresh water turtle (Chrysemys picta), and have suggested that these hormones may be involved in multihormonal regulation of vitellogenesis in the female turtle. However, the modes of action of progesterone and testosterone on estrogen-induced vitellogenesis are not known. We have proposed that progesterone inhibits vitellogenesis by modulation of progesterone receptor A (PRA) or B (PRB) isoforms and/or estrogen receptor (ER) gene transcription. In this study, we compare the vitellogenic responses of reproductively inactive male turtles to estradiol 17beta in the presence of exogenous testosterone or progesterone. Northern blot analysis was used to monitor the changes in vtg mRNA, ER mRNA, and PR mRNA expression; Western blotting to determine changes in PR isoform expression and a homologous ELISA for measurement of plasma vtg. Progesterone and testosterone reduced estrogen-induced vtg mRNA expression, but plasma vtg was not significantly reduced by these steroids. PRA and PRB were transcribed even though ER mRNA could not be detected, suggesting constitutive PR expression. However, in the presence of estradiol 17beta, both PR isoforms and mRNA transcripts were increased as a correlate of ER mRNA transcription, suggesting both transcriptional and translational effects; these effects were inhibited by testosterone and progesterone treatments. Since ER mRNA was sharply reduced by both testosterone and progesterone, and estradiol 17 beta increased PR mRNA transcription and translation, it is likely that the action of progesterone in reducing vtg mRNA is indirect via down regulation of ER mRNA, thus ER. This study provides further information on the role of

  19. Precise timing for peak relaxin and decreased progesterone secretion after hysterectomy in the pig.

    PubMed

    Felder, K J; Molina, J R; Benoit, A M; Anderson, L L

    1986-10-01

    Relaxin and progesterone secretion by aging corpora lutea (days 90-120) was examined in pregnant and lactating gilts compared with that in hysterectomized animals. The length of pregnancy is about 115 days in pigs. Unmated gilts were hysterectomized on day 6 (estrus = day 0). From days 90-101, relaxin concentrations in peripheral plasma remained consistently low in pregnant gilts (range, 0.7-1.5 ng/ml) and less (P less than 0.05) than those in hysterectomized animals (range, 0.9-3.5 ng/ml). Relaxin increased abruptly (P less than 0.01) to a peak of 66 ng/ml in pregnant gilts and 37 ng/ml in hysterectomized animals. Relaxin peaked in pregnant animals at 113 +/- 0.7 days (+/- SE) and in hysterectomized gilts at 113 +/- 0.7 days; gestation length averaged 114 +/- 0.8 days. In pregnant gilts, relaxin decreased from a peak of 66 to 11 ng/ml within 1 day and remained low (less than 1.0 ng/ml) in these lactating dams until day 120. In hysterectomized gilts, peak relaxin also decreased abruptly from 37 to 4.2 ng/ml, but remained consistently greater (P less than 0.05) than that in lactating dams. Although there were abrupt shifts in relaxin concentrations within 20 min, there was no evidence for consistent episodic relaxin release between days 112-116. Plasma progesterone concentrations were consistently greater (P less than 0.05) in hysterectomized than in pregnant gilts from days 102-110. Progesterone decreased abruptly in prepartum gilts (days 111-114) from 16 to 1.2 ng/ml and remained low during lactation (0.5 ng/ml). In hysterectomized animals, it decreased abruptly on days 110-113, ranging from 20-12 ng/ml, and remained at this lower level until day 120. These results clearly indicate that a precisely timed peak release of relaxin and coincident decrease in progesterone secretion occur in unmated hysterectomized gilts at the same time as those found a few hours preceding parturition during normal pregnancy. These abrupt shifts in relaxin and progesterone secretion on

  20. Aptamer-based label-free impedimetric biosensor for detection of progesterone.

    PubMed

    Contreras Jiménez, Gastón; Eissa, Shimaa; Ng, Andy; Alhadrami, Hani; Zourob, Mohammed; Siaj, Mohamed

    2015-01-20

    Rising progesterone (P4) levels in humans due to its overconsumption through hormonal therapy, food products, or drinking water can lead to many negative health effects. Thus, the simple and accurate assessment of P4 in both environmental and clinical samples is highly important to protect public health. In this work, we present the selection, identification, and characterization of ssDNA aptamers with high binding affinity to P4. The aptamers were selected in vitro from a single-stranded DNA library of 1.8 × 10(15) oligonucleotides showing dissociation constants (KD) in the low nanomolar range. The dissociation constant of the best aptamer, designated as P4G13, was estimated to be 17 nM by electrochemical impedance spectroscopy (EIS) as well as fluorometric assay. Moreover, the aptamer P4G13 did not show cross-reactivity to analogues similar to progesterone such as 17β-estradiol (E2) and norethisterone (NET). An impedimetric aptasensor for progesterone was then fabricated based on the conformational change of P4G13 aptamer, immobilized on the gold electrode by self-assembly, upon binding to P4, which results in an increase in electron transfer resistance. Aptamer-complementary DNA (cDNA) oligonucleotides were tested to maximize the signal gain of the aptasensor after binding with progesterone. Significant signal enhancement was observed when the aptamer hybridized with a short complementary sequence at specific site was used instead of pure aptamer. This signal gain is likely due to the more significant conformational change of the aptamer-cDNA than the pure aptamer upon binding with P4, as confirmed by circular dichroism (CD) spectroscopy. The developed aptasensor exhibited a linear range for concentrations of P4 from 10 to 60 ng/mL with a detection limit of 0.90 ng/mL. Moreover, the aptasensor was applied in spiked tap water samples and showed good recovery percentages. The new selected progesterone aptamers can be exploited in further biosensing applications

  1. Effect of feeding level on progesterone concentration in early pregnant multiparous sows.

    PubMed

    Virolainen, J V; Peltoniemi, O A T; Munsterhjelm, C; Tast, A; Einarsson, S

    2005-11-01

    The effect of three feeding regimens on progesterone level was tested during early pregnancy in multiparous sows. A total of eighteen sows in their eighth parity (8.1 +/- 2.8, mean +/- S.D.) were used. During lactation the sows were fed to appetite and after weaning they received 4 kg (52 MJ) a commercial feed per day. Following ovulation, sows were allocated to one of three treatment groups and fed 2 kg/day (low feeding, LLL) or 4 kg/day (high feeding, HHH) throughout the trial or 2 kg/day for 11 days, 4 kg/day for 10 days, and 2 kg/day for the remaining days of the study (modified feeding, LHL). Blood for progesterone and cortisol analyses was collected daily throughout the study, and for luteinizing hormone (LH) assay for 12 h at 15 min intervals on days 14 and 21 of pregnancy. An adrenocorticotropic hormone (ACTH) challenge test was performed on all sows day 28 of pregnancy. Dietary treatment did not significantly affect hormonal parameters. However, progesterone concentration tended to be lower (P = 0.08) in the HHH group than in the LLL group. In the LHL group venous progesterone concentration seemed to fluctuate. No effects of feeding were observed on progesterone concentration in allantoic fluid on day 35 of pregnancy. Venous cortisol level was significantly higher (P < 0.05) during proestrus and oestrus in all groups and there was no significant difference between groups in response to ACTH challenge. The mean amplitude of LH pulses decreased significantly (P < 0.01) from days 14 to 21 of pregnancy in all groups. In addition, an interaction was found between feeding level and baseline LH concentration and also between feeding level and mean LH concentration. Embryonic recovery was highest in the LLL (69%), lowest in the HHH (45%) and moderate in the LHL (55%) group. Neither high feeding nor modified feeding provided any benefits for reproductive performance in multiparous sows. A low feeding regimen thus appears optimal for multiparous sows in early

  2. Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells.

