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Sample records for follicular stimulating hormone

  1. Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone.

    PubMed

    Messinis, I E; Milingos, S; Zikopoulos, K; Kollios, G; Seferiadis, K; Lolis, D

    1998-05-01

    It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women. PMID:9647537

  2. Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

    PubMed Central

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

    A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

  3. Follicular characteristics and luteal development after follicle-stimulating hormone induced multiple ovulations in heifers.

    PubMed

    Glick, G; Hogeg, M; Moallem, U; Lavon, Y; Wolfenson, D

    2013-01-01

    A protocol based on small doses of FSH was examined for the induction of double or triple (multiple) ovulations in cattle. Ovulation rate, follicular characteristics, and luteal responses were determined. In Exp. 1, three groups of estrous-synchronized, cyclic Holstein heifers were treated once daily, on d 3 to 6 of the cycle, with a FSH product (Folltropin-V): large FSH dose (total of 150 mg; n=18), medium FSH dose (total of 130 mg, n=12), and small FSH dose (total of 80 mg; n=7). Controls received saline (n=6). Prostaglandin F(2α) was injected on d 6, ultrasound-guided aspiration of surplus follicles (if needed) was performed on d 7, and GnRH was injected on d 8 to induce ovulation. The large FSH dose induced growth of more (2.6±0.3, P<0.05) large follicles than controls on d 8; medium and small FSH doses insufficiently stimulated growth of <2 large follicles. Ovulation rates were determined in subgroups of heifers (n=10, 13, 4, and 6, respectively). The large FSH dose induced greater rates (P<0.01) of mostly double and triple ovulations (90% multiple ovulations, 70% double ovulations), most of which (89%) were bilateral, with only 2 out of 10 heifers requiring aspiration of surplus follicles. Medium and small FSH doses induced fewer multiple ovulations (38% and 25%, respectively). Estradiol concentrations on d 8 did not differ among treatments, but the concentration per large follicle in controls was greater (P<0.05) than in FSH treatments. Mean corpus luteum (CL) volume in single-ovulation controls was greater (P<0.05) than that of multiple ovulations in the large FSH group and total CL volume and progesterone concentrations were numerically greater in multiple ovulations. In Exp. 2, the characteristics of follicles aspirated on d 7 from large FSH (n=11) and control heifers (n=10) were compared. Based on estradiol-to-progesterone ratio, 57% of the large FSH-treated follicles were classified as codominant/healthy follicles and 43% as subordinate/early atretic

  4. Serum copper, follicular stimulating hormone, luteinizing hormone, prolactin, spermatic count, viability, progression and seminal zinc correlations in a human (male) infertility study

    SciTech Connect

    Sella, G.E.; Cunnane, S.C.; McInnes, R.A.

    1981-06-01

    The role of copper and its correlations to other parameters has been investigated in a male-fertility pilot study at a University infertility clinic in Montreal. Serum and semen Cu concentrations were determined in 100 men (age 25 to 54 years) referred to the clinic for infertility evaluation. The results of the significant correlations between serum Cu concentrations and male fertility parameters such as (1) the serum concentrations of the hormones FSH, LH and prolactin; (2) spermatozoal count, viability and progression and (3) seminal zinc concentrations are reported.

  5. Intracellular mechanism of the action of inhibin on the secretion of follicular stimulating hormone and of luteinizing hormone induced by LH-RH in vitro

    NASA Technical Reports Server (NTRS)

    Lecomte-Yerna, M. J.; Hazee-Hagelstein, M. T.; Charlet-Renard, C.; Franchimont, P.

    1982-01-01

    The FSH secretion-inhibiting action of inhibin in vitro under basal conditions and also in the presence of LH-RH is suppressed by the addition of MIX, a phosphodiesterase inhibitor. In the presence of LH-RH, inhibin reduces significantly the intracellular level of cAMP in isolated pituitary cells. In contrast, the simultaneous addition of MIX and inhibin raises the cAMP level, and this stimulation is comparable to the increase observed when MIX is added alone. These observations suggest that one mode of action of inhibin could be mediated by a reduction in cAMP within the pituitary gonadotropic cell.

  6. Increased food intake stimulates GnRH-I, glycoprotein hormone alpha-subunit and follistatin mRNAs, and ovarian follicular numbers in laying broiler breeder hens.

    PubMed

    Ciccone, N A; Dunn, I C; Sharp, P J

    2007-07-01

    The aim of this study, in 36 week-old laying broiler breeder hens, was to establish the effects on reproductive neuroendocrine gene expression of reinstating ad libitum food intake after moderate food restriction from 2 weeks of age. Seven days of ad libitum feeding increased the number of large pre-ovulatory ovarian follicles and gonadotropin releasing hormone-I (GnRH-I), glycoprotein hormone alpha-subunit and follistatin mRNAs. Plasma luteinizing hormone (LH) was also increased while plasma follicle-stimulating hormone (FSH) was reduced. There were no associated changes in gonadotropin inhibitory hormone (GnIH), LHbeta or FSHbeta mRNAs. The mechanism underlying the increased expression of alpha-subunit and follistatin mRNAs was investigated in vitro by incubating pituitary fragments with pulses of GnRH-I. This treatment increased alpha-subunit and follistatin mRNAs but did not affect gonadotropin beta-subunit mRNAs. It is concluded that lifting food restriction in laying hens increases GnRH-I gene transcription or mRNA stability which may be a consequence, or cause of increased GnRH-I release. This, in turn, increases glycoprotein hormone alpha-subunit and follistatin mRNAs, resulting in increased plasma LH and decreased plasma FSH, respectively. PMID:16737793

  7. Growth hormone stimulation test

    MedlinePlus

    The growth hormone (GH) stimulation test measures the ability of the body to produce GH. ... killing medicine (antiseptic). The first sample is drawn early in the morning. Medicine is given through the ...

  8. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    PubMed

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  9. Do analogues of gonadotrophin releasing hormone influence follicular fluid steroid levels, oocyte maturity and fertilization rates?

    PubMed

    Tavmergen, E; Tavmergen, E N; Capanoğlu, R

    1992-04-01

    One-hundred-and-twelve samples of follicular fluid from 32 patients undergoing in-vitro fertilization and embryo transfer were analysed in this study. The follicular fluids were analysed for any relationships between oestradiol, progesterone and 17 alpha-hydroxyprogesterone levels, the progesterone/oestradiol and 17 alpha-hydroxyprogesterone/oestradiol ratios and oocyte maturity and fertilization rates. In Group A, consisting of women who used analogues of gonadotrophin-releasing hormone during ovarian stimulation with human menopausal gonadotrophin, the progesterone/oestradiol ratio rose in parallel with the fertilization rate (P less than 0.05). Group B comprised patients treated with human menopausal gonadotrophin alone. No significant relationship was found between the other parameters, oocyte maturation and fertilization rates in either group. PMID:1387881

  10. Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation

    PubMed Central

    Raju, Gottumukkala Achyuta Rama; Chavan, Rahul; Deenadayal, Mamata; Gunasheela, Devika; Gutgutia, Rohit; Haripriya, Geetha; Govindarajan, Mirudhubashini; Patel, Nayana Hitesh; Patki, Ameet Shashikant

    2013-01-01

    Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART. PMID:24672160

  11. Gonadotropin-releasing hormone treatment induces follicular growth and ovulation in seasonally anestrous mares.

    PubMed

    Johnson, A L

    1987-06-01

    A study was conducted to evaluate the effectiveness of gonadotropin-releasing hormone (GnRH) pulse infusion to stimulate follicular development and induce ovulation in seasonally anestrous standardbred mares. Seventeen mares were selected for use in this experiment, on the basis of a previous normal reproductive history, and were housed under a photoperiod of 8L:16D beginning one week prior to the start of the experiment (second week in January). Mares were infused with 20 micrograms (n = 7) or 2 micrograms (n = 6) GnRH/h, or were subjected to photoperiod treatment only (controls, n = 4). Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone did not vary, and neither significant follicular development nor ovulation was observed in any control mare throughout the experimental period (greater than 60 days). By contrast, both groups of GnRH-treated mares showed elevated serum concentrations of LH and FSH within one day after the start of infusion. Mares infused with 20 micrograms GnRH/h had at least one follicle greater than or equal to 25 mm in 7.4 +/- 1.3 (mean +/- SEM) days following the start of infusion, and ovulated in 12.0 +/- 0.7 days. In the 2-microgram-GnRH/h treatment group, a 25-mm follicle was detected in 5.7 +/- 0.7 days, and ovulation occurred after 10.0 +/- 0.3 days of infusion. Ovulation in every instance was followed by a functional luteal phase, as indicated by the profiles of progesterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3113502

  12. Follicle-stimulating Hormone Activation of Hypoxia-inducible Factor-1 by the Phosphatidylinositol 3-Kinase/AKT/Ras Homolog Enriched in Brain (Rheb)/Mammalian Target of Rapamycin (mTOR) Pathway Is Necessary for Induction of Select Protein Markers of Follicular Differentiation*

    PubMed Central

    Alam, Hena; Maizels, Evelyn T.; Park, Youngkyu; Ghaey, Shail; Feiger, Zachary J.; Chandel, Navdeep S.; Hunzicker-Dunn, Mary

    2006-01-01

    We sought to elucidate the role of AKT in follicle-stimulating hormone (FSH)-mediated granulosa cell (GC) differentiation. Our results define a signaling pathway in GCs whereby the inactivating phosphorylation of tuberin downstream of phosphatidylinositol (PI) 3-kinase/AKT activity leads to Rheb (Ras homolog enriched in brain) and subsequent mTOR (mammalian target of rapamycin) activation. mTOR then stimulates translation by phosphorylating p70 S6 kinase and, consequently, the 40 S ribosomal protein S6. Activation of this pathway is required for FSH-mediated induction of several follicular differentiation markers, including luteinizing-hormone receptor (LHR), inhibin-α, microtubule-associated protein 2D, and the PKA type IIβ regulatory subunit. FSH also promotes activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). FSH-stimulated HIF-1 activity is inhibited by the PI 3-kinase inhibitor LY294002, the Rheb inhibitor FTI-277 (farne-syltransferase inhibitor-277), and the mTOR inhibitor rapamycin. Finally, we find that the FSH-mediated up-regulation of reporter activities for LHR, inhibin-α, and vascular endothelial growth factor is dependent upon HIF-1 activity, because a dominant negative form of HIF-1α interferes with the up-regulation of these genes. These results show that FSH enhances HIF-1 activity downstream of the PI 3-kinase/AKT/Rheb/mTOR pathway in GCs and that HIF-1 activity is necessary for FSH to induce multiple follicular differentiation markers. PMID:14982927

  13. The relationship between serum anti-Müllerian hormone levels and the follicular arrest for women with polycystic ovary syndrome.