    PubMed

    Wang, Honggang; Lee, Eun-Woo; Zhou, Lin; Leung, Peter C K; Ross, Douglas D; Unadkat, Jashvant D; Mao, Qingcheng

    2008-03-01

    Breast cancer resistance protein (BCRP) plays a significant role in drug disposition and in conferring multidrug resistance in cancer cells. Previous studies have shown that steroid hormones such as 17beta-estradiol and progesterone can affect BCRP expression in cancer cells. In this study, we investigated the molecular mechanism by which BCRP expression in human placental choriocarcinoma BeWo cells is regulated by progesterone. Transfection of the progesterone receptor (PR) isoforms PRA and PRB resulted in a similarly increased expression of PRA and PRB, respectively. However, progesterone significantly increased BCRP expression and activity only in PRB-transfected cells. This stimulatory effect of progesterone was abrogated by the PR antagonist mifepristone (RU-486). Consistently, transcriptional activity of the BCRP promoter was induced 2- to 6-fold by 10(-8) to 10(-5) M progesterone in PRB-transfected cells. Progesterone had little effect on BCRP expression and activity and transcriptional activity of the BCRP promoter in PRA-transfected cells; however, cotransfection of PRA and PRB significantly decreased the progesterone-response compared with that in cells transfected with only PRB. Mutations in a novel progesterone response element (PRE) identified between -243 to -115 bp of the BCRP promoter region significantly attenuated the progesterone-response in PRB-transfected cells, and deletion of the PRE nearly completely abrogated the progesterone effect. Specific binding of both PRA and PRB to the BCRP promoter through the identified PRE was confirmed using the electrophoretic mobility shift assay. Collectively, progesterone induces BCRP expression in BeWo cells via PRB but not PRA. PRA represses the PRB activity. Thus, PRA and PRB differentially regulate BCRP expression in BeWo cells.

  3. Pharmacokinetics of the first combination 17β-estradiol/progesterone capsule in clinical development for menopausal hormone therapy

    PubMed Central

    Pickar, James H.; Bon, Charles; Amadio, Julia M.; Mirkin, Sebastian; Bernick, Brian

    2015-01-01

    Abstract Objective: This study aims to compare the pharmacokinetics and oral bioavailability of a capsule combining 17β-estradiol and progesterone in a non–peanut oil–containing formulation with those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women. Methods: This was an open-label, balanced, randomized, single-dose, two-treatment, three-period, three-sequence, cross-over, partial-replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were randomly assigned to one of three dosing sequences of test and reference products (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference product), with each of the three periods separated by a 14-day washout. The primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the test and reference products, assessed for bioequivalence using the scaled average bioequivalence or unscaled average bioequivalence method. Safety was assessed by clinical observation, participant-reported adverse events, and laboratory data, including blood levels of hormones. Results: Sixty-six women were randomly assigned, and 62 women (94.0%) completed all three study periods. All AUC and Cmax parameters met bioequivalence criteria for all analytes (estradiol, progesterone, and estrone), except Cmax for total estrone. The extent of estradiol and progesterone absorption was similar between the test product and the reference products. Four adverse events—all considered mild and unrelated to the study drugs—were reported. Conclusions: The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation. PMID:25944519

  4. Differential phosphorylation of the progesterone receptor by insulin, epidermal growth factor, and platelet-derived growth factor receptor tyrosine protein kinases.

    PubMed

    Woo, D D; Fay, S P; Griest, R; Coty, W; Goldfine, I; Fox, C F

    1986-01-01

    Purified preparations of insulin, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) receptors were compared for their abilities to phosphorylate purified hen oviduct progesterone receptors. The specific activities of all three peptide hormone-induced receptor kinases were first defined using a synthetic tridecapeptide tyrosine protein kinase substrate. Next, equivalent ligand-activated activities of the three receptor kinases were tested for their abilities to phosphorylate hen oviduct progesterone receptor. Both the insulin and EGF receptors phosphorylated progesterone receptor at high affinity, exclusively at tyrosine residues and with maximal stoichiometries that were near unity. In contrast, the PDGF receptor did not recognize progesterone receptor as a substrate. Insulin decreased the Km of the insulin receptor for progesterone receptor subunits as substrates, but had no significant effect on Vmax values. On the other hand, EGF increased the Vmax of the EGF receptor for progesterone receptor subunits as substrates. Phosphorylation of progesterone receptor by the insulin and EGF receptor kinases differed in two additional ways. 1) EGF-activated receptor phosphorylated the 80- and 105-kDa progesterone receptor subunits to an equal extent, whereas insulin-activated receptor preferentially phosphorylated the 80-kDa subunit. 2) Phosphopeptide fingerprinting analyses revealed that while insulin and EGF receptors phosphorylated one identical major site on both progesterone receptor subunits, they differed in their specificities for other sites. PMID:3001059

  5. Progesterone Increases the Release of Brain-Derived Neurotrophic Factor from Glia via Progesterone Receptor Membrane Component 1 (Pgrmc1)-Dependent ERK5 Signaling

    PubMed Central

    Su, Chang; Cunningham, Rebecca L.; Rybalchenko, Nataliya

    2012-01-01

    Progesterone (P4) is cytoprotective in various experimental models, but our understanding of the mechanisms involved is still incomplete. Our laboratory has implicated brain-derived neurotrophic factor (BDNF) signaling as an important mediator of P4's protective actions. We have shown that P4 increases the expression of BDNF, an effect mediated by the classical P4 receptor (PR), and that the protective effects of P4 were abolished using inhibitors of Trk receptor signaling. In an effort to extend our understanding of the interrelationship between P4 and BDNF signaling, we determined whether P4 influenced BDNF release and examined the role of the classical PR and a putative membrane PR, progesterone receptor membrane component-1 (Pgrmc1), as mediators of this response. Given recent data from our laboratory that supported the role of ERK5 in BDNF release, we also tested whether P4-induced BDNF release was mediated by ERK5. In this study, we found that P4 and the membrane-impermeable P4 (P4-BSA) both induced BDNF release from cultured C6 glial cells and primary astrocytes. Both these cells lack the classical nuclear/intracellular PR but express high levels of membrane-associated PR, including Pgrmc1. Using RNA interference-mediated knockdown of Pgrmc1 expression, we determined that P4-induced BDNF release was dependent on the expression of Pgrmc1, although pharmacological inhibition of the PR failed to alter the effects of P4. Furthermore, the BDNF release elicited by P4 was mediated by ERK5, and not ERK1/2. Collectively, our data describe that P4 elicits an increase in BDNF release from glia via a Pgrmc1-induced ERK5 signaling mechanism and identify Pgrmc1 as a potential therapeutic target for future hormone-based drug development for the treatment of such degenerative diseases as Alzheimer's disease as well as other diseases wherein neurotrophin dysregulation is noted. PMID:22778217

  6. Role of the short isoform of the progesterone receptor in breast cancer cell invasiveness at estrogen and progesterone levels in the pre- and post-menopausal ranges

    PubMed Central

    McFall, Thomas; Patki, Mugdha; Rosati, Rayna; Ratnam, Manohar

    2015-01-01

    Overexpression of the progesterone receptor (PR) isoform A (PR-A) is a negative prognosticator for estrogen receptor (ER)-positive breast cancer but in vitro studies have implicated PR-B in progestin-induced invasiveness. As estrogen is known to suppress invasiveness and tumor progression and as the in vitro studies were conducted in models that either lacked ER or excluded estrogen, we examined the role of PR isoforms in the context of estrogen signaling. Estrogen (< 0.01nM) strongly suppressed invasiveness in various ER+ model cell lines. At low (< 1nM) concentrations, progestins completely abrogated inhibition of invasiveness by estrogen. It was only in a higher (5 nM — 50 nM) concentration range that progestins induced invasiveness in the absence of estrogen. The ability of low dose progestins to rescue invasiveness from estrogen regulation was exclusively mediated by PR-A, whereas PR-B mediated the estrogen-independent component of progestin-induced invasiveness. Overexpression of PR-A lowered the progestin concentration needed to completely rescue invasiveness. Among estrogen-regulated genes, progestin/PR-A counter-regulated a distinctive subset, including breast tumor progression genes (e.g., HES1, PRKCH, ELF5, TM4SF1), leading to invasiveness. In this manner, at relatively low hormone concentrations (corresponding to follicular stage and post-menopausal breast tissue or plasma levels), progesterone influences breast cancer cell invasiveness by rescuing it from estrogen regulation via PR-A, whereas at higher concentrations the hormone also induces invasiveness independent of estrogen signaling, through PR-B. The findings point to a direct functional link between PR-A and progression of luminal breast cancer in the context of the entire range of pre- and post-menopausal plasma and breast tissue hormone levels. PMID:26356672

  7. Progesterone, Inflammatory Cytokine (TNF-α), and Oxidative Stress (H2O2) Regulate Progesterone Receptor Membrane Component 1 Expression in Fetal Membrane Cells.