    PubMed

    Li, Jian; Li, Rong; Yu, Hua; Zhao, Shuyun; Yu, Yang; Qiao, Jie

    2015-04-01

    The aim of this study was to ascertain whether higher levels of serum anti-Müllerian hormone (AMH) are associated with the ovarian follicular arrest in women with polycystic ovary syndrome (PCOS). This prospective study compared AMH levels between serum and dominant follicular fluid (FF) in ovulatory polycystic ovary (PCO) women and anovulatory (menstrual cycle ≥60 days.) PCOS women. All 102 women provided a baseline hormone profile and underwent controlled ovarian hyperstimulation (COH). The anovulatory PCO women had a similar body mass index (BMI), antral follicle count (AFC), and baseline serum AMH levels as the ovulatory PCO women except that their median luteinizing hormone (LH; 10.0 mIU/ml), testosterone (T) (0.61 ng/l), and androstenedione (A) (3.47 ng/l) levels were significantly higher than ovulatory PCO women (4.9 mIU/m; 0.43 ng/l and 2.09 ng/l, respectively). The ovarian response to gonadotropin stimulation during COH including serum AMH on the day of HCG administration and dominant FF AMH at 36 hours after HCG administration, total follicle stimulating hormone (FSH) dose administrated, peak E2, (estrogen) levels and number of occytes retrieved were all similar between women with anovulatory and ovulatory PCO. Using multiple regression analysis it was found that an important independent determinant affecting AMH was AFC, as opposed to LH and T. Logistic regression analysis showed that the two most important factors affecting ovulation were serum LH and T, whereas serum AMH and AFC were not selected for inclusion in the model. The reduction in AMH during COH occurs as a consequence of dominant follicles with a corresponding reduction in small antral follicle number. Elevated serum AMH levels in PCO women seem to be related only to follicular excess and not follicular arrest. PMID:25329139

  14. The Role of Androgen Hormones in Early Follicular Development

    PubMed Central

    Gervásio, Catiele Garcia; Bernuci, Marcelo Picinin; Silva-de-Sá, Marcos Felipe; Rosa-e-Silva, Ana Carolina Japur de Sá

    2014-01-01

    Background. Although chronic hyperandrogenism, a typical feature of polycystic ovary syndrome, is often associated with disturbed reproductive performance, androgens have been shown to promote ovarian follicle growth in shorter exposures. Here, we review the main effects of androgens on the regulation of early folliculogenesis and the potential of their application in improving follicular in vitro growth. Review. Androgens may affect folliculogenesis directly via androgen receptors (ARs) or indirectly through aromatization to estrogen. ARs are highly expressed in the granulosa and theca cells of early stage follicles and slightly expressed in mature follicles. Short-term androgen exposure augments FSH receptor expression in the granulosa cells of developing follicles and enhances the FSH-induced cAMP formation necessary for the transcription of genes involved in the control of follicular cell proliferation and differentiation. AR activation also increases insulin-like growth factor (IGF-1) and its receptor gene expression in the granulosa and theca cells of growing follicles and in the oocytes of primordial follicles, thus facilitating IGF-1 actions in both follicular recruitment and subsequent development. Conclusion. During the early and intermediate stages of follicular maturation, locally produced androgens facilitate the transition of follicles from the dormant to the growing pool as well as their further development. PMID:25006485

  15. Neural correlates of erotic stimulation under different levels of female sexual hormones.

    PubMed

    Abler, Birgit; Kumpfmüller, Daniela; Grön, Georg; Walter, Martin; Stingl, Julia; Seeringer, Angela

    2013-01-01

    Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results

  16. Gonadotropin stimulation regimens for follicular aspiration and in vitro embryo production from calf oocytes.

    PubMed

    Armstrong, D T; Irvine, B J; Earl, C R; McLean, D; Seamark, R F

    1994-01-01

    Crossbred beef x dairy calves were randomly allocated at 3 wk of age to different gonadotropin treatment regimens for stimulation of follicle development and induction of oocyte maturation in vivo. Follicular responses were assessed laparoscopically, and oocytes were aspirated for assessment of maturational state or for in vitro fertilization (IVF) and culture to determine developmental capacity. Follicle-stimulating Hormone (FSH), administered in a single subcutaneous injection together with a low dosage of PMSG, was as effective as the same total dosage of FSH administered in 6 injections over a 3-d period. Without accompanying PMSG, this dose of FSH was ineffective in stimulating follicle development. The mean number of preovulatory follicles (> 5mm, with hyperemic appearance) doubled with each successive stimulation at 3-wk intervals, reaching 35 follicles per calf at 9 wk of age. Oocyte yields ranged from 55 to 81% of follicles aspirated, and did not differ significantly among age, FSH regimen and oocyte maturation stimulus. A combination of LH + FSH was more effective in stimulating cumulus cell expansion than LH by itself (73 vs 22% of recovered oocyte-cumulus cell complex (OCC) respectively; P<0.05). Of 33 unselected immature oocytes (cumulus unexpanded) subjected to in vitro maturation (IVM) and IVF, 30% developed to blastocysts during co-culture with bovine oviduct epithelial cells, which was not significantly different from 25% of 36 oocytes from adult ovaries which reached the blastocyst stage under similar conditions. The results indicate that follicle responses of calf ovaries to FSH stimulation increase progressively from 3 to 9 wk of age, and that oocytes recovered laparoscopically from these follicles produce blastocysts in culture at rates similar to oocytes from adult cattle ovaries collected at slaughter. The approach offers promise for embryo production from donor calves of superior genetic merit for embryo transfer, thereby enhancing the rate

  17. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B.

    1987-07-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse.

  18. Growth hormone stimulation test (image)

    MedlinePlus

    ... test is performed by administering the amino acid arginine in a vein to raise hGH levels. The ... to secrete growth hormone in response to the arginine. Lack of hGH can cause growth retardation in ...

  19. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  20. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  1. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  2. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  3. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  4. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats.

    PubMed

    Fedail, Jaafar Sulieman; Zheng, Kaizhi; Wei, Quanwei; Kong, Lingfa; Shi, Fangxiong

    2014-08-01

    Thyroid hormones (TH) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. However, whether TH can affect ovarian follicular development in neonatal and immature rats remains unclear. Therefore, the aim of the present study was to elucidate the effect of TH on ovarian follicular development in neonatal and immature rats. Thirty female post-lactation mothers of Sprague-Dawley rat pups were randomly divided into three groups: control, hyperthyroid (hyper), and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRα1) and nitric oxide synthase types (NOS), and NOS activities, were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P < 0.05). In addition, the hyper group had increased serum concentrations of T3, T4, and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4, and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P < 0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND 21 compared with the control group (P < 0.05). Immunostaining indicated that TRα1 and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, with strong staining of the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND 10 and 21. In summary, our findings suggest that TH play important roles in ovarian functions and in the regulation of NOS activity. Our results also indicate that a relationship exists between the TH and NO signaling pathways during the process of ovarian follicular

  5. Intra-cellular mechanism of Anti-Müllerian hormone (AMH) in regulation of follicular development.

    PubMed

    Hayes, Emily; Kushnir, Vitaly; Ma, Xiaoting; Biswas, Anindita; Prizant, Hen; Gleicher, Norbert; Sen, Aritro

    2016-09-15

    Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily and plays a crucial role in testicular and ovarian functions. In clinical practice, AMH is used as a diagnostic and/or prognostic marker in women in association with ovulation induction and in various pathophysiological conditions. Despite widespread clinical use of AMH, our mechanistic understanding of AMH actions in regulating follicular development is limited. Using a mouse model, we in this study report that in vivo AMH treatment while stalls follicular development and inhibits ovulation, also prevents follicular atresia. We further show that these AMH actions are mediated through induction of two miRNAs, miR-181a and miR-181b, which regulate various aspects of FSH signaling and follicular growth, ultimately affecting downstream gene expression and folliculogenesis. We also report that in this mouse model AMH pre-treatment prior to superovulation improves oocyte yield. These studies, therefore, offer new mechanistic insight into AMH actions in folliculogenesis and point toward potential utilization of AMH as a therapeutic agent. PMID:27235859

  6. Gonadotropin-inhibitory hormone (GnIH) receptor gene is expressed in the chicken ovary: potential role of GnIH in follicular maturation.

    PubMed

    Maddineni, Sreenivasa R; Ocón-Grove, Olga M; Krzysik-Walker, Susan M; Hendricks, Gilbert L; Ramachandran, Ramesh

    2008-02-01

    Gonadotropin-inhibitory hormone (GnIH), an RFamide peptide, has been found to inhibit pituitary LH secretion in avian and mammalian species. The gene encoding a putative receptor for GnIH (GnIHR) was recently identified in the chicken and Japanese quail brain and pituitary gland. GnIHR appears to be a seven-transmembrane protein belonging to a family of G-protein-coupled receptors. In the present study, we have characterized the expression of GnIHR mRNA in the chicken ovary and demonstrate that GnIHR may exert an inhibitory effect on ovarian follicular development. By RT-PCR, we detected GnIHR mRNA in the chicken testis and in the ovary, specifically both thecal and granulosa cell layers. Real-time quantitative PCR analysis revealed greater GnIHR mRNA quantity in theca cells of prehierarchial follicles compared with that of preovulatory follicles. GnIHR mRNA quantity was significantly decreased in sexually mature chicken ovaries versus ovaries of sexually immature chickens. Estradiol (E(2)) and/or progesterone (P(4)) treatment of sexually immature chickens significantly decreased ovarian GnIHR mRNA abundance. Treatment of prehierarchial follicular granulosa cells in vitro with chicken GnIH peptide significantly decreased basal but not FSH-stimulated cellular viability. Collectively, our results indicate that the ovarian GnIHR is likely to be involved in ovarian follicular development. A decrease in ovarian GnIHR mRNA abundance due to sexual maturation or by E(2) and/or P(4) treatment would implicate an inhibitory role for GnIHR in ovarian follicular development. Furthermore, GnIH may affect follicular maturation by decreasing the viability of prehierarchial follicular granulosa cells through binding to GnIHR. PMID:18239054

  7. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.

    PubMed

    Haughian, James M; Ginther, O J; Diaz, Francisco J; Wiltbank, Milo C

    2013-06-01

    Mechanisms regulating gonadotropin surges and gonadotropin requirements for follicle emergence and selection were studied in heifers. Experiment 1 evaluated whether follicular inhibins regulate the preovulatory luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surges elicited by gonadotropin-releasing hormone (GnRH) injection (Hour = 0) and the subsequent periovulatory FSH surge. Treatments included control (n = 6), steroid-depleted bovine follicular fluid (bFF) at Hour -4 (n = 6), and bFF at Hour 6 (n = 6). Gonadotropins in blood were assessed hourly from Hours -6 to 36, and follicle growth tracked by ultrasound. Consistent with inhibin independence, bFF at Hour -4 did not impact the GnRH-induced preovulatory FSH surge, whereas treatment at Hour 6 delayed onset of the periovulatory FSH surge and impeded growth of a new follicular wave. Experiment 2 examined GnRH and estradiol (E2) regulation of the periovulatory FSH surge. Treatment groups were control (n = 8), GnRH-receptor antagonist (GnRHr-ant, n = 8), and E2 + GnRHr-ant (n = 4). GnRHr-ant (acyline) did not reduce the concentrations of FSH during the periovulatory surge and early follicle development (<7.0 mm) was unaffected, although subsequent growth of a dominant follicle (>8.0 mm) was prevented by GnRHr-ant. Addition of E2 delayed both the onset of the periovulatory FSH surge and emergence of a follicular wave. Failure to select a dominant follicle in the GnRHr-ant group was associated with reduced concentrations of LH but not FSH. Maximum diameter of F1 in controls (13.3 ± 0.5 mm) was greater than in both GnRHr-ant (7.7 ± 0.3 mm) and E2 + GnRHr-ant (6.7 ± 0.8 mm) groups. Results indicated that the periovulatory FSH surge stems from removal of negative stimuli (follicular E2 and inhibin), but is independent of GnRH stimulation. Emergence and early growth of follicles (until about 8 mm) requires the periovulatory FSH surge but not LH pulses. However, follicular deviation and late-stage growth of

  8. 21 CFR 522.1002 - Follicle stimulating hormone.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Follicle stimulating hormone. 522.1002 Section 522....1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial... hormone. The other vial contains 10 milliliters of aqueous diluent. (2) Sponsor. See No. 052923 in §...

  9. 21 CFR 522.1002 - Follicle stimulating hormone.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Follicle stimulating hormone. 522.1002 Section 522....1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial... hormone. The other vial contains 10 milliliters of aqueous diluent. (2) Sponsor. See No. 052923 in §...

  10. 21 CFR 522.1002 - Follicle stimulating hormone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Follicle stimulating hormone. 522.1002 Section 522....1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial... hormone. The other vial contains 10 milliliters of aqueous diluent. (2) Sponsor. See No. 052923 in §...

  11. 21 CFR 522.1002 - Follicle stimulating hormone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Follicle stimulating hormone. 522.1002 Section 522....1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial... hormone. The other vial contains 10 milliliters of aqueous diluent. (2) Sponsor. See No. 052923 in §...