    PubMed

    Meng, Yan; Murtha, Amy P; Feng, Liping

    2016-09-01

    Progesterone receptor membrane component 1 (PGRMC1) is an important novel mediator of progesterone (P4) function in fetal membrane cells. We demonstrated previously that PGRMC1 is differentially expressed in fetal membranes among pregnancy subjects and diminished in preterm premature rupture of membrane subjects. In the current study, we aim to elucidate whether PGRMC1 expression is regulated by P4, tumor necrosis factor α (TNF-α), and H2O2 in fetal membrane cells. Primary cultured membrane cells were serum starved for 24 hours followed by treatments of P4, 17 hydroxyprogesterone caproate, and medroxyprogesterone 17 acetate (MPA) at 10(-7) mol/L with ethanol as vehicle control; TNF-α at 10, 20, and 50 ng/mL with phosphate-buffered saline (PBS) as control; and H2O2 at 10 and 100 μmol/L with culture media as control for 24, 48, and 72 hours. The messenger RNA (mRNA) and protein expression of PGRMC1 was quantified using polymerase chain reaction and Western blotting, respectively. We found that PGRMC1 protein expression was regulated by MPA, TNF-α, and H2O2 in a dose-dependent manner. This regulation is also specific to the type of cell (amnion, chorion, or decidua). The upregulation of PGRMC1 by MPA might be mediated through glucocorticoid receptor (GR) demonstrated using amnion and chorion cells model with GR knockdown by specific small interfering RNA transfection. The mRNA expression of PGRMC1 was decreased by H2O2 (100 μmol/L) treatment in amnion cells, which might ultimately result in downregulation of PGRMC1 protein as our data demonstrated. None of other treatments changed PGRMC1 mRNA level in these cells. We conclude that these stimuli act as regulatory factors of PGRMC1 in a cell-specific manner. PMID:26919974

  8. Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes.

    PubMed

    Wallace, J M; Bourke, D A; Da Silva, P; Aitken, R P

    2003-10-01

    Overnourishing adolescent ewes throughout pregnancy promotes maternal tissue synthesis at the expense of placental growth, which in turn leads to a major decrease in lamb birth weight. As maternal dietary intakes are inversely related to peripheral progesterone concentrations in these adolescent dams, it was hypothesized that sup-optimal progesterone concentrations in overnourished dams may compromise the growth of the differentiating conceptus resulting in fewer uterine caruncles being occupied and, hence, fewer placentomes formed. This hypothesis was tested by supplementing overnourished adolescent dams with exogenous progesterone during early pregnancy and determining the impact on pregnancy outcome at term. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. After transfer of embryos, ewes were offered a moderate or high amount of a complete diet (n=11 per group). A further high intake group received a progesterone supplement each day from day 5 to day 55 of gestation (term=145 days) to restore circulating progesterone concentrations to moderate values throughout the first third of pregnancy (n=11). For ewes establishing pregnancies (n=7 per group), live weight gain during the first 100 days of gestation was 66+/-4, 323+/-17 and 300+/-7 g per day, body condition score at term was 2.1+/-0.05, 3.0+/-0.08 and 3.1+/-0.07 units and the duration of gestation after spontaneous delivery was 148+/-1.7, 144+/-0.8 and 143+/-0.8 days for the moderate intake, high intake and high intake plus progesterone groups, respectively. At delivery, fetal cotyledon mass (136+/-12.1 versus 57+/-8.2g, P<0.001) and lamb birth weight (5164+/-151 versus 2893+/-381 g, P<0.001) were higher in moderate intake than in high intake dams. Progesterone supplementation restored circulating concentrations to moderate values during the first third of gestation. Lamb birth weight in the high

  9. Effect of progesterone, mifepristone, and estrogen treatment during early pregnancy on conceptus development and uterine capacity in Swine.

    PubMed

    Vallet, J L; Christenson, R K

    2004-01-01

    A series of experiments was performed to investigate the influence of progesterone at Days 2 and 3 of pregnancy on conceptus development and uterine capacity. In experiment 1, unilaterally hysterectomized-ovariectomized (UHO) white crossbred gilts were given no treatment, estradiol valerate (5 mg given on Days 11 and 12), or progesterone (200 mg/day on Days 2 and 3 after mating). On Day 105 of pregnancy, each fetus and its associated placenta were weighed, and the number of live and dead fetuses was recorded for each litter. Early progesterone treatment reduced (P < 0.05) litter size (a measure of uterine capacity in UHO gilts). In experiment 2, intact white crossbred gilts were mated, given no treatment or progesterone treatment on Days 2 and 3 of pregnancy, and farrowed. Progesterone treatment decreased (P < 0.05) pregnancy rates. In pregnant gilts, progesterone had no effect on the number of live or stillborn piglets at birth, and gestation length was decreased (P < 0.05). Progesterone treatment did not affect the number of large or small piglets. In experiment 3, intact gilts were mated at estrus and then received 1). no treatment or treatment with 2). 100 mg, 3). 200 mg, or 4). 400 mg mifepristone (also known as RU486) on Day 2 of pregnancy. On Day 11 of pregnancy, both uterine horns were flushed, the number and diameter of each conceptus was recorded, and the flushed material was assayed for total protein and acid phosphatase. The 400 mg mifepristone treatment decreased conceptus diameter (P < 0.05) and total protein (P = 0.06) in the uterine flushings. In experiment 4, UHO gilts were mated at estrus, injected with either corn oil (control) or mifepristone (400 mg) on Day 2 of pregnancy, and killed on Day 105 of pregnancy, and the number and weight of live fetuses and placentas was recorded. In contrast to the effect of progesterone treatment, mifepristone decreased uterine capacity by decreasing the number of small conceptuses. These data suggest that

  10. Correlation of Serum CA-125 and Progesterone Levels with Ultrasound Markers in The Prediction of Pregnancy Outcome in Threatened Miscarriage

    PubMed Central

    Al Mohamady, Maged; Fattah, Ghada Abdel; Elkattan, Eman; Bayoumy, Rasha; Hamed, Dalia Ahmed

    2016-01-01

    Background The aim of this study was to evaluate the relationship between ultrasonographic findings and serum progesterone and cancer antigen-125 (CA-125) levels in threatened miscarriage and to predict pregnancy outcome. Materials and Methods In a prospective comparative case-control study, serum CA-125 and progesterone levels were measured for 100 pregnant women with threatened miscarriage who attended the outpatient clinic or the causality department of Obstetrics and Gynecology at Kasr El-Aini Hospital, Giza, Egypt, during the period from March 2013 to October 2013. Ultrasound was performed for fetal viability, crown-rump length (CRL), gestational sac diameter (GSD) and fetal heart rate (FHR). The patients were followed up and divided into two groups based on the outcome: 20 women who miscarried (group 1), and 80 women who continued pregnancy (group 2). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were tested for CA-125 and progesterone levels in prediction of the pregnancy outcome. Correlation of these chemical markers with the ultrasound markers was also examined. Results In the group that miscarried, CA-125 level was significantly higher (P<0.001) and serum progesterone level was significantly lower (P<0.001). For prediction of the outcome of pregnancy, the cut-off limit of 31.2 IU/ml for CA-125 level yielded sensitivity, specificity and an overall accuracy of 96.2, 100 and 99.4% respectively. The cut-off limit of 11.5 ng/ml for progesterone level yielded sensitivity, specificity and an overall accuracy of 97.5, 100 and 99.8% respectively. CA-125 level had a negative correlation with progesterone level and FHR levels (r=-0.716, P<0.001) and (r=-0.414, P<0.001) respectively. Serum progesterone level correlated with GSD (r=0.521, P<0.001) and with CRL (r=0.407, P<0.001) and FHR (r=0.363, P<0.001). CA-125 level was significantly higher in the group that showed hematoma as compared with the

  11. Progesterone and estradiol-17β as a potential method for pregnancy diagnosis in the collared peccary (Pecari tajacu).

    PubMed

    Mayor, Pedro; Guimarães, Diva Anelie; López-Béjar, Manel

    2012-12-01

    In this study, the period of pregnancy of nine collared peccary females has been monitored through the analysis of serum progesterone and estradiol-17β profiles. Serum concentrations of progesterone increased by Day 4 after conception, reaching concentrations of 33.4±5.6 ng/mL on Day 10. Between Days 10 and 130 progesterone values were maintained between 20 and 60 ng/mL. In the collared peccary, embryonic estradiol synthesis is first observed in the systemic circulation by Day 15 of pregnancy. Between Days 0 and 50 of pregnancy, average estradiol-17β concentrations were between 0 and 30 pg/mL. From Day 75 of pregnancy onwards, estradiol concentrations were constantly increasing, reaching maximum concentrations (131.4±40.8 pg/mL) on the day of parturition. The combined study of serum progesterone and estradiol-17β concentrations as a potential method for early pregnancy diagnosis presented the best overall accuracy (73%) when the threshold was established at 20 ng/mL serum progesterone and 20 pg/mL serum estradiol. Nevertheless, the accuracy for diagnosing pregnancy of females at mid and late pregnancy was 78% and 95%, respectively. The analysis of the sexual hormones during pregnancy could be a useful tool as a potential pregnancy diagnosis and an efficient predictor of the day of parturition in the captive collared peccary.

  12. Longitudinal progesterone profiles in baleen from female North Atlantic right whales (Eubalaena glacialis) match known calving history.

    PubMed

    Hunt, Kathleen E; Lysiak, Nadine S; Moore, Michael J; Rolland, Rosalind M

    2016-01-01

    Reproduction of mysticete whales is difficult to monitor, and basic parameters, such as pregnancy rate and inter-calving interval, remain unknown for many populations. We hypothesized that baleen plates (keratinous strips that grow downward from the palate of mysticete whales) might record previous pregnancies, in the form of high-progesterone regions in the sections of baleen that grew while the whale was pregnant. To test this hypothesis, longitudinal baleen progesterone profiles from two adult female North Atlantic right whales (Eubalaena glacialis) that died as a result of ship strike were compared with dates of known pregnancies inferred from calf sightings and post-mortem data. We sampled a full-length baleen plate from each female at 4 cm intervals from base (newest baleen) to tip (oldest baleen), each interval representing ∼60 days of baleen growth, with high-progesterone areas then sampled at 2 or 1 cm intervals. Pulverized baleen powder was assayed for progesterone using enzyme immunoassay. The date of growth of each sampling location on the baleen plate was estimated based on the distance from the base of the plate and baleen growth rates derived from annual cycles of stable isotope ratios. Baleen progesterone profiles from both whales showed dramatic elevations (two orders of magnitude higher than baseline) in areas corresponding to known pregnancies. Baleen hormone analysis shows great potential for estimation of recent reproductive history, inter-calving interval and general reproductive biology in this species and, possibly, in other mysticete whales.

  13. Progesterone receptor A stability is mediated by glycogen synthase kinase-3β in the Brca1-deficient mammary gland.

    PubMed

    Wang, Shaohui; Li, Ying; Hsu, Pang-Hung; Lee, Sou-Ying; Kim, Yoon; Lee, Eva Y-H P

    2013-09-01

    Germ line mutations of the BRCA1 gene increase the risk of breast and ovarian cancer, but the basis of this tissue-specific tumor predisposition is not fully understood. Previously, we reported that the progesterone receptors are stabilized in Brca1-deficient mammary epithelial cells, and treating with anti-progesterone delays mammary tumorigenesis in Brca1/p53 conditional knock-out mice, suggesting that the progesterone has a critical role in breast carcinogenesis. To further explore how the stability of progesterone receptor is modulated, here, we have found that glycogen synthase kinase (GSK)-3β phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination. GSK-3β-mediated phosphorylation of serine 390 in PR-A regulates its subsequent ubiquitination and protein stability. Expression of PR-A(S390A) mutant in the human breast epithelial cells, MCF-10A, results in enhanced proliferation and formation of aberrant acini structure in the three-dimensional culture. Consistently, reduction of phosphorylation of serine 390 of PR-A and GSK-3β activity is observed in the Brca1-deficient mammary gland. Taken together, these results provide important aspects of tissue specificity of BRCA1-mediated suppression of breast carcinogenesis.

  14. Increased yolk progesterone interferes with prenatal auditory learning and elevates emotional reactivity in bobwhite quail (Colinus virginianus) chicks.

    PubMed

    Herrington, Joshua; Vallin, Claudia; Lickliter, Robert

    2015-03-01

    Avian eggs contain maternally derived hormones, including testosterone and progesterone. Little is currently known about the effects of these hormones on early behavioral development. We assessed the effects of elevated levels of progesterone levels on prenatal perceptual learning and postnatal emotional reactivity in Northern bobwhite quail. Prior to incubation, eggs received an injection of either progesterone (P) or oil vehicle (V). In P eggs, levels of progesterone were elevated two standard deviations above the mean based on ELISA analysis of progesterone yolk concentrations from a previous study. A third group of eggs served as controls and received no injection (C). Chicks hatched from P eggs displayed elevated levels of emotional reactivity compared to V and C chicks in a tonic immobility task and a hole-in-the-wall emergence task. Chicks from P eggs also failed to demonstrate a preference for a familiarized bobwhite maternal call that had been presented prenatally. In contrast, the V and C chicks demonstrated a significant preference for the familiarized maternal call following hatching, indicating prenatal auditory learning. Our results are consistent with previous findings from precocial birds demonstrating that hormones of maternal origin can influence prenatal perceptual learning as well as emotional reactivity in the period following hatching..

  15. Notch1 Is Regulated by Chorionic Gonadotropin and Progesterone in Endometrial Stromal Cells and Modulates Decidualization in Primates

    PubMed Central

    Afshar, Yalda; Miele, Lucio

    2012-01-01

    No other tissue in the body undergoes such a vast and extensive growth and remodeling in a relatively short period of time as the primate endometrium. Endometrial integrity is coordinated by ovarian hormones, namely, estrogens, progesterone, and the embryonic hormone chorionic gonadotropin (CG). These regulated events modulate the menstrual cycle and decidualization. The Notch family of transmembrane receptors regulate cellular proliferation, differentiation, and apoptosis, cellular processes required to maintain endometrial integrity. In two primate models, the human and the simulated pregnant baboon model, we demonstrated that Notch1 is increased during the window of uterine receptivity, concomitant with CG. Furthermore, CG combined with estrogens and progesterone up-regulate the level of Notch1, whereas progesterone increases the intracellular transcriptionally competent Notch1, which binds in a complex with progesterone receptor. Inhibition of Notch1 prevented decidualization, and alternatively, when decidualization is biochemically recapitulated in vitro, Notch1 is down-regulated. A focused microarray demonstrated that the Notch inhibitor, Numb, dramatically increased when Notch1 decreased during decidualization. We propose that in the endometrium, Notch has a dual role during the window of uterine receptivity. Initially, Notch1 mediates a survival signal in the uterine endometrium in response to CG from the implanting blastocyst and progesterone, so that menstrual sloughing is averted. Subsequently, Notch1 down-regulation may be critical for the transition of stromal fibroblast to decidual cells, which is essential for the establishment of a successful pregnancy. PMID:22535768

  16. Stress, rejection, and hormones: Cortisol and progesterone reactivity to laboratory speech and rejection tasks in women and men

    PubMed Central

    Gaffey, Allison E.; Wirth, Michelle M.

    2014-01-01

    Stress and social rejection have important impacts on health. Among the mechanisms implicated are hormonal systems such as the hypothalamic-pituitary-adrenal (HPA) axis, which produces cortisol in humans. Current research employs speech stressors and social rejection stressors to understand hormonal responses in a laboratory setting. However, it is not clear whether social rejection stressors elicit hormonal reactivity. In addition to cortisol, progesterone has been highlighted as a potential stress- and affiliation-related hormone in humans. In the present study, 131 participants (70 men and 61 women) were randomly assigned to be exposed to one of four conditions: standardized speech stressor; speech control; social rejection task; or a control (inclusion) version of the social rejection task. Saliva samples were collected throughout the study to measure cortisol and progesterone. As hypothesized, we found the expected increase in cortisol in the speech stressor, and we also found that the social rejection task did not increase cortisol, underscoring the divergence between unpleasant experiences and HPA axis activity. However, we did not find evidence for progesterone increase either during the speech- or social rejection tasks. Compared with past studies on progesterone and stress in humans, the present findings present a mixed picture. Future work is needed to delineate the contexts and types of manipulations which lead to progesterone increases in humans. PMID:25580228

  17. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-04-01

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion. PMID:27032848

  18. Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

    SciTech Connect

    Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

    1986-03-01

    Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development.