  12. 21 CFR 522.1002 - Follicle stimulating hormone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Follicle stimulating hormone. 522.1002 Section 522....1002 Follicle stimulating hormone. (a)(1) Specifications. Each package contains 2 vials. One vial... hormone. The other vial contains 10 milliliters of aqueous diluent. (2) Sponsor. See 059521 in §...

  13. Goose broodiness is involved in granulosa cell autophagy and homeostatic imbalance of follicular hormones.

    PubMed

    Yu, Jing; Lou, Yaping; He, Ke; Yang, Songbai; Yu, Wensai; Han, Lu; Zhao, Ayong

    2016-05-01

    Broodiness is observed in most domestic fowls and influences egg production. The goose is one of the most important waterfowls, having strong broody behavior. However, whether autophagy and follicular internal environment play a role in the broodiness behavior of goose is unknown. In this report, we analyzed the follicular internal environment and granulosa cell autophagy of goose follicles. The results show that the contents of hormones, including prolactin (PRL), progesterone (P4), and estradiol (E2), increased in broody goose follicles. Most importantly, the level of granulosa cell autophagy in broody goose follicles was elevated, detected by electron microscopy and western blotting. Also, the expressions of positive regulators of autophagy, including miR-7, miR-29, miR-100, miR-181, PRLR, LC3, p53,Beclin1, Atg9, and Atg12, were up-regulated and the expressions of negative regulators of autophagy, including miR-34b and miR-34c, were down-regulated in broody goose follicles. Our results suggest that goose broodiness is involved in increased granulosa cell autophagy and homeostasis imbalance of internal environment in the follicles. This work contributes to our knowledge of goose broodiness and may influence egg production. PMID:26908882

  14. Intrinsic determinants and predictors of superovulatory yields in sheep: Circulating concentrations of reproductive hormones, ovarian status, and antral follicular blood flow.

    PubMed

    Bartlewski, Pawel M; Seaton, Patricia; Franco Oliveira, Maria Emilia; Kridli, Rami T; Murawski, Maciej; Schwarz, Tomasz

    2016-07-01

    Hormonal ovarian superstimulation has contributed to small ruminant reproduction around the world, impacting genetic improvement and zoosanitary programs, contributing to the conservation of endangered species, and supporting other related biotechnologies. Advanced knowledge surrounding the superovulatory treatments in sheep has resulted in enhanced control of influencing factors and improved the protocols currently used. However, in spite of minimization of some adverse factors, superovulatory responses in ewes still remain variable, preventing the more widespread use of superovulation in commercial embryo transfer programs and reproductive research in this species. Recent evidence demonstrates that changes in antral follicular populations and blood supply, and circulating concentrations of certain reproductive hormones determined at the specific time points just before or during the superovulatory treatment are associated with superovulation success in ewes. This review attempts to compile the data from available literature to identify ovarian and hormonal determinants of the superovulatory outcome in ewes, which can be used to substantially improve the existing protocols and to reduce the extra cost and unnecessary stress imposed on poorly responding animals. An overview of most commonly used and some recently developed, FSH-based ovarian stimulation protocols is given at the outset to highlight variation in the frequency and timing of gonadotropin injections, estrus synchronization methods, and follicular wave synchronization and/or ovulation induction techniques during the superovulatory treatments in ewes. PMID:27173957

  15. Genetic merit for fertility traits in Holstein cows: II. Ovarian follicular and corpus luteum dynamics, reproductive hormones, and estrus behavior.

    PubMed

    Cummins, S B; Lonergan, P; Evans, A C O; Butler, S T

    2012-07-01

    The objective of this study was to characterize the estrous cycle of cows with similar proportions of Holstein genetics, similar genetic merit for milk production traits, but with good (Fert+) or poor (Fert-) genetic merit for fertility traits. In total, 37 lactating cows were enrolled on a protocol to synchronize estrus. Nineteen Fert+ and 12 Fert- cows that successfully ovulated a dominant follicle and established a corpus luteum underwent daily transrectal ultrasonography. Blood sampling was carried out at 8-h intervals from d 0 to 6 and from d 15 to ovulation, and once daily from d 7 to 15. Blood samples were analyzed for progesterone, estradiol, follicle stimulating hormone, and luteinizing hormone. Estrus behavior was recorded using neck activity collars and mounting pads. The Fert+ cows tended to have fewer follicular waves (2.2 vs. 2.7) and had a shorter estrous cycle (21.0 vs. 25.1 d) than Fert- cows. We observed no effect of genotype on day of first-wave emergence or day of first-wave dominant follicle peak diameter, but the peak diameter of the first-wave dominant follicle tended to be larger in Fert- cows. During the first 13 d of the cycle, Fert+ cows developed a corpus luteum that was 16% larger than that in Fert- cows. Circulating progesterone concentrations were 34% greater in Fert+ than in Fert- cows (5.15 vs. 3.84ng/mL, respectively) from d 5 to 13. During the final follicular wave, the interval from preovulatory follicle emergence to ovulation and the interval from preovulatory follicle dominance to ovulation were similar in both genotypes. Maximum preovulatory follicle diameter was larger in Fert+ than Fert- cows (17.9 vs. 16.8mm, respectively); however, circulating concentrations of estradiol were not different between genotypes. A greater proportion of Fert- cows ovulated to a silent heat than Fert+ cows (22 vs. 2%, respectively). Of cows that showed behavioral estrus, Fert+ cows had 41% greater mean activity count; however, no difference was

  16. Early follicular testosterone level predicts preference for masculinity in male faces - but not for women taking hormonal contraception.

    PubMed

    Bobst, Cora; Sauter, Sabine; Foppa, Andrina; Lobmaier, Janek S

    2014-03-01

    It has been shown that women's preference for masculinity in male faces changes across the menstrual cycle. Preference for masculinity is stronger when conception probability is high than when it is low. These findings have been linked to cyclic fluctuations of hormone levels. The purpose of the present study is to further investigate the link between gonadal steroids (i.e. testosterone, estradiol, and progesterone) and masculinity preference in women, while holding the cycle phase constant. Sixty-two female participants were tested in their early follicular cycle phase, when conception probability is low. Participants were shown face pairs and where asked to choose the more attractive face. Face pairs consisted of a masculinized and feminized version of the same face. For naturally cycling women we found a positive relationship between saliva testosterone levels and masculinity preference, but there was no link between any hormones and masculinity preference for women taking hormonal contraception. We conclude that in naturally cycling women early follicular testosterone levels are associated with masculinity preference. However, these hormonal links were not found for women with artificially modified hormonal levels, that is, for women taking hormonal contraception. PMID:24495615

  17. Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study.

    PubMed

    Bersinger, N A; Kollmann, Z; Von Wolff, M

    2014-12-01

    Throughout follicular growth the number of immune cells increases, enhanced under stimulation with exogenous gonadotropins. This treatment, however, may adversely influence folliculogenesis and negatively affect oocyte quality through modifications in the follicular concentrations of cytokines released by these immune cells. We studied this hypothesis by systematically analysing the concentrations of cytokines present in the serum and follicular fluid at the time of follicular aspiration in conventional gonadotropin-stimulated (c-IVF) cycles in comparison with natural cycle IVF (NC-IVF) in which the follicles were naturally matured. Our study involved 37 NC-IVF and 39 c-IVF cycles including 13 women who underwent both therapies. Mean age was 35.3 ± 4.6 (SD) and 34.2 ± 3.7 years in the NC-IVF and c-IVF groups (ns). Thirteen cytokines were determined in matched serum and FF samples. Interleukin (IL)-4, TNF-α, RANTES, eotaxin and interferon-gamma-induced protein-10 concentrations were lower in FF than in serum. IL-6, -8, -10, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median levels in FF than in serum, indicating possible ovarian production. Most of these markers were also increased in concentration in the stimulated (c-IVF) than in the NC groups in the serum, but not in the follicular fluid. This finding can be attributed to the increased number of active follicles present after controlled ovarian stimulation. IL-8 was reduced in c-IVF cycles. Our study did not reveal differences in follicular fluid but in serum cytokine concentrations, suggesting that the follicular immune system might not be significantly affected by gonadotropin stimulation. PMID:25103590

  18. Intrafollicular steroids and anti-mullerian hormone during normal and cystic ovarian follicular development in the cow.

    PubMed

    Monniaux, Danielle; Clemente, Nathalie di; Touzé, Jean-Luc; Belville, Corinne; Rico, Charlène; Bontoux, Martine; Picard, Jean-Yves; Fabre, Stéphane

    2008-08-01

    Development of follicular cysts is a frequent ovarian dysfunction in cattle. Functional changes that precede cyst formation are unknown, but a role for anti-Müllerian hormone (AMH) in the development of follicular cysts has been suggested in humans. This study aimed to characterize intrafollicular steroids and AMH during follicular growth in a strain of beef cows exhibiting a high incidence of occurrence of follicular cysts. Normal follicular growth and cyst development were assessed by ovarian ultrasonography scanning during the 8 days before slaughtering. Experimental regression of cysts was followed by rapid growth of follicles that reached the size of cysts within 3-5 days. These young cysts exhibited higher intrafollicular concentrations of testosterone, estradiol-17beta, and progesterone than large early dominant follicles did in normal ovaries, but they exhibited similar concentrations of AMH. Later-stage cysts were characterized by hypertrophy of theca interna cells, high intrafollicular progesterone concentration, and high steroidogenic acute regulatory protein mRNA expression in granulosa cells. Progesterone and AMH concentrations in the largest follicles (> or =10 mm) and cysts were negatively correlated (r = -0.45, P < 0.01). Smaller follicles (<10 mm) exhibited higher intrafollicular testosterone and estradiol-17beta concentrations in ovaries with cysts compared to normal ovaries. During follicular growth, AMH concentration dropped in follicles larger than 5 mm in diameter and in a similar way in ovaries with and without cysts. In conclusion, enhanced growth and steroidogenesis in antral follicles <10 mm preceded cyst formation in cow ovaries. Intrafollicular AMH was not a marker of cystic development in the cow, but low AMH concentrations in cysts were associated with luteinization. PMID:18448844

  19. Serum hormone concentrations and ovarian follicular wave emergence in Jilin sika deer (Cervus nippon hortulorum) after synchronization of estrous cycles.