  19. Preterm Birth Prevention: Effects of Vaginal Progesterone Administration on Blood Flow Impedance in Uterine-Fetal Circulation by Doppler Sonography

    PubMed Central

    Vafaei, Homeira; Zamanpour, Tarlan; Shahraki, Hadi Raeisi

    2016-01-01

    Objective: The present study aimed to evaluate the effect of vaginal progesterone administration on maternal and fetal circulation to prevent preterm birth. Methods: The present prospective study was conducted on 35 women with singleton pregnancy at 18–33 weeks of gestation, who presented with at least one episode of preterm labor or asymptomatic short cervix, or past medical history of preterm birth. Doppler flow and Pulsatility Index (PI) assessment of the umbilical artery, fetal middle cerebral artery, uterine arteries, and ductusvenosus were performed before and 72 h after vaginal progesterone administration. Results: Results showed a significant reduction in the PI of the uterine artery following progesterone administration. Nevertheless, no significant changes were observed in the PI of other vessels. No significant difference was found in Doppler flow parameters in any of the examined vessels before or after progesterone treatment in women with Preterm Labor Pain (PLP). Yet, a statistically significant association was observed between short cervix complication in the current pregnancy and medical history of PLP in the previous pregnancy. Conclusion: Treatment with vaginal progesterone reduced the PI in the uterine arteries in the second and third trimesters of pregnancy. Thus, this medication may have useful vasodilatory effects on uterine-fetal vessels. PMID:26925899

  20. Progesterone has rapid positive feedback actions on LH release but fails to reduce LH pulse frequency within 12 h in estradiol-pretreated women.

    PubMed

    Hutchens, Eleanor G; Ramsey, Katherine A; Howard, Louisa C; Abshire, Michelle Y; Patrie, James T; McCartney, Christopher R

    2016-08-01

    In women, progesterone suppresses luteinizing hormone (LH) (gonadotropin-releasing hormone) pulse frequency, but how rapidly this occurs is unknown. In estradiol-pretreated women in the late follicular phase, progesterone administration at 1800 did not slow sleep-associated LH pulse frequency. However, mechanisms controlling LH pulse frequency may differ according to sleep status; and we thus hypothesized that progesterone acutely suppresses waking LH pulse frequency. This was a randomized, double-blind, crossover study of LH secretory responses to progesterone versus placebo administered at 0600. We studied 12 normal women in the late follicular phase (cycle days 7-11), pretreated with 3 days of transdermal estradiol (0.2 mg/day). Subjects underwent a 24-h blood sampling protocol (starting at 2000) and received either 100 mg oral micronized progesterone or placebo at 0600. In a subsequent menstrual cycle, subjects underwent an identical protocol except that oral progesterone was exchanged for placebo or vice versa. Changes in 10-h LH pulse frequency were similar between progesterone and placebo. However, mean LH, LH pulse amplitude, and mean follicle-stimulating hormone exhibited significantly greater increases with progesterone. Compared to our previous study (progesterone administered at 1800), progesterone administration at 0600 was associated with a similar increase in mean LH, but a less pronounced increase in LH pulse amplitude. We conclude that, in estradiol-pretreated women in the late follicular phase, a single dose of progesterone does not suppress waking LH pulse frequency within 12 h, but it acutely amplifies mean LH and LH pulse amplitude - an effect that may be influenced by sleep status and/or time of day. PMID:27535481

  1. The stimulation of respiration by progesterone in ovariectomized cat is mediated by an estrogen-dependent hypothalamic mechanism requiring gene expression.

    PubMed

    Bayliss, D A; Cidlowski, J A; Millhorn, D E

    1990-01-01

    The central site of action and the cellular mechanism by which progesterone stimulates respiration were studied in ovariectomized cats that were anesthetized, paralyzed, and ventilated and in which respiratory sensory feedback mechanisms were either eliminated or controlled. Phrenic nerve activity served as an index of central respiratory output. Progesterone did not stimulate respiration in ovariectomized cats not pretreated with estrogen. In contrast, repeated doses of progesterone (0.1-1.0 microgram/kg, iv, cumulative) caused a sustained (greater than 45 min) dose-dependent facilitation of phrenic nerve activity in animals primed 3 days before study with 17 beta-estradiol (20 micrograms/kg, sc). Estrogen exposure is, therefore, a prerequisite for the respiratory response to progesterone in ovariectomized cats. This estrogen-dependent respiratory response to progesterone was attenuated in animals pretreated with either the estrogen receptor antagonist CI628 or the progesterone receptor antagonist RU486, indicating that the respiratory response is mediated by both estrogen and progesterone receptors. Inhibitors of protein (anisomycin) and RNA (actinomycin-D) synthesis caused a diminution of the respiratory response to progesterone, implicating a requirement for gene expression in the response. Midcollicular decerebration (which removed the diencephalon) attenuated, whereas decortication (which spared the diencephalon) did not affect the respiratory response to progesterone. Thus, the diencephalon appears to be a critical neuroanatomical substrate for the response. These results indicate that the respiratory response to progesterone is mediated, at a hypothalamic site, via a genomic mechanism with characteristics consistent with the prototypic mechanism for progesterone actions. PMID:2294002

  2. Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

    PubMed

    Silva, Anatildes Feitosa; Sousa, Diego Silveira; Medeiros, André Macêdo; Macêdo, Priscila Tavares; Leão, Anderson Henrique; Ribeiro, Alessandra Mussi; Izídio, Geison Souza; Silva, Regina Helena

    2016-10-01

    Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women. PMID:27208614

  3. Pregnancy-specific protein B and progesterone concentrations in French Alpine goats throughout gestation.

    PubMed

    Humblot, P; De Montigny, G; Jeanguyot, N; Tetedoie, F; Payen, B; Thibier, M; Sasser, R G

    1990-05-01

    The 34 French Alpine dairy goats originated from a single flock and were artificially inseminated 44 h after synchronization of oestrus. They were bled daily at the jugular vein from 15 to 27 days after AI. An early pregnancy diagnosis by RIA of progesterone concentration was performed 21 days after AI. In pregnant goats (greater than 1.5 ng progesterone/ml) daily sampling was extended until 30 days after AI and, from those, 9 were bled every 2 weeks until the end of pregnancy and at 50 and 63 days post partum. Pregnancy-specific protein B (PSPB) was also assayed. The kidding rate was 67.6% (23/34). PSPB concentrations (ng/ml) in pregnant goats were significantly different from those of non-pregnant goats at 24 days after AI (0.82 +/- 0.18 vs 1.78 +/- 0.19; mean +/- s.e.m.) and rose to 40 ng/ml at the end of pregnancy. From Day 25 and throughout gestation, females with 2 fetuses had higher PSPB concentrations than did those with a single fetus (P less than 0.05). In the 2 goats exhibiting late embryonic mortality according to progesterone concentrations, one had a PSPB profile very similar to those of pregnant goats until 30 days while the other did not show any elevation of PSPB concentration. It is concluded that PSPB profiles in goats are similar to those found in cows throughout pregnancy and that PSPB RIA may be useful for pregnancy diagnosis or diagnosis of late embryonic mortality. PMID:1695679

  4. Intravaginal impedance and sexual behavior of ovariectomized goats given estrogen alone or in combination with progesterone.

    PubMed

    Imwalle, D B; Lehrer, A R; Katz, L S

    2007-08-01

    Intravaginal impedance (IVI) fluctuates during the goat estrous cycle. To understand which ovarian steroids are responsible for IVI changes and whether IVI variations are associated with precopulatory and copulatory behaviors, 8 ovariectomized females were assigned to 4 treatments in a 4 x 4 Latin square replicated over four 8-d periods. The treatments were as follows: progesterone plus estradiol-17beta (P4 + E2), oil plus estradiol-17beta (E2), progesterone plus oil (P4), or oil (OIL). Daily IVI measurements at the vagino-cervical junction were taken at 1 and 70 KHz. Progesterone was given on d 2 and 3. Estradiol was given in the evening of d 5. On d 1 to 8, goats were group-exposed to a sexually experienced male and observed for the expression of sexual behaviors. On d 6 and 7, IVI was less when goats received P4 + E2 or E2 compared with goats given P4 or OIL (P < 0.05). Impedance measured at 1 kHz tended to remain lower on d 8 in P4 + E2-treated females compared with those given P4 or OIL (P < 0.055). Like previous results, P4 + E2 or E2 treatment induced behavioral estrus; 5 of 8 P4 + E2-treated and 5 of 8 E2-treated females were sexually receptive on d 6. On d 7, although IVI remained low and 2 of 8 P4 + E2-treated goats and 4 of 8 E2-treated goats remained sexually receptive, no additional females were in estrus. No IVI decreases and no estrous behavior were observed in goats given P4 or OIL. This experiment demonstrated that E2 initiates the periestrous drop in IVI, and P4 may delay baseline return. PMID:17504954

  5. Plasma prolactin, growth hormone and progesterone concentrations in pseudopregnant, hysterectomized and pregnant goats.