    PubMed

    Chen, X M; Wei, H J; Yang, Y F; Xue, H L; Zhao, W G; Zhao, M

    2015-02-01

    The study was conducted to investigate the serum hormone concentrations and follicular dynamics present after synchronous treatment (CIDR) in female Jilin sika deer (n = 15) of estrous cycles. Blood samples were collected to analyze the FSH, LH, estradiol and progesterone during the estrous cycles. Manual transrectal ultrasonography examination was conducted at least thrice weekly to monitor the follicular wave. Ultrasonography showed that follicle development occurred in waves, and most estrous cycles in Jilin sika deer consist of one, two, or three waves. The largest follicles of the interwaves of two- and three-wave cycles were different (P < 0.05). The mean interovulatory interval was 15.0 ± 4.6 d. There was a surge in circulating FSH in two- and three-wave cycles. The emergence of the largest follicle was related to the peak of serum concentration of estradiol. Serum progesterone concentrations were not different between one- and three-wave cycles (P < 0.05). We concluded that FSH and estradiol concentration may have an important role in controlling follicular development, that the estrous cycle in Jilin sika deer is characterized by one, two, or three waves of follicular development after synchronization. PMID:25563157

  20. Effects of GnRH agonists on the expression of developmental follicular anti-mullerian hormone in varying follicular stages in cyclic mice in vivo

    PubMed Central

    HUANG, JILIANG; WANG, XIAOYAN; LI, ZHILING; MA, RUOWU; XIAO, WANFEN

    2015-01-01

    Gonadotrophin-releasing hormone (GnRH) agonists (GnRHa) have been widely used to induce a state of downregulation for in vitro fertilization, and its direct effects on the pituitary are well known. However, the effects of GnRHa on the expression of anti-mullerian hormone (AMH) by follicles in varying stages in vivo remain to be fully elucidated. In the present study 84 cyclic mice were randomly divided equally into four GnRHa groups and three cyclic mice were used as a control group. The expression levels of AMH in follicles of varying stages between days 0 and 7 following GnRHa administration were quantified using immunohistochemistry. The expression of AMH in follicles at various stages revealed dynamic changes during the process of downregulation. AMH in primary follicles initially increased and then decreased gradually. In small and large preantral follicles and in granulosa cells (GCs) surrounding the oocyte of small antral follicles, the expression of AMH began to increase on day 1, was attenuated on day 2, and then increased to a peak. The expression levels of AMH in the GCs surrounding the basement membrane, in contrast to the GCs surrounding the oocyte, were significantly lower and did not increase on day 1. In all stages of follicles, the expression of AMH declined gradually between the peak level and last day of downregulation. On day 7, the varying follicular stages all expressed lower levels of AMH than on day 0. This decrease was more prominent in the higher dose groups, compared with the lower dose groups. In conclusion, GnRHa was observed to induce time-dependent changes in the expression of AMH at varying follicular stages, which occurred in a dose-dependent manner. PMID:26126720

  1. Exercise affects both ovarian follicular dynamics and hormone concentrations in mares.

    PubMed

    Kelley, D E; Gibbons, J R; Smith, R; Vernon, K L; Pratt-Phillip, S E; Mortensen, C J

    2011-09-01

    The objectives were to evaluate the effects of exercise on ovarian folliculogenesis and related hormones in mares. Mares (n = 11) were randomly assigned into a control (non-exercised) or treatment (exercised) group. Treatment mares (n = 5) were moderately exercised for 30 min, 6 d/wk. All mares underwent daily transrectal ultrasonographic examinations and ovarian follicles > 6 mm were measured. Blood samples were collected during the first (Cycle 1) and last (Cycle 4) cycle, and serum concentrations of cortisol, LH, and FSH were determined. Mean cortisol concentrations were elevated (P < 0.05) in exercised mares, 6.29 ± 0.22 compared with 5.62 ± 0.16 ng/dL (mean ± SEM), 30 min post exercise. There were no significant differences between groups in mean FSH concentrations; however, exercised mares had lower (17.3 ± 6.4 vs 41.1 ± 5.5 ng/mL; P < 0.05) peak LH concentrations. Furthermore, exercised mares experienced a longer (24.7 ± 0.8 vs 22.2 ± 0.8 d; P < 0.05) mean interovulatory interval for all cycles combined, fewer (P < 0.05) follicles 6 to 20 mm in diameter, and an increased (P < 0.05) number of follicles >20 mm following deviation. The dominant and largest subordinate follicle in exercised mares had a greater (P < 0.05) mean diameter on the day of deviation, suggesting delayed deviation. Exercised mares also tended (P = 0.06) to have an increased number of cycles with at least two dominant follicles compared to control (62 vs 36%, respectively), indicating a decreased ability of the largest follicle to assert dominance. Under the conditions of this study, moderately exercising mares induced higher cortisol concentrations, lowered peak LH concentrations, and altered ovarian follicular dynamics. PMID:21497892

  2. Age-related dynamics of follicles and hormones during an induced ovulatory follicular wave in mares.

    PubMed

    Ginther, O J; Gastal, M O; Gastal, E L; Jacob, J C; Beg, M A

    2009-03-15

    An ovulatory follicular wave was induced by ablation of follicles > or =6mm and treatment with prostaglandin F2alpha (PGF) on Day 10 (ovulation=Day 0). Follicle and hormone dynamics of the induced waves were compared among three age groups: young (5-6 y, n=14 waves), intermediate (10-14 y, n=16), and old (> or =18, n=15). During the common-growth phase of the induced wave (Days 12-17), diameter of the future ovulatory follicle was not different among ages, but the young group had more (P<0.05) follicles that reached > or =10mm. The number was correlated (r=+0.7; P<0.0001) within mares between consecutive interovulatory intervals, indicating repeatability. Concentrations of LH increased in all age groups during Days 12-17, but were greatest (P<0.002) in the young group and continued to be greater (P<0.0001) throughout the ovulatory LH surge. During several days before Day-1, there were no age-related effects on systemic estradiol concentrations, diameter of the preovulatory follicle, or B-mode echotexture or color-Doppler signals of blood flow in the follicle wall. Interpretations were: (1) greater number of follicles in the young group reflected a greater follicle reserve, (2) greater LH concentrations throughout the ovulatory surge in the young group reflected a more positive response to an extraovarian/environmental influence after removal of the negative effect of progesterone, and (3) lower LH concentrations in the older groups were adequate for the preovulatory changes in the follicle. PMID:19004489

  3. Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles.

    PubMed

    Vidali, Silvia; Knuever, Jana; Lerchner, Johannes; Giesen, Melanie; Bíró, Tamás; Klinger, Matthias; Kofler, Barbara; Funk, Wolfgang; Poeggeler, Burkhard; Paus, Ralf

    2014-01-01

    Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable. PMID:23949722

  4. The effect of endotoxin administration on the secretory dynamics of oxytocin in follicular phase mares: relationship to stress axis hormones.

    PubMed

    Alexander, S L; Irvine, C H G

    2002-07-01

    The primary aim of this study was to define the secretory dynamics of oxytocin and vasopressin in pituitary venous effluent from ambulatory horses during acute endotoxaemia, a stimulus that may release both hormones. Our secondary aim was to investigate the role of oxytocin in regulating adrenocorticotropic hormone (ACTH) secretion by comparing oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and ACTH secretory profiles during endotoxaemia and by monitoring the ACTH response to oxytocin administration. Pituitary venous blood was collected nonsurgically continuously and divided into 1-min segments from eight follicular phase mares. Four mares were sampled for 30 min before and 3.5 h after receiving an i.v. infusion of bacterial endotoxin (TOX). Four control mares were sampled for 2.5 h without infusion of TOX. Another three follicular phase mares were given 5 U of oxytocin to replicate the peak response to TOX and pituitary blood collected every 1 min for 10 min before and 15 min after injection. Endotoxin raised the secretion rates of all hormones measured. All hormones were released episodically throughout the experiment, with TOX increasing the amplitude of peaks in each hormone. Peaks in oxytocin and vasopressin were coincident in each treated mare. Similarly, ACTH peaks were coincident with peaks of oxytocin and vasopressin in each treated mare, and with peaks of CRH in three mares. However, oxytocin administration did not affect ACTH secretion. We conclude that during endotoxaemia in horses: (i) oxytocin and vasopressin are secreted synchronously; (ii) oxytocin is unlikely to be acting as an ACTH secretagogue since inducing peak oxytocin concentrations observed during TOX does not raise ACTH; and therefore (iii) the close relationship between oxytocin and ACTH secretion is circumstantial and due to the fact that oxytocin secretion is concurrent with that of vasopressin, a proven ACTH secretagogue in horses. PMID:12121490

  5. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  6. Influence of lameness on follicular growth, ovulation, reproductive hormone concentrations and estrus behavior in dairy cows

    PubMed Central

    Morris, M.J.; Kaneko, K.; Walker, S.L.; Jones, D.N.; Routly, J.E.; Smith, R.F.; Dobson, H.

    2011-01-01

    The objective of this study was to examine the effect of a chronic stressor, lameness, on reproductive parameters. Seventy cows 30–80 days post-partum were scored for lameness and follicular phases synchronized with GnRH followed seven days later by prostaglandin (PG). Fifteen Lame animals did not respond to GnRH ovarian stimulation. Milk progesterone for 5 days prior to PG was lower in the remaining Lame cows than Healthy herdmates. Fewer Lame cows ovulated (26/37 versus 17/18; P = 0.04) and the interval from PG to ovulation was shorter in Lame cows. In Subset 1 (20 animals), the LH pulse frequency was similar in ovulating animals (Lame and Healthy) but lower in Lame non-ovulators. An LH surge always preceded ovulation but lameness did not affect the interval from PG to LH surge onset or LH surge concentrations. Before the LH surge, estradiol was lower in non-ovulating cows compared to those that ovulated and estradiol concentrations were positively correlated with LH pulse frequency. In Subset 2 (45 cows), Lame ovulating cows had a less intense estrus than Healthy cows, although Lame cows began estrus and stood-to-be-mounted earlier than Healthy cows. In conclusion, we have identified several parameters to explain poor fertility in some chronically stressed animals. From 30 to 80 days post-partum, there was a graded effect that ranged from 29% Lame cows with absence of ovarian activity, whereas another 21% Lame cows failed to express estrus or ovulate a low estrogenic follicle; in 50% cows, many reproductive parameters were unaffected by lameness. PMID:21601262

  7. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Follicle-stimulating hormone test system. 862.1300... Systems § 862.1300 Follicle-stimulating hormone test system. (a) Identification. A follicle-stimulating hormone test system is a device intended to measure follicle-stimulating hormone (FSH) in plasma,...

  8. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

    EPA Science Inventory

    Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

  9. Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.

    PubMed

    Meijide, Susana; Hernández, M Luisa; Navarro, Rosaura; Larreategui, Zaloa; Ferrando, Marcos; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

    2014-10-01

    Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01). PMID:26461371

  10. Follicle-stimulating hormone (FSH) blood test

    MedlinePlus

    ... the test done on certain days of your menstrual cycle. ... In women, FSH helps manage the menstrual cycle and stimulates the ovaries to produce eggs. The test is used to help diagnose or evaluate: Menopause Women who have polycystic ovary ...

  11. Systemic concentrations of hormones during the development of follicular waves in mares and women: a comparative study

    PubMed Central

    Ginther, O J; Beg, M A; Gastal, E L; Gastal, M O; Baerwald, A R; Pierson, R A

    2010-01-01

    Changes in systemic concentrations of FSH, LH, oestradiol and progesterone during the ovulatory follicular wave were compared between 30 mares and 30 women. Based on a previous study, the emergence of the future ovulatory follicle was defined as occurring at 13.0 mm in mares and 6.0 mm in women, and deviation in diameter between the two largest follicles was expected to begin at 22.7 mm in mares and 10.3 mm in women. Mean FSH concentrations were high in mares during the luteal phase, resulting from statistically identified FSH surges occurring in individuals on different days and in different numbers (mean, 1.5 ± 0.2 surges/mare); the internadir interval was 3.9 ± 0.3 days. In contrast, mean FSH in women was low during the luteal phase and increased to a prolonged elevation during the follicular phase. The prolonged elevation was apparent in each individual (internadir interval, 15.2 ± 0.4 days). Changes in LH or oestradiol concentrations encompassing deviation were not detected in mares, but both hormones increased slightly but significantly between emergence and deviation in women. The hypothesis that a greater number of growing follicles causes a greater predeviation decrease in FSH was supported for mares (r, −0.39; P < 0.04), but a similar negative correlation (r, −0.36) was not significant in women. The hypothesis that the increase in oestradiol during the luteal phase in women was at least partly attributable to luteal-phase anovulatory follicular waves was not supported. Normalization of FSH concentrations to the day of emergence showed maximum value on the day of emergence with a significant increase and decrease on each side of emergence in both species. The day of expected deviation occurred 3 days after emergence during the decline in FSH in both species. These results indicated that the previously reported striking similarities in emergence and deviation between mares and women during the ovulatory follicular wave are associated with species

  12. KRAS(G12D)-mediated oncogenic transformation of thyroid follicular cells requires long-term TSH stimulation and is regulated by SPRY1.