    PubMed

    Kornalijnslijper, J E; Kemp, B; Bevers, M M; van Oord, H A; Taverne, M A

    1997-12-01

    Jugular plasma prolactin (PRL), growth hormone (GH) and progesterone (P4) levels were estimated in goats under three different conditions with prolonged luteal function (P4 > or = 1 ng/ml): pseudopregnant animals (n = 4), goats hysterectomized during early pregnancy (n = 4) and does with normal pregnancy (n = 4). Mean duration (+/- S.E.M.) of luteal phases were 189 +/- 20, 171 +/- 10, and 147 +/- 2 days in the three groups, respectively. Until day 120, mean PRL levels were below 150 ng/ml in each group. After day 120 of the luteal phase, PRL concentrations were significantly higher than before, but continued to increase up to 800 ng/ml only in pregnant animals around parturition. Mean GH levels varied between 2 and 3 ng/ml in animals of each group during the luteal phase. Only after parturition, a significant elevation occurred. P4 levels in pseudopregnant animals were significantly lower than in the other two groups between days 10 and 55, and showed a gradual but continuous decline towards the end of the luteal phase. After hysterectomy of early pregnant animals, P4 concentrations decreased to levels measured in pseudopregnant animals but were significantly higher again as compared to pseudopregnant animals between days 121 and 150. It is concluded that a pseudopregnant condition, characterized by intrauterine fluid accumulation, is not related to increased plasma PRL and GH concentrations. The low and gradually decreasing plasma progesterone levels in the pseudopregnant animals probably reflect the absence of a luteotrophic stimulus by the conceptus. The progesterone profile in the animals that were hysterectomized during early pregnancy suggests that the corpora lutea of these does have been permanently changed by the presence of the conceptus during the first weeks of the luteal phase. PMID:9505110

  6. Response of prepubertal ewes primed with monensin or progesterone to administration of FSH.

    PubMed

    Sumbung, F P; Williamson, P; Carson, R S

    1987-11-01

    Prepubertal ewe lambs were treated with FSH after progesterone priming for 12 days (Group P), monensin supplementation for 14 days (Group M) or a standard diet (Group C). Serial blood samples were taken for LH and progesterone assay, and ovariectomy was performed on half of each group 38-52 h after start of treatment to assess ovarian function, follicular steroid production in vitro and the concentration of gonadotrophin binding sites in follicles. The remaining ewe lambs were ovariectomized 8 days after FSH treatment to determine whether functional corpora lutea were present. FSH treatment was followed by a preovulatory LH surge which occurred significantly later (P less than 0.05) and was better synchronized in ewes in Groups P and M than in those in Group C. At 13-15 h after the LH surge significantly more large follicles were present on ovaries from Group P and M ewes than in Group C. Follicles greater than 5 mm diameter from ewes in Groups P and M produced significantly less oestrogen and testosterone and more dihydrotestosterone, and had significantly more hCG binding sites, than did similar-sized follicles from Group C animals. Ovariectomy on Day 8 after the completion of FSH treatment showed that ewes in Groups P and M had significantly greater numbers of functional corpora lutea. These results indicate that, in prepubertal ewes, progesterone priming and monensin supplementation may delay the preovulatory LH surge, allowing follicles developing after FSH treatment more time to mature before ovulation. This may result in better luteinization of ruptured follicles in these ewes, with the formation of functional corpora lutea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3123655

  7. Androstenedione interferes in luteal regression by inhibiting apoptosis and stimulating progesterone production.

    PubMed

    Goyeneche, Alicia A; Calvo, Virginia; Gibori, Geula; Telleria, Carlos M

    2002-05-01

    Androgens, in concert with lactogenic hormones, contribute to the maintenance of function of the corpus luteum (CL) in pregnant rats. Whereas some of the androgenic actions in the CL are clearly mediated by intracrine conversion to estrogen, pure androgenic effects are also implicated in the regulation of this transient endocrine gland. In this report, we have established, to our knowledge for the first time, the expression of androgen receptor (AR) mRNA and protein throughout gestation in the rat CL. We have found that the AR remains expressed in the CL of gestation on Day 4 postpartum and becomes expressed in the newly formed CL after postpartum ovulation. An AR immunoreactive protein was identified in the CL of pregnancy as well as in prostate and epididymis, which were used as positive controls. The luteal AR protein had mainly nuclear localization, yet some diffuse cytoplasmic staining was also observed. Moreover, we have established that androstenedione, the main circulating androgen in pregnant rats, significantly reduces the decline in luteal weight observed during postpartum structural regression. This effect was correlated with a decrease in the number of cells undergoing apoptosis and with enhanced levels of circulating progesterone. In addition, in vivo administration of androstenedione delayed the occurrence of DNA fragmentation in postpartum CL incubated in serum-free conditions. Finally, we have shown that the interference with apoptosis in vitro elicited by androstenedione is accompanied by an increased capacity of the CL to secrete progesterone. In summary, the results of this study have established that the rat CL expresses AR throughout pregnancy and after parturition, and they have defined a potential role for androstenedione in opposing postpartum luteal regression through inhibition of apoptosis and stimulation of progesterone production.

  8. Dysregulation of Uterine Signaling Pathways in Progesterone Receptor-Cre Knockout of Dicer

    PubMed Central

    Andreu-Vieyra, Claudia V.; Kim, Tae Hoon; Jeong, Jae-Wook; Hodgson, Myles C.; Chen, Ruihong; Creighton, Chad J.; Lydon, John P.; Gunaratne, Preethi H.; DeMayo, Francesco J.; Matzuk, Martin M.

    2012-01-01

    Epithelial-stromal interactions in the uterus are required for normal uterine functions such as pregnancy, and multiple signaling pathways are essential for this process. Although Dicer and microRNA (miRNA) have been implicated in several reproductive processes, the specific roles of Dicer and miRNA in uterine development are not known. To address the roles of miRNA in the regulation of key uterine pathways, we generated a conditional knockout of Dicer in the postnatal uterine epithelium and stroma using progesterone receptor-Cre. These Dicer conditional knockout females are sterile with small uteri, which demonstrate significant defects, including absence of glandular epithelium and enhanced stromal apoptosis, beginning at approximately postnatal d 15, with coincident expression of Cre and deletion of Dicer. Specific miRNA (miR-181c, −200b, −101, let-7d) were down-regulated and corresponding predicted proapoptotic target genes (Bcl2l11, Aldh1a3) were up-regulated, reflecting the apoptotic phenomenon. Although these mice had normal serum hormone levels, critical uterine signaling pathways, including progesterone-responsive genes, Indian hedgehog signaling, and the Wnt/β-catenin canonical pathway, were dysregulated at the mRNA level. Importantly, uterine stromal cell proliferation in response to progesterone was absent, whereas uterine epithelial cell proliferation in response to estradiol was maintained in adult uteri. These data implicate Dicer and appropriate miRNA expression as essential players in the regulation of multiple uterine signaling pathways required for uterine development and appropriate function. PMID:22798293