    PubMed

    Zou, Minjing; Baitei, Essa Y; Al-Rijjal, Roua A; Parhar, Ranjit S; Al-Mohanna, Futwan A; Kimura, Shioko; Pritchard, Catrin; BinEssa, Huda; Alanazi, Azizah A; Alzahrani, Ali S; Akhtar, Mohammed; Assiri, Abdullah M; Meyer, Brian F; Shi, Yufei

    2015-11-01

    KRAS(G12D) can cause lung cancer rapidly, but is not sufficient to induce thyroid cancer. It is not clear whether long-term serum thyroid stimulating hormone (TSH) stimulation can promote KRAS(G12D)-mediated thyroid follicular cell transformation. In the present study, we investigated the effect of long-term TSH stimulation in KRAS(G12D) knock-in mice and the role of Sprouty1 (SPRY1) in KRAS(G12D)-mediated signaling. We used TPO-KRAS(G12D) mice for thyroid-specific expression of KRAS(G12D) under the endogenous KRAS promoter. Twenty TPO-KRAS(G12D) mice were given anti-thyroid drug propylthiouracil (PTU, 0.1% w/v) in drinking water to induce serum TSH and 20 mice were without PTU treatment. Equal number of wild-type littermates (TPO-KRAS(WT)) was given the same treatment. The expression of SPRY1, a negative regulator of receptor tyrosine kinase (RTK) signaling, was analyzed in both KRAS(G12D)-and BRAF(V600E)-induced thyroid cancers. Without PTU treatment, only mild thyroid enlargement and hyperplasia were observed in TPO-KRAS(G12D) mice. With PTU treatment, significant thyroid enlargement and hyperplasia occurred in both TPO-KRAS(G12D) and TPO-KRAS(WT) littermates. Thyroids from TPO-KRAS(G12D) mice were six times larger than TPO-KRAS(WT) littermates. Distinct thyroid histology was found between TPO-KRAS(G12D) and TPO-KRAS(WT) mice: thyroid from TPO-KRAS(G12D) mice showed hyperplasia with well-maintained follicular architecture whereas in TPO-KRAS(WT) mice this structure was replaced by papillary hyperplasia. Among 10 TPO-KRAS(G12D) mice monitored for 14 months, two developed follicular thyroid cancer (FTC), one with pulmonary metastasis. Differential SPRY1 expression was demonstrated: increased in FTC and reduced in papillary thyroid cancer (PTC). The increased SPRY1 expression in FTC promoted TSH-RAS signaling through PI3K/AKT pathway whereas downregulation of SPRY1 by BRAF(V600E) in PTC resulted in both MAPK and PI3K/AKT activation. We conclude that chronic TSH

  13. Effect of hormonal synchronisation and/or short-term supplementation with maize on follicular dynamics and hormone profiles in goats during the non-breeding season.

    PubMed

    Nogueira, D M; Cavalieri, J; Fitzpatrick, L A; Gummow, B; Blache, D; Parker, A J

    2016-08-01

    This study aimed to evaluate the reproductive response of anoestrous goats that were either hormonally treated and/or supplemented with maize for 9days to determine which treatment combination was the most effective in enhancing follicular development and ovulation rate, and whether these responses were associated with increases in metabolic hormones. The experiment was carried out using 28 does, using a 2×2 factorial design with seven does in each group to test the effect of synchronisation of oestrus, supplementation with maize and their interactions. Synchronisation of oestrous cycles (P<0.001) but not supplementation with maize or the interaction between the two (P>0.05) increased the number of codominant follicles, the diameter of the largest follicle on Day 9 and growth rate of follicles during the period of supplementation. Compared with non-supplemented animals, supplementation with maize increased the total number of follicles observed between Days 7 and 9 (P=0.039). In addition, nutritional supplementation with maize in combination with synchronisation of oestrus increased the ovulation rate by 43% (P=0.074). Interactions between time and supplementation with maize showed that plasma concentrations of insulin, leptin and IGF-1 were greater in does supplemented with maize compared with non-supplemented does (P<0.001). The findings show that hormonal synchronisation had the most influence on modifying follicular development and ovulation in anoestrous goats. Supplementation with maize increased the concentrations of insulin, leptin and IGF-1, which could potentially modify the sensitivity of follicles to gonadotrophins and reduce rates of atresia. PMID:27346587

  14. Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

    EPA Science Inventory

    Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

  15. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    SciTech Connect

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

  16. Rat growth-hormone release stimulators from fenugreek seeds.

    PubMed

    Shim, Sang Hee; Lee, Eun Ju; Kim, Ju Sun; Kang, Sam Sik; Ha, Hyekyung; Lee, Ho Young; Kim, Chungsook; Lee, Je-Hyun; Son, Kun Ho

    2008-09-01

    Bioassay-guided fractionation of MeOH extract from fenugreek (Trigonella foenum-graecum L.) seeds resulted in the isolation of two rat growth-hormone release stimulators in vitro, fenugreek saponin I (1) and dioscin (9), along with two new, i.e., 2 and 3, and five known analogues, i.e., 4-8. The structures of the new steroidal saponins, fenugreek saponins I, II, and III (1-3, resp.), were determined as gitogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, sarsasapogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, and gitogenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside, respectively. Fenugreek saponin I (1) and dioscin (9) caused ca. 12.5- and 17.7-fold stimulation of release, respectively, of rat growth hormone from rat pituitary cells, whereas gitogenin (5) showed moderate activity. To our knowledge, this is the first study to demonstrate that steroidal saponins stimulate rat growth-hormone release in rat pituitary cells. PMID:18816528

  17. Gonadotrophin releasing hormone treatment of Holstein cows with follicular cysts monitored by skim milk progesterone determination.

    PubMed

    Eissa, H M; el-Belely, M S

    1996-01-01

    Progesterone was assayed in skim milk fraction of 38 cystic cows, 26 (68.4%) of which had basal ( < 0.5 ng/ml) progesterone concentrations and were diagnosed as having follicular cysts. These cows were allotted at random to one of 3 treatments: (1) a sham injection of sterile water in 7 cows as controls; (2) a single injection (1 mg) of GnRH analog in 8 cows; (3) double injections (1 mg) of GnRH analog at 7-day interval in 11 cows. According to rectal palpation confirmed by skim milk progesterone determination, the double injection group responded well (P < 0.05) compared with the single injection and control groups (81.8% vs 62.5 vs 42.9%). The interval calving to 1st insemination, interval treatment to conception and interval calving to conception were significantly (P < 0.01) shorter in the double injection group than in the other 2 groups. Also, the conception rate to first insemination was significantly (P < 0.05) higher (63.6% vs 37.5% vs 42.9%). The data provide evidence for reduction in infertility and reproductive disorders in cystic cows given double injections of GnRH. PMID:8619276

  18. Pre-translational regulation of luteinizing hormone receptor in follicular somatic cells of cattle

    PubMed Central

    Marsters, P.; Kendall, N.R.; Campbell, B.K.

    2015-01-01

    Differential regulation of LHR in theca cells (TC) and granulosa cells (GC) is important for normal follicular development. Unlike TC, GC only acquire LH-responsiveness during the later stages of antral follicle development. This study tested the hypothesis that differential LH-responsiveness in these two cell types may be due, in part, to shifts in cellular patterns of alternatively spliced LHR mRNA transcripts which may not be obvious from analysis of total LHR gene expression. It also further explored the role of translation inhibition by an LHR binding protein (LHBP), normally associated with the production of endogenous cholesterol. LHR mRNA variation arises as a result of the alternative splicing of two variable deletion sites (VDS) designated 5′ VDS and 3′ VDS, and it was proposed that differences in cell sensitivity to LH may be due in part to variations in the pattern of the mRNA expression of the receptor variants. The outcomes of the present study support a dynamic multi-facetted regulation of LHR during pre-translation. Not only did the ratio between variants change during antral follicle growth and in vitro cell differentiation but also between TC and GC. Regulation could also be linked to LH concentration feedback mechanisms as the absence of LH caused cultured TC to markedly up-regulate amounts of LHR mRNA. In both TC and GC, LHR mRNA was greatly reduced after treatment to block mevalonate production in the de novo cholesterol pathway, adding further support for a regulatory mechanism linked to enriched cellular amounts of mevalonate kinase. PMID:26507944

  19. 76 FR 2807 - New Animal Drugs; Change of Sponsor; Follicle Stimulating Hormone

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ...; Follicle Stimulating Hormone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The... sponsor for a new animal drug application (NADA) for follicle stimulating hormone from Ausa International... hormone) to Therio, Inc., 8801 Anderson Ave., Manhattan, KS 66503. Accordingly, the Agency is amending...

  20. Nutritional state modulates growth hormone-stimulated lipolysis.

    PubMed

    Bergan, Heather E; Kittilson, Jeffrey D; Sheridan, Mark A

    2015-01-01

    Growth hormone (GH) regulates several processes in vertebrates, including two metabolically disparate processes: promotion of growth, an anabolic action, and mobilization of stored lipid, a catabolic action. In this study, we used hepatocytes isolated from continuously fed and long-term (4weeks) fasted rainbow trout (Oncorhynchus mykiss) as a model to investigate the mechanistic basis of the anabolic and catabolic actions of GH. Our hypothesis was that nutritional state modulates the lipolytic responsiveness of cells by adjusting the signal transduction pathways to which GH links. GH stimulated lipolysis as measured by increased glycerol release in both a time- and concentration-related manner from cells of fasted fish but not from cells of fed fish. Expression of mRNAs that encode the lipolytic enzyme hormone-sensitive lipase (HSL), HSL1 and HSL2, also was stimulated by GH in cells from fasted fish and not in cells from fed fish. Activation of the signaling pathways that mediate GH action also was studied. In cells from fed fish, GH activated the JAK-STAT, PI3K-Akt, and ERK pathways, whereas in cells from fasted fish, GH activated the PLC/PKC and ERK pathways. In hepatocytes from fasted fish, blockade of PLC/PKC and of the ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated HSL mRNA expression, whereas blockade of JAK-STAT or of the PI3K-Akt pathway had no effect on lipolysis or HSL expression stimulated by GH. These results indicate that during fasting GH activates the PLC/PKC and ERK pathways resulting in lipolysis but during periods of feeding GH activates a different complement of signal elements that do not promote lipolysis. These findings suggest that the responsiveness of cells to GH depends on the signal pathways to which GH links and helps resolve the growth-promoting and lipid catabolic actions of GH. PMID:25957918

  1. The effects of 3 gonadorelin products on luteinizing hormone release, ovulation, and follicular wave emergence in cattle

    PubMed Central

    Martínez, Marcelo F.; Mapletoft, Reuben J.; Kastelic, John P.; Carruthers, Terry

    2003-01-01

    The objective was to determine luteinizing hormone (LH) secretion and follicular dynamics in cattle following administration of 3 gonadorelin formulations that are commercially available in Canada. In experiment 1, nonlactating Holstein cows (n = 4 per group) were randomly assigned to receive 100 μg gonadorelin diacetate tetrahydrate, intramuscularly (C; Cystorelin, or FE; Fertagyl). Blood samples (for LH analysis) were collected 0, 1, 2, and 4 hours after treatment. In experiment 2, nonlactating Holstein cows (n = 10 per group) were randomly allocated to receive 100 μg gonadorelin, intramuscularly as follows: 2 mL of C; 1 mL of FE; or 2 mL of Factrel (FA, gonadorelin hydrochloride). Gonadorelin treatment was done on days 6 or 7 after ovulation and blood samples for LH analysis were collected at 0, 1, 2, 4, and 6 hours after treatment. Ovaries were examined by ultrasonography, twice daily, to detect ovulation. A replicate was conducted using only C (n = 10) or FE (n = 10); blood samples were collected at 0, 1, 2, 3, and 4 hours. In experiment 3, beef heifers (n = 10 per group) were randomly assigned to receive 1 of 3 GnRH gonadorelin treatments (as in the first phase of experiment 2) on days 6 or 7 after ovulation and blood samples were collected at 0, 0.5, 1, 1.5, 2, and 4 hours. In experiments 2 and 3, both mean and mean peak plasma LH concentrations were higher (P < 0.05) in cattle treated with C. The proportion of dominant follicles that ovulated was higher (P < 0.02) in Holstein cows treated with C than in those treated with FE or FA (18/19, 11/19, and 4/7, respectively), but there was no significant difference among the products in beef heifers (6/10, 6/10, and 4/10, respectively). No significant differences were found in the interval from treatment to the emergence of the next follicular wave. In summary, C induced a greater LH release and this resulted in a higher ovulatory rate in Holstein cows but not in beef heifers. PMID:12650040

  2. Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in euthyroid dogs.