  9. Estrogen and progesterone modulate [35S]GTPgammaS binding to nociceptin receptors.

    PubMed

    Quesada, Arnulfo; Micevych, Paul

    2008-01-01

    Sex steroids modulate reproduction by altering the response of steroid-activated opioid circuits in the hypothalamus and limbic system, by inducing release of endogenous opioids and activation of their cognate receptors. Many studies have concentrated on steroid regulation of exogenous opioid peptides, but steroids also have important actions on opioid receptors inducing receptor trafficking. Opioid receptors are G protein-coupled receptors and their activation catalyzes the exchange of GTP for GDP initiating intracellular signaling cascades. Kinetics of G protein activation were studied using [(35)S]GTPgammaS binding. Catalytic amplification, the number of G proteins activated per occupied receptor, was used as a measure of receptor/transducer amplification. The present study examined whether estrogen and progesterone treatment altered the kinetics of nociceptin opioid receptor (ORL1) in plasma membranes from the medial preoptic area and mediobasal hypothalamus. These hypothalamic regions are important in the gonadal steroid hormone regulation of sexual receptivity. In the mediobasal hypothalamus, estrogen increased ORL1 (B(max)) receptor number 2-fold and maximal GTPgammaS binding (E(max)) 3.9-fold. Subsequent progesterone treatment further increased ORL1 E(max )6.9-fold above baseline, despite a 2-fold decrease in the catalytic amplification factor. In the medial preoptic area, estrogen alone did not increase E(max), but both estrogen and progesterone were able to increase ORL1 B(max) 2.2-fold and E(max) 3-fold, despite having a 3-fold decrease in the catalytic amplification factor. These effects are interesting because they indicate actions of steroids that increase the number of ORL1 but decrease the catalytic amplification suggesting that the steroid effects on opioid receptors are complex and may involve modulation by other signals. PMID:18212517

  10. Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone.

    PubMed

    Silva, Anatildes Feitosa; Sousa, Diego Silveira; Medeiros, André Macêdo; Macêdo, Priscila Tavares; Leão, Anderson Henrique; Ribeiro, Alessandra Mussi; Izídio, Geison Souza; Silva, Regina Helena

    2016-10-01

    Studies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women.

  11. [Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression].

    PubMed

    Piasecka, Dominika; Składanowski, Andrzej C; Kordek, Radzisław; Romańska, Hanna M; Sądej, Rafał

    2015-01-01

    Progesterone receptor (PR) and its specific ligand play a key role in development and physiology of mammary gland. The role of PR in initiation and progression of breast carcinoma (BCa) is unquestionable, although molecular mechanism of PR action is complex and not fully understood. It is known that increased risk of breast cancer is associated with progestin-based (synthetic ligands of progesterone) hormonal contraception or hormone replacement therapies. It is estimated that ER/PR-positive tumours represent approximately 50-70% of all BCa cases, and the loss of PR is associated with resistance to hormonal therapy and increased tumour invasiveness. In classical, genomic signalling pathway cytoplasmic PR, following ligand binding, translocates to the nucleus and regulates expression of genes with the PRE sequence. PR is also involved in a large number of alternative, non-genomic signalling cascades, e.g. PR is able to activate MAPK and PI3K/AKT pathways, which leads to regulation of gene expression. The cross-talk between PR and Growth Factors Receptors (GFR) results in progesterone-independent activation of PR as well as PR-regulated GFR expression and activation. Growth factors signalling promotes formation of a pool of hypersensitive PR responsive to even very low ligand concentration. Transcriptional activity of PR as well as its dynamic impact on processes such as cell migration and adhesion are crucial for BCa progression. Further studies of multifaceted mechanisms of PR action may contribute to new PR-targeting therapeutic strategies for breast cancer patients. PMID:26689013

  12. Plasma progesterone profile and conception rate following exogenous supplementation of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone releasing intra-vaginal device in repeat-breeder crossbred cows

    PubMed Central

    Pandey, N. K. J.; Gupta, H. P.; Prasad, Shiv; Sheetal, S. K.

    2016-01-01

    Aim: This study was designed to evaluate the effect of gonadotropin-releasing hormone (GnRH), human chorionic gonadotropin (hCG), and progesterone impregnated intra-vaginal device on progesterone profile and conception rate in repeat-breeding crossbred cows. Materials and Methods: Repeat-breeding crossbred cows aged 3-8 years (n=32), lactating and negative to white side test were randomly divided into four groups: Group 1 (Control, n=8), Group 2 (GnRH at 10 µg i.m, n=8), Group 3 (hCG at 1500 IU i.m., n=8), and Group 4 (progesterone impregnated intra-vaginal device at 958 mg, n=8). All the treatme nts were given on 5th daypostbreeding and in Group 4 intra-vaginally implanted device was withdrawn on 9th day (i.e., implant inserted for total 4 days) of the estrous cycle. Blood samples were collected on day 0, 5, 10, 15, and day 20 of estrous cycle, and plasma was separated for progesterone estimation. Results: Accessory corpus luteum was not formed in crossbred cows of Group4 and control group. However, total 6 and 8 accessory corpora lutea were found in Group 2 and Group 3, respectively. In pregnant cows, the plasma progesterone concentration increased continuously from day 0 to day 20. In non-pregnant cows, it increased from day 0 to day 15 and then declined. The conception rate on day 60 in Group 1, Group 2, Group 3, and Group 4 was 37.5%, 50%, 75%, and 37.5%, respectively. Conclusions: Treating repeat-breeder cows with hCG is effective in increasing conception rate by developing accessory corpora lutea and higher progesterone level. PMID:27397976

  13. Factors controlling proliferation and progesterone production by bovine granulosa cells in serum-free medium.

    PubMed

    Savion, N; Lui, G M; Laherty, R; Gospodarowicz, D

    1981-08-01

    Bovine granulosa cells seeded in the presence of serum on extracellular matrix-coated dishes proliferate actively when exposed to serum-free medium supplemented with insulin (2 microgram/ml), fibroblast growth factor (FGF, 100 ng/ml), and high density lipoprotein (HDL, 30 microgram protein/ml). The final density of the cultures is 80-120% that of cultures grown in the presence of medium supplemented with optimal concentration (10%) of calf serum. Insulin has the greatest effect on cell proliferation when added alone to serum-free medium, since it induced an increase in cell number that was 35-60% that observed with optimal serum concentration. Somatomedin C can replace insulin when added alone. FGF, epidermal growth factor, or HDL had no significant effect on cell proliferation by themselves. When these factors were added together with insulin, they acted synergistically in stimulating cell proliferation. When cultures were seeded in the total absence of serum, the addition of transferrin (10 microgram/ml) to serum-free medium was required in order for insulin and FGF to be mitogenic. Cultures maintained on extracellular matrix and exposed to serum-free medium alone have a lifespan in culture of 4 generations. Addition of insulin, FGF, and HDL increases the lifespan of the cultures to 12 generations. Bovine granulosa cells, which proliferate in a defined medium, respond to dibutyryl cAMP by releasing progesterone into the medium. Addition of FSH to the defined medium resulted in a 30% decrease in cell proliferation and in a 2.1-fold increase in the amount of progesterone released into the medium in response to dibutyryl cAMP. This release of progesterone reached a level similar to that observed with cultures grown in medium supplemented with optimal concentration of serum and exposed or not to FSH during their growth phase and at confluence. These results demonstrate that bovine granulosa cells can actively proliferate in a serum-free medium and maintain their

  14. Peripheral plasma levels of progesterone in pregnant goats and in pregnant goats treated with prostaglandin F2a.

    PubMed

    Bosu, W T; Serna Garibay, J A; Barker, C A

    1979-02-01

    Prostaglandin or prostaglandin analogues have been shown to be luteolytic in the pregnant goat. In this study the temporal changes in the plasma concentrations of progesterone during pregnancy and after administration of PGF2a to pregnant goats are described. PGF2a administration to pregnant goats at 30 and 65 days after breeding induced abortion within 34 to 75 hours. These abortions were accompanied by estrus and profuse muco-hemorrhagic discharges. When PGF2a was administered to pregnant goats 140 or 142 days after breeding, premature parturition occurred within 42 to 76 hours. Live kids were delivered in all cases. The plasma levels of progesterone in all pregnant goats showed dramatic decreases within 24 hours after the prostaglandin injections and continued to decrease gradually until abortions or premature parturition. Thereafter, the progesterone levels remained low for several days. PMID:16725398

  15. Occurrence and removal of estrogens, progesterone and testosterone in three constructed wetlands treating municipal sewage in the Czech Republic.

    PubMed

    Vymazal, Jan; Březinová, Tereza; Koželuh, Milan

    2015-12-01

    Estrogenic hormones, progesterone and testosterone are endocrine-disrupting chemicals and their presence in aquatic environments represents a potentially adverse environmental and public health impact. There is a considerable amount of information about removal of estrogens, progesterone and testosterone in conventional wastewater treatment plants, namely activated sludge systems. However, the information about removal of these compounds in constructed wetlands is very limited. Three constructed wetlands with horizontal subsurface flow in the Czech Republic have been selected to evaluate removal of estrogens (estrone, estriol, 17β-estradiol, 17α-ethinylestradiol), testosterone and progesterone. Monitored constructed wetlands for 100, 150 and 200 PE have been in operation for more than 10 years and all systems exhibit very high treatment efficiency for organics and suspended solids. The results indicate that removal of all estrogens, progesterone and testosterone was high and only estrone was found in the outflow from one constructed wetland in concentrations above the limit of quantification 1 ng l(-1). The limits of quantification for other estrogens, i.e., 10 ng l(-1) for estriol, 1 ng l(-1) for 17β-estradiol and 2 ng l(-1) for 17α-ethinylestradiol were not exceeded in the outflow of all monitored constructed wetlands. Also, for progesterone and testosterone, all outflow concentrations were below the LOQ of 0.5 ng l(-1). The results indicated that constructed wetlands with horizontal subsurface flow are a promising technology for elimination of estrogens, progesterone and testosterone from municipal sewage but more information is needed to confirm this finding. PMID:26247691

  16. Validation of a serum immunoassay to measure progesterone and diagnose pregnancy in the West Indian manatee (Trichechus manatus).

    PubMed

    Tripp, K M; Verstegen, J P; Deutsch, C J; Bonde, R K; Rodriguez, M; Morales, B; Schmitt, D L; Harr, K E

    2008-10-15

    The objective was to validate a high-sensitivity chemiluminescent assay of serum progesterone concentrations for pregnancy diagnosis in manatees. Assay analytical sensitivity was 0.1 ng/mL, with mean intra- and inter-assay coefficients of variation of 9.7 and 9.2%, respectively, and accuracy had a mean adjusted R(2) of 0.98. Methods comparison (relative to Siemen's Coat-A-Count RIA) demonstrated r=0.98, Deming regression slope of 0.95, and an intercept of 0.01. Based on ROC analysis, a progesterone concentration >or=0.4 ng/mL was indicative of pregnancy. Assay results were not significantly altered by two freeze-thaw cycles of samples. Characteristic progesterone concentrations during pregnancy were Months 1-4 (1.7-4.7 ng/mL), 5-8 ( approximately 1.0 ng/mL), and 10 and 11 (0.3-0.5 ng/mL), whereas two late-pregnant females with impending abortion had progesterone concentrations of 0.1 ng/mL. Among pregnant females, maximum progesterone concentrations occurred in autumn (3.9+/-1.8 ng/mL), and were greater during all seasons than concentrations in non-pregnant females (0.1-0.2 ng/mL). Progesterone concentrations were also significantly higher in pregnant females than in non-pregnant females and males. This highly sensitive, specific, and diagnostic assay will be valuable for monitoring pregnancy and abortion in manatees.

  17. Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

    PubMed Central

    Kannan, Athilakshmi; Davila, Juanmahel; Zhao, Yuechao; Nowak, Romana A.; Bagchi, Milan K.; Bagchi, Indrani C.; Li, Quanxi

    2016-01-01

    Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis. PMID:27776183

  18. Effect of high progesterone concentrations during the early luteal phase on the length of the ovulatory cycle of goats.

    PubMed

    Menchaca, A; Rubianes, E

    2001-10-31

    The effect of exogenous progesterone exposure early in the oestrous cycle on the duration of the interovulatory interval was studied in dairy goats. A controlled intravaginal drug release (CIDR-G) device was inserted for 5 days starting at day 0 (D0 group, n=6) or day 3 (D3 group, n=5) postovulation. A third group was composed of untreated control goats (control group, n=7). Daily transrectal ultrasound was carried out during the interovulatory interval to assess the ovarian dynamics. Oestrous behaviour was checked twice a day and serum progesterone levels were assayed in daily jugular blood samples. Treated goats showed two different responses. In three D0 goats and one D3 goat, progesterone concentrations fell immediately after CIDR withdrawal and this was followed by oestrus and ovulation between days 8 and 11 (short cycles). In the other three D0 goats and in four D3 goats the treatment significantly reduced the interovulatory interval (18.3+/-0.3 and 18.5+/-0.3 days, respectively) (shortened cycles) compared with the control group (20.0+/-0.2 days; P<0.05), but the intervals with progesterone concentrations over 1 ng/ml were not different (15.7+/-0.3, 15.8+/-0.7 and 16.0+/-0.5 days for D0, D3 and control goats, respectively). In all D0 goats with a short cycle response, the ovulatory follicle arose from the first follicular wave but in the D3 goat with a short cycle it arose from the second follicular wave. These results showed that premature progesterone exposure early in the ovulatory cycle of the goat affected its length inducing short or shortened cycles. The effect of progesterone could either affect luteotropic support of the corpus luteum (CL) and/or stimulate a premature release of the luteolysin. PMID:11600275

  19. Validation of a serum immunoassay to measure progesterone and diagnose pregnancy in the West Indian manatee (Trichechus manatus).

    PubMed

    Tripp, K M; Verstegen, J P; Deutsch, C J; Bonde, R K; Rodriguez, M; Morales, B; Schmitt, D L; Harr, K E

    2008-10-15

    The objective was to validate a high-sensitivity chemiluminescent assay of serum progesterone concentrations for pregnancy diagnosis in manatees. Assay analytical sensitivity was 0.1 ng/mL, with mean intra- and inter-assay coefficients of variation of 9.7 and 9.2%, respectively, and accuracy had a mean adjusted R(2) of 0.98. Methods comparison (relative to Siemen's Coat-A-Count RIA) demonstrated r=0.98, Deming regression slope of 0.95, and an intercept of 0.01. Based on ROC analysis, a progesterone concentration >or=0.4 ng/mL was indicative of pregnancy. Assay results were not significantly altered by two freeze-thaw cycles of samples. Characteristic progesterone concentrations during pregnancy were Months 1-4 (1.7-4.7 ng/mL), 5-8 ( approximately 1.0 ng/mL), and 10 and 11 (0.3-0.5 ng/mL), whereas two late-pregnant females with impending abortion had progesterone concentrations of 0.1 ng/mL. Among pregnant females, maximum progesterone concentrations occurred in autumn (3.9+/-1.8 ng/mL), and were greater during all seasons than concentrations in non-pregnant females (0.1-0.2 ng/mL). Progesterone concentrations were also significantly higher in pregnant females than in non-pregnant females and males. This highly sensitive, specific, and diagnostic assay will be valuable for monitoring pregnancy and abortion in manatees. PMID:18760463

  20. Occurrence and removal of estrogens, progesterone and testosterone in three constructed wetlands treating municipal sewage in the Czech Republic.

    PubMed

    Vymazal, Jan; Březinová, Tereza; Koželuh, Milan

    2015-12-01

    Estrogenic hormones, progesterone and testosterone are endocrine-disrupting chemicals and their presence in aquatic environments represents a potentially adverse environmental and public health impact. There is a considerable amount of information about removal of estrogens, progesterone and testosterone in conventional wastewater treatment plants, namely activated sludge systems. However, the information about removal of these compounds in constructed wetlands is very limited. Three constructed wetlands with horizontal subsurface flow in the Czech Republic have been selected to evaluate removal of estrogens (estrone, estriol, 17β-estradiol, 17α-ethinylestradiol), testosterone and progesterone. Monitored constructed wetlands for 100, 150 and 200 PE have been in operation for more than 10 years and all systems exhibit very high treatment efficiency for organics and suspended solids. The results indicate that removal of all estrogens, progesterone and testosterone was high and only estrone was found in the outflow from one constructed wetland in concentrations above the limit of quantification 1 ng l(-1). The limits of quantification for other estrogens, i.e., 10 ng l(-1) for estriol, 1 ng l(-1) for 17β-estradiol and 2 ng l(-1) for 17α-ethinylestradiol were not exceeded in the outflow of all monitored constructed wetlands. Also, for progesterone and testosterone, all outflow concentrations were below the LOQ of 0.5 ng l(-1). The results indicated that constructed wetlands with horizontal subsurface flow are a promising technology for elimination of estrogens, progesterone and testosterone from municipal sewage but more information is needed to confirm this finding.