    PubMed Central

    Sauvé, F; Paradis, M

    2000-01-01

    The purpose of this study was to evaluate the effects of the recombinant human thyroid-stimulating hormone (rhTSH) on serum total thyroxine (TT4) concentration in euthyroid dogs. Six healthy beagle dogs were used in each of the 3 phases of this study. Phase I: thyroid-stimulating hormone response tests were performed by using a total dose of 25 micrograms, 50 micrograms, and 100 micrograms of rhTSH, administered intravenously. Phases II and III: thyroid-stimulating hormone response tests were performed by using 50 micrograms of rhTSH administered by intramuscular and subcutaneous routes, respectively. In each phase and following all the administered doses of rhTSH, an increase in the serum TT4 concentration was noted, although it was not always significant. For phase I, there was a significant increase in serum TT4 concentrations. Based on this study, 50 micrograms was judged to be the optimal intravenous dose of rhTSH. For phases II and III, there was no significant increase in serum TT4 after the administration of rhTSH. Results of this study suggest that rhTSH could be a good substitute for bovine TSH, when used by the intravenous route, for the TSH stimulation test in dogs. Further studies are required to confirm its clinical usefulness. PMID:10738600

  3. Effects of dietary fat and season on steroid hormonal profiles before parturition and on hormonal, cholesterol, triglycerides, follicular patterns, and postpartum reproduction in Brahman cows.

    PubMed

    Lammoglia, M A; Willard, S T; Oldham, J R; Randel, R D

    1996-09-01

    Spring-calving Brahman cows (S) artificially inseminated to Brahman, Angus, or Tuli sires and fall-calving Brahman cows (F) naturally bred to Brahman were allotted randomly to receive 3.74% (LF; n = 9 S and 6 F), 5.20% (MF; n = 8 S and 6 F), or 6.55% dietary fat (HF; n = 8 S). Diets were formulated to contain differing fatty acid concentrations and to be isocaloric and isonitrogenous. Cows were bled and fed twice daily from 2 wk before expected calving date through d 21 after calving. Ultrasonography was performed on d 14 and 21 after calving. From d 21 to 90 after calving a sterile bull equipped with a chin-ball marker was placed with the cows to aid in estrus detection. In both seasons progesterone decreased (P < .01) and estradiol-17 beta increased (P < .01) as parturition approached. Cows receiving MF and HF had increased (P < .01) total numbers of follicles compared to LF cows, and cows receiving MF had larger (P < .01) follicles. During the spring, cows receiving HF and cows bred to Brahman or Tuli sires had longer (P < .01) gestation lengths. Progesterone concentrations before calving were affected (P < .01) by treatment x sire and estradiol-17 beta by a time x treatment interaction (P < .01). Cholesterol after calving was higher (P < .01) in HF cows than in LF or MF cows. In the fall, LF cows had heavier (P < .01) calves than cows receiving MF. Birth weight was also affected (P < .01) by treatment x sex of calf. Progesterone was affected (P < .01) by treatment x sex of calf. Estradiol-17 beta was affected (P < .01) by sex of calf and treatment x sex of calf. Across seasons, by d 90 after calving, 9 of 15 (60%) LF and 11 of 15 (73.3%) MF cows showed estrual behavior. Cows in the spring had increased (P < .01) numbers and larger follicles compared to the fall. In conclusion, dietary fat may influence steroid hormone concentrations before calving, calf birth weight and postpartum follicular populations; furthermore, follicular populations may also be

  4. Follicular correlates with in-vitro fertilization in cattle.

    PubMed

    Greve, T; Callesen, H; Hyttel, P

    1989-01-01

    The follicular microenvironment may affect the quality and the fertilizability of an oocyte in vivo as well as in vitro. Determination of the concentrations of certain follicular fluid compounds upon aspiration could therefore be used as important clinical measures to predict the developmental ability of an oocyte submitted to in-vitro fertilization. In cattle gonadotrophin stimulation (superovulation) frequently leads to perturbed follicular steroidogenesis and oocyte maturation, and fertilization rates in vivo as well as in vitro may be reduced. These abnormal changes are monitored in the peripheral profiles of LH, progesterone and oestradiol-17 beta during the periovulatory period, and measurements of these hormones may be used to discriminate between good and poor oocyte donors. Concurrent measurements of progesterone and oestradiol-17 beta in the aspirated follicular fluids and determination of the cytogenetic features of the oocytes will reflect these deviations but, because the variation between follicles within an animal is so large, it is not possible to rely on single hormone determinations; if attempted they should be interpreted with caution. Presently, no non-invasive method such as steroid measurement and flow cytometry accurately reflects oocyte quality and function in cattle and it is seriously questioned whether such clinically applicable methods are valid. It is suggested that evaluation of oocyte quality is done on three levels: (1) the animal (peripheral hormones), (2) the ovary (stimulation, premature ovulation, follicular appearance); and (3) the follicle (cumulus oophorus complex, steroids). PMID:2677342

  5. Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes.

    PubMed

    Dalterio, S L; Suter, D E; Schwartz, N B; Mayfield, D; Rettori, V B

    1986-07-01

    In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline-injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH

  6. Prediagnostic circulating follicle stimulating hormone concentrations and ovarian cancer risk.

    PubMed

    McSorley, Meghan A; Alberg, Anthony J; Allen, Diane S; Allen, Naomi E; Brinton, Louise A; Dorgan, Joanne F; Kaaks, Rudolf; Rinaldi, Sabina; Helzlsouer, Kathy J

    2009-08-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between prediagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, United Kingdom. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to 1 to 2 controls on age, menopausal status, time since last menstrual period, current hormone use and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend = 0.005). Compared with the lowest third of FSH concentrations, the OR among those in the middle and highest thirds were 0.45 [95% Confidence Interval (CI): 0.20-1.00] and 0.26 (95% CI: 0.10-0.70), respectively. Associations persisted after excluding cases diagnosed within 5 years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  7. Discordances between follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility

    PubMed Central

    2010-01-01

    Background Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients. Methods We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR. Results Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages. Discussion Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF. PMID:20565808

  8. Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in Assisted Reproduction

    PubMed Central

    Cahill, David; Gordon, Uma

    2013-01-01

    Data from 107 women undergoing their first IVF/ICSI were analyzed. Relationships between antimullerian hormone (AMH) and follicle stimulating hormone (FSH) were analyzed after dividing patients into four groups according to AMH/FSH levels. Concordance was noted in 57% of women (both AMH/FSH either normal or abnormal) while 43%of women had discordant values (AMH/FSH one hormone normal and the other abnormal). Group 1 (AMH and FSH in normal range) and group 2 (normal AMH and high FSH) were younger compared to group 3 (low AMH and normal FSH) and group 4 (both AMH/FSH abnormal). Group 1 showing the best oocyte yield was compared to the remaining three groups. Groups 3 and 4 required higher dose of gonadotrophins for controlled ovarian hyperstimulation showing their low ovarian reserve. There was no difference in cycle cancellation, clinical pregnancy, and live birth/ongoing pregnancy rate in all groups. These tests are useful to predict ovarian response but whether AMH is a substantially better predictor is not yet established. PMID:24454387

  9. Melatonin in human preovulatory follicular fluid

    NASA Technical Reports Server (NTRS)

    Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

    1987-01-01

    Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

  10. Hormonal stimulation of mitochondrial glutaminase. Effects of vasopressin, angiotensin II, adrenaline and glucagon.

    PubMed Central

    Corvera, S; García-Sáinz, J A

    1983-01-01

    Adrenaline (through alpha 1-adrenoceptors), vasopressin and angiotensin II stimulate mitochondrial glutaminase activity. This stimulation probably contributes to the ureogenic effect of these hormones. The activity of the enzyme is sensitive to Ca2+ depletion. A role of Ca2+ in hormonal modulation of glutaminase activity is suggested. PMID:6870814

  11. Diminished growth hormone secretion in blind males after L-dopa stimulation.

    PubMed

    Fatranská, M; Jurcovicová, J; Németh, S; Vigas, M

    1988-12-01

    Growth hormone secretion after L-dopa administration (1000 mg p.o.) was investigated in young adult normal and blind volunteers. The average increment of plasma growth hormone after L-dopa stimulation in the blind was below the criterion for a positive response (less than 5 ng ml-1). The control volunteers showed normal response. After L-dopa stimulation there was a significantly diminished growth hormone response in the young adult blind compared to control volunteers. PMID:3243205

  12. Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.

    PubMed

    Kushnir, Mark M; Naessén, Tord; Wanggren, Kjell; Hreinsson, Julius; Rockwood, Alan L; Meikle, A Wayne; Bergquist, Jonas

    2016-09-01

    Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF. PMID:26388251

  13. Profiles of thyrotropin, thyroid hormones, follicular cells and type I deiodinase gene expression during ontogenetic development of tilapia larvae and juveniles.

    PubMed

    Hsu, Chih-Wei; Tsai, Shu-Chuan; Shen, Shu Chane; Wu, Su Mei

    2014-10-01

    The aims of the present study are to determine whether triiodothyronine (T3) and/or thyroxine (T4) in tilapia larvae is gifted through the mother, and to investigate the change profiles of thyrotropin (TSH), thyroid follicular cells and type I deiodinase (D1) gene expression following larval development. T3 and T4 contents were measured using radioimmunoassay, thyrotropin was observed using immunocytochemistry, and the D1 gene was cloned and measured using real-time PCR. Results indicated that the β-TSH-immunoreactive cells (thyrotropin ICC) signals were detected at 9 dph (i.e., 9 days of post-hatching). Thyroid follicular cells were observed first at 3 dph, while the T3 contents of the whole body gradually decreased before 11 dph. T4 contents were detected until 13 dph, with higher secretion during 19-21 dph. In addition, the T3 synthesis was not inhibited by thiourea (TU) before 13 dph, but the TU response in the larvae appeared after 13 dph. Type I deiodinase (D1: GenBank accession number KC591724) was found to contain 2444 bases and encoded 248 amino acids. The D1 mRNA expression began to increase at 13 dph, with a higher expression during 15-19 dph. These results suggested that the T3 contents were maternally derived before 13 dph. Both thyroid hormonal changes and some parameters related to thyroid hormone synthesis in ontogenetic tilapia are discussed. PMID:24894980

  14. Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro.

    PubMed

    Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Nicoli, Alessia; Tagliavini, Simonetta; Trenti, Tommaso; La Sala, Giovanni Battista; Simoni, Manuela

    2016-02-15

    Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecular and physiological level. In this study, we demonstrated for the first time that co-treatment with a follicle-stimulating hormone (FSH) dose in the ART therapeutic range potentiates different LH- and hCG-dependent responses in vitro, measured in terms of cAMP, phospho-CREB, -ERK1/2 and -AKT activation, gene expression, progesterone and estradiol production in human granulosa-lutein cells (hGLC). We show that in the presence of FSH, hCG biopotency is about 5-fold increased, in the presence of FSH, in terms of cAMP activation. Accordingly, CREB phosphorylation and steroid production is increased under hCG and FSH co-treatment. LH effects, evaluated as steroidogenic cAMP/PKA pathway activation, do not change in the presence of FSH, which, however, increases LH-dependent ERK1/2 and AKT, but not CREB phosphorylation, resulting in anti-apoptotic effects. The different modulatory activity of FSH on LH and hCG action in vitro corresponds to their different physiological functions, reflecting proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy from the luteal phase onwards. PMID:26690776

  15. Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires β-catenin

    PubMed Central

    Parakh, Tehnaz N.; Hernandez, Jennifer A.; Grammer, Jean C.; Weck, Jennifer; Hunzicker-Dunn, Mary; Zeleznik, Anthony J.; Nilson, John H.

    2006-01-01

    Estrogens profoundly influence the physiology and pathology of reproductive and other tissues. Consequently, emphasis has been placed on delineating the mechanisms underlying regulation of estrogen levels. Circulating levels of estradiol in women are controlled by follicle-stimulating hormone (FSH), which regulates transcription of the aromatase gene (CYP19A1) in ovarian granulosa cells. Previous studies have focused on two downstream effectors of the FSH signal, cAMP and the orphan nuclear receptor steroidogenic factor-1 (NR5A1). In this report, we present evidence for β-catenin (CTNNB1) as an essential transcriptional regulator of CYP19A1. FSH induction of select steroidogenic enzyme mRNAs, including Cyp19a1, is enhanced by β-catenin. Additionally, β-catenin is present in transcription complexes assembled on the endogenous gonad-specific CYP19A1 promoter, as evidenced by chromatin immunoprecipitation assays. Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent regulation of this promoter is sensitive to alterations in the level of β-catenin. The stimulatory effect of β-catenin is mediated through functional interactions with steroidogenic factor-1 that involve four acidic residues within its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced Cyp19a1 mRNA accumulation. Together, these data demonstrate that β-catenin is essential for FSH/cAMP-regulated gene expression in the ovary, identifying a central and previously unappreciated role for β-catenin in estrogen biosynthesis, and a potential broader role in other aspects of follicular maturation. PMID:16895991

  16. Rescue from dominant follicle atresia by follicle-stimulating hormone in mice.

    PubMed

    Zhou, X L; Teng, Y; Cao, R; Fu, H; Xiong, K; Sun, W X; Zhu, C C; Huang, X J; Xiao, P; Liu, H L

    2013-01-01

    We investigated the effects of follicle-stimulating hormone (FSH) on atresia of the dominant follicle and changes in relevant apoptosis genes in granulosa cells of dominant follicles regulated by FSH in vivo. Four-week-old mice were administered FSH by intraperitoneal injection to induce follicular maturation. Granulosa cells of dominant follicles were collected at 48, 72, and 96 h after the first FSH injection. Phosphate-buffered saline was injected as a control. The mRNA levels of relevant granulosa cell apoptosis genes were examined by real-time quantitative polymerase chain reaction, and apoptosis of granulosa cells in dominant ovarian follicles was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis in granulosa cells of dominant follicles was almost TUNEL-negative at 48, 72-66, 72, and 96-90 h after the first FSH injection, but granulosa cell apoptosis in dominant follicles was clearly detected at 96, 102, and 102-96 h by TUNEL. The BIM, caspase-3, and caspase-9 mRNA expression levels were significantly lower after FSH treatment at 72-66 and 96-90 h, compared with that at 72 and 96 h (P < 0.05). Caspase-8 and FasL mRNA expressions did not respond to FSH. FSH rescued granulosa cells from apoptosis when the relevant apoptosis genes were upregulated in early atretic follicles. FSH did not rescue granulosa cells from apoptosis if the DNA was cut into fragments by endonucleases. Thus, the rescue by FSH of granulosa cells from apoptosis and dominant follicle atresia may be accomplished by inhibition of apoptosis in mitochondria. PMID:24065650

  17. The Relationships between Thyroid Hormones and Thyroid-stimulating Hormone with Lipid Profile in Euthyroid Men

    PubMed Central

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Aminuddin, Amilia; Johari, Mohamad Hanapi; Ngah, Wan Zurinah Wan

    2014-01-01

    Background and Aim: Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population. Methods: A total of 708 Chinese and Malay men aged 20 years and above were recruited in this cross-sectional study. Their blood was collected for the determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was analyzed using multiple regression and logistic regression models with adjustment for age, ethnicity, body mass index and FT4/FT3/TSH levels. Results: In multiple regression models, TSH was positively and significantly associated with TG (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C (p<0.05). In binary logistic models, an increase in TSH was significantly associated with higher prevalence of elevated TG in the subjects (p<0.05), while an increase in FT4 was significantly associated with higher prevalence of elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05). Free T3 was not associated with any lipid variables in the logistic regression (p>0.05). Conclusions: In euthyroid Malaysian men, there are positive and significant relationships between TSH level and TG level, and between FT4 level and cholesterol levels. PMID:24578612

  18. Transient neonatal hyperthyrotrophinaemia: a serum abnormality due to transplacentally acquired antibody to thyroid stimulating hormone.

    PubMed Central

    Lazarus, J H; John, R; Ginsberg, J; Hughes, I A; Shewring, G; Smith, B R; Woodhead, J S; Hall, R

    1983-01-01

    In a screening programme for neonatal hypothyroidism an otherwise healthy female infant was found to have a high concentration of thyroid stimulating hormone in a filter paper blood spot and in serum. A high concentration was also found in the maternal serum. Mother and baby were both biochemically euthyroid with normal serum thyroxine concentrations. The apparently high concentration of thyroid stimulating hormone in the mother was due to the presence of an IgG antibody that bound to human but not bovine thyroid stimulating hormone. Maternal serum inhibited the action of human thyroid stimulating hormone in an in vitro bioassay for the hormone. It is suggested that the baby acquired the antibody transplacentally, especially as the concentration of thyroid stimulating hormone subsequently fell. It is concluded that maternal serum should be assayed for thyroid stimulating hormone when a neonate is found to have a high concentration of the hormone and a normal concentration of thyroxine to establish the incidence of this finding and to avoid inappropriate replacement treatment. PMID:6402161

  19. Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program

    SciTech Connect

    Belkien, L.D.; Bordt, J.; Moeller, P.; Hano, R.; Nieschlag, E.

    1985-09-01

    A rapid and sensitive radioimmunoassay (RIA) was developed to compare serum and saliva estradiol (E/sub 2/) levels in patients undergoing ovulation induction in an in vitro fertilization and embryo transfer (IVF-ET) program. Serum and saliva E/sub 2/ were compared in 23 patients. The sensitivity of the saliva RIA standard curve was 11 fmol/tube (equal to 3.2 pg/tube). There was a highly significant correlation between serum and saliva E/sub 2/ throughout the stimulated cycles. The ratio of serum to saliva E/sub 2/ was constant throughout the stimulated cycles. The E/sub 2/ concentration per follicle was 1548 pmol/l in serum and 23 pmol/l in saliva. Mean E/sub 2/ levels in saliva (+/- SD) were 74 +/- 21 pmol/l at midcycle and 46 +/- 12 pmol/l at midluteal phase. The findings indicate that measurement of saliva E/sub 2/ provides a reliable, noninvasive method and may replace serum measurements for monitoring stimulated cycles in an IVF-ET program.

  20. Alteration in localization of steroid hormone receptors and coregulatory proteins in follicles from cows with induced ovarian follicular cysts.

    PubMed

    Salvetti, Natalia R; Alfaro, Natalia S; Velázquez, Melisa M L; Amweg, Ayelen N; Matiller, Valentina; Díaz, Pablo U; Ortega, Hugo H

    2012-12-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle. The altered follicular dynamics and cellular differentiation observed in COD may be mediated through a disruption of the expression of steroid receptors and their associated transcriptional cofactors. The aim of this study was to determine the protein expression profiles of ESR1, ESR2, PGR, AR, NCOA3, NCOR2, and PHB2 (REA) in ovarian follicles in an experimental model of COD induced by the administration of ACTH. Ovaries were collected and follicles were dissected from heifers during the follicular phase (control) or from heifers treated with ACTH to induce the formation of ovarian follicular cysts. Ovaries were fixed, sectioned, and stained immunohistochemically for steroid receptors and the associated transcription factors. The relative expression of ESR1 was similar in follicular cysts and in tertiary follicles from both control and cystic cows and was significantly higher than in secondary follicles. The expression of ESR2 in the granulosa was higher in cystic follicles. No differences were seen for PGR. The expression of androgen receptor was significantly increased in tertiary follicles with lower immunostaining in cysts. The expression of NCOA3 was observed in the granulosa and theca with a significantly increased expression in the theca interna of cystic follicles. The highest levels of NCOR2 expression in granulosa, theca interna, and theca externa were observed in cysts. In granulosa cells, NCOR2 levels increase progressively as follicles mature and the treatment had no effect. In summary, ovaries from animals with induced COD exhibited altered steroid receptor expression compared with normal animals, as well as changes in the expression of their regulators. It is reasonable to suggest that in conditions characterized by altered ovulation and follicular persistence, such as COD, changes in the intra-ovarian expression of these proteins could play a role in their pathogenesis

  1. Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis

    PubMed Central

    Mahran, Yasmen F.; El-Demerdash, Ebtehal; Nada, Ahmed S.; El-Naga, Reem N.; Ali, Azza A.; Abdel-Naim, Ashraf B.

    2015-01-01

    Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis. PMID:26465611

  2. Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women.

    PubMed

    Zhao, Ming Xu; Zhou, Guo Yu; Zhu, Jing Yuan; Gong, Biao; Hou, Jia Xiang; Zhou, Tong; Duan, Li Ju; Ding, Zhong; Cui, Liu Xin; Ba, Yue

    2015-09-01

    The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women. PMID:26464260

  3. Alpha-melanocyte stimulating hormone inhibits monocytes adhesion to vascular endothelium.

    PubMed

    Yang, Yang; Zhang, Weihua; Meng, Lin; Yu, Haitao; Lu, Na; Fu, Gang; Zheng, Yang

    2015-11-01

    Inflammation and its subsequent endothelial dysfunction have been reported to play a pivotal role in the initiation and progression of chronic vascular diseases. Inhibiting the attachment of monocytes to endothelium is a potential therapeutic strategy for vascular diseases treatment. α-Melanocyte stimulating hormone is generated from a precursor hormone called proopiomelanocortin by post-translational processing. However, whether α-melanocyte stimulating hormone plays a role in regulating endothelial inflammation is still unknown. In this study, the effects of α-melanocyte stimulating hormone on endothelial inflammation in human umbilical vein endothelial cell lines were investigated. And the result indicated that α-melanocyte stimulating hormone inhibits the expression of endothelial adhesion molecules, including vascular adhesion molecule-1 and E-selectin, thereby attenuating the adhesion of THP-1 cells to the surface of endothelial cells. Mechanistically, α-melanocyte stimulating hormone was found to inhibit NF-κB transcriptional activity. Finally, we found that the effect of α-melanocyte stimulating hormone on endothelial inflammation is dependent on its receptor melanocortin receptor 1. PMID:25898835

  4. Plasma steroid hormone concentrations and blood flow of the ovarian structures of the female dromedary (Camelus dromedarius) during growth, dominance, spontaneous ovulation, luteinization and regression of the follicular wave.

    PubMed

    Rawy, M S; Derar, R I; El-Sherry, T M; Megahed, G A

    2014-08-01

    The objectives of this study were to investigate the ovarian follicular waves and their corresponding hormonal changes in she-camels and to elucidate blood perfusion of the ovarian structures. Three reproductively sound, non-pregnant female camels were examined daily using B-mode and color Doppler to detect changes in their ovarian structures and blood vasculature for 22 follicular waves. Blood area (BA) and percentage (BA%) were determined for the ovarian structures. Three phases of follicular development, those of growth, maturation, and regression, were observed during each follicular wave. Deviation occurred on Day 6.1±1.08. Estradiol increased from basal levels of 27.4±0.4pg/ml to peak concentrations of 134.4±47.5pg/ml as the follicle reached a diameter of 13.2mm. Peripheral progesterone concentrations remained low (<0.4ng/ml) throughout the follicular waves. The blood flow to the dominant follicles increased gradually with follicular growth. The BA and BA% reached the maximum values of 18.4±11.6mm(2) and 6.04±2.03%, respectively, when the diameter of the dominant follicle was 17.5±3.4mm. The blood flow to the corpus luteum rose markedly after ovulation to reach a maximum BA% and BA at Days 5 and 7, respectively, post ovulation. In conclusion, the follicular wave pattern in dromedaries consists of individually variable periods of growth, maturation and regression. Deviation occurs 6.1±1.08d from emergence. Transrectal color-Doppler sonography is a useful technique for noninvasive evaluation of follicular vascularity in camels during various stages of the follicular wave. It provides additional information to assess the developmental stage and activity of the ovarian structures. PMID:24957969

  5. The influence of photoperiod on gonadotrophin-releasing hormone stimulated luteinising hormone release in the anoestrous mare.

    PubMed

    Nequin, L G; King, S S; Matt, K S; Jurak, R C

    1990-09-01

    The transition from anoestrus to oestrus in mares is controlled by photoperiod. The present study examined whether additional daylength would accelerate the mares' response to gonadotrophin-releasing-hormone (GnRH). Nine anoestrous mares were placed under ambient or artificial long lighting on 7th January. The four month experimental period was divided into a three-day sequence which was repeated at 21 day intervals. Ovaries were palpated rectally on Day 1; saline was injected (1 ml intravenously [iv]) on Day 2; GnRH was administered (0.59 microgram/kg bodyweight iv) on Day 3. Blood was taken at -60, 0, 15, 30, 60 and 120 mins relative to saline or GnRH treatment. Serum luteinising hormone (LH) was determined by a homologous equine radioimmunoassay (RIA). Several criteria were employed to define a positive response to GnRH and the results were analysed by Fisher's exact probability test. Treatment with artificial light allowed a response to GnRH within six weeks whereas the mares in ambient lighting took 12 weeks to respond to GnRH. The advancement in the time of response to GnRH under the long photoperiod could be related to changes in pituitary LH content, accelerated follicular activity or alterations in other brain-pituitary hormone levels. PMID:2226401

  6. Triclosan Blocks Mmp 13 Expression in Hormone-Stimulated Osteoblasts

    PubMed Central

    Barnes, Virginia Monsul; Xu, Tao; Shimizu, Emi; Jefcoat, Steven; Vasilov, Anatoliy; Qin, Ling; Partridge, Nicola C.

    2014-01-01

    Background Matrix metalloproteinase-13 (Mmp-13) is an important enzyme for the modulation of bone turnover and gingival recession. Elevated levels of Mmp-13 are associated with alveolar bone resorption, periodontal ligament destruction, and gingival attachment loss, which are the clinical symptoms of periodontal disease. Continued evidence suggests periodontal disease contributes to oral tissue destruction and is linked to numerous systemic conditions. Triclosan is a long standing, proven antibacterial and anti-inflammatory agent found in the only FDA-approved dentifrice for the treatment of plaque and gingivitis. Methods This study examined the inhibitory effects of triclosan on lipopolysaccharide (LPS), parathyroid hormone (PTH) and prostaglandin E2 (PGE2) induced expression of Mmp-13 in UMR 106-01 cells, an osteoblastic osteosarcoma cell line. The cells were stimulated with PTH or PGE2 to induce Mmp-13 mRNA expression and Real Time RT-PCR was performed to determine gene expression levels. Western blot analysis assessed the presence or absence of protein degradation or inhibition of protein synthesis. Mmp-13 Promoter Reporter Assay was utilized to explore possible direct effects of triclosan on the Mmp-13 promoter. Results Triclosan significantly reduced PTH or PGE2 elevated expression of Mmp-13 in osteoblastic cells without affecting basal levels of the mRNA. Surprisingly, triclosan enhanced the expression of c-fos and amphiregulin mRNA. A promoter assay indicated triclosan directly inhibits the activation of the PTH-responsive minimal promoter of Mmp-13. Conclusion Our data appear to have identified a nuclear mechanism of action of triclosan which accounts for triclosan’s ability to inhibit PTH or PGE2 induced Mmp-13 expression in osteoblastic cells. PMID:23368947

  7. Limited ability of circulating anti-Müllerian hormone to predict dominant follicular recruitment in PCOS women treated with clomiphene citrate: a comparison of two different assays.

    PubMed

    Vaiarelli, Alberto; Drakopoulos, Panagiotis; Blockeel, Christophe; De Vos, Michel; van de Vijver, Arne; Camus, Michel; Cosyns, Stefan; Tournaye, Herman; Polyzos, Nikolaos P

    2016-01-01

    The present retrospective cohort study was conducted to investigate whether serum anti-Müllerian hormone (AMH) levels, determined by either the Immunotech (IOT) or the second generation (Gen II) assay, can predict follicular recruitment in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). Patients received 50 mg CC daily for ovulation induction followed by natural intercourse or intrauterine insemination. Overall, 84 women had their serum AMH levels tested before treatment [42 patients with Immunotech (IOT), and 42 patients with the Gen II assay]. The primary outcome was to determine dominant follicle (>10 mm) recruitment in relation to AMH levels. Thirty-three (79%) patients in the IOT and 34 (81%) patients in the Gen II assay group developed a dominant follicle within 15 days after initiation of CC. Circulating AMH levels did not differ between women with or without dominant follicular recruitment in the both groups. By using either the AMH IOT or the Gen II assay, serum AMH levels were not predictive of the development of a dominant follicle. In conclusion, serum AMH levels measured by IOT or Gen II assay, has limited value to predict PCOS patients who will develop a dominant follicle following ovulation induction with CC. PMID:26559558

  8. Effect of thyroid stimulating hormone on adaptive behaviour in Down's syndrome.

    PubMed

    Bhaumik, S; Collacott, R A; Garrick, P; Mitchell, C

    1991-12-01

    Patients with Down's syndrome are particularly vulnerable to the development of both hypothyroidism and Alzheimer's disease. Both hypothyroidism and Alzheimer's disease may be associated with elevated serum concentrations of thyroid stimulating hormone. In a group of institutionalized Down's syndrome patients with normal thyroid function, global scores of ability were higher than in a group of patients with elevated thyroid stimulating hormone levels in the presence of normal T3 and T4. The actual concentrations of thyroid stimulating hormone were shown to be significantly and inversely correlated with scores of global abilities. If these findings are reproducible, the authors believe that thyroid stimulating hormone estimation may provide confirmatory evidence of clinical dementia in this group of mentally handicapped individuals. PMID:1839315

  9. Responses of luteinizing hormone, follicle-stimulating hormone, and prolactin to prolonged administration of the dopamine antagonist in normal women and women with low-weight amenorrhea.

    PubMed

    Larsen, S

    1981-06-01

    The responses of luteinizing hormone, follicle-stimulating hormone, and prolactin to prolonged administration of the dopamine receptor antagonist metoclopramide (5 mg twice daily) were investigated in six normal women and six women with low-weight amenorrhea (LWA). In contrast to the normal group, the LWA group showed no significant changes in the mean basal prolactin level or the mean prolactin response to stimulation with thyrotropin-releasing hormone, but there was an significant elevation of the mean net increase in luteinizing hormone after stimulation with gonadotropin-releasing hormone. On the basis of these data, the possibility of increased central dopaminergic activity in women with LWA is discussed. PMID:6788608

  10. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  11. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    SciTech Connect

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  12. A new insertion/deletion fragment polymorphism of inhibin-α gene associated with follicular cysts in Large White sows

    PubMed Central

    LI, Wanhong; CHEN, Shuxiong; LI, Hongjiao; LIU, Zhuo; ZHAO, Yun; CHEN, Lu; ZHOU, Xu; LI, Chunjing

    2015-01-01

    Ovarian follicular cysts are anovulatory follicular structures that lead to infertility. Hormones play key roles in the formation and persistence of cysts. Inhibins are heterodimeric gonadal glycoprotein hormones that belong to the transforming growth factor-β superfamily. These hormones suppress the secretion of follicle-stimulating hormone. In this report, partial fragment of inhibin-α (INHA) subunit gene of Large White pig was detected from the genomic DNA by polymerase chain reaction. The sequence showed a 283 bp fragment insertion/deletion (I/D) polymorphism in INHA subunit gene. A total of 49 Large White sows with cystic follicles and 152 normal sows were screened for this polymorphism. The relationship of INHA I/D polymorphisms with follicular cysts was investigated. The distribution of I/D was significantly different between cystic and normal sows, thereby suggesting that the INHA subunit gene might be a potential biological marker for breeding programs in pig. PMID:26521695

  13. A new insertion/deletion fragment polymorphism of inhibin-α gene associated with follicular cysts in Large White sows.

    PubMed

    Li, Wanhong; Chen, Shuxiong; Li, Hongjiao; Liu, Zhuo; Zhao, Yun; Chen, Lu; Zhou, Xu; Li, Chunjing

    2016-05-18

    Ovarian follicular cysts are anovulatory follicular structures that lead to infertility. Hormones play key roles in the formation and persistence of cysts. Inhibins are heterodimeric gonadal glycoprotein hormones that belong to the transforming growth factor-β superfamily. These hormones suppress the secretion of follicle-stimulating hormone. In this report, partial fragment of inhibin-α (INHA) subunit gene of Large White pig was detected from the genomic DNA by polymerase chain reaction. The sequence showed a 283 bp fragment insertion/deletion (I/D) polymorphism in INHA subunit gene. A total of 49 Large White sows with cystic follicles and 152 normal sows were screened for this polymorphism. The relationship of INHA I/D polymorphisms with follicular cysts was investigated. The distribution of I/D was significantly different between cystic and normal sows, thereby suggesting that the INHA subunit gene might be a potential biological marker for breeding programs in pig. PMID:26521695

  14. Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation

    PubMed Central

    Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

    2015-01-01

    Objective The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. Methods We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). Results 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. Conclusions The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro. PMID:26241313

  15. Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone

    SciTech Connect

    Moon, Y.S.; Duleba, A.; Leung, P.C.; Gomel, V.

    1982-03-15

    Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period.

  16. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

    SciTech Connect

    Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A. )

    1988-07-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery.

  17. An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

    PubMed Central

    Kuechler, Amla; Hauffa, Berthold P; Köninger, Angela; Kleinau, Gunnar; Albrecht, Beate; Horsthemke, Bernhard; Gromoll, Jörg

    2010-01-01

    Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C>A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163 kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance. PMID:20087398

  18. Androgen receptor and miRNA-126* axis controls follicle-stimulating hormone receptor expression in porcine ovarian granulosa cells.

    PubMed

    Du, Xing; Li, Qiqi; Pan, Zengxiang; Li, Qifa

    2016-08-01

    Androgen, which acts via the androgen receptor (AR), plays crucial roles in mammalian ovarian function. Recent studies showed that androgen/AR signaling regulates follicle-stimulating hormone receptor (FSHR) expression in follicles; however, the detailed mechanism underlying this regulation remained unknown. Here, we demonstrate that AR and miR-126* cooperate to inhibit FSHR expression and function in pig follicular granulosa cells (pGCs). In pGCs, overexpression of AR decreased, whereas knockdown increased, FSHR mRNA and protein expression; however, neither manipulation affected FSHR promoter activity. Using a dual-luciferase reporter assay, we found that the FSHR gene is a direct target of miR-126*, which inhibits FSHR expression and increases the rate of AR-induced apoptosis in pGCs. Collectively, our data show for the first time that the AR/miR-126* axis exerts synergetic effects in the regulation of FSHR expression and apoptosis in pGCs. Our findings thus define a novel pathway, AR/miR-126*/FSHR, that regulates mammalian GC functions. PMID:27222597

  19. Follicular and endocrinological turnover associated with GnRH induced follicular wave synchronization in Indian crossbred cows.

    PubMed

    Satheshkumar, S; Subramanian, A; Devanathan, T G; Kathiresan, D; Veerapandian, C; Palanisamy, A

    2012-04-01

    The goal of this study was to record the hormonal and follicular turnover in Jersey crossbred cows when subjected for follicular wave synchronization using GnRH. Six healthy, non-lactating and regularly cycling Jersey crossbred cows (5-6 y) were used for the study. In the control group, the follicular wave pattern was ultrasonographically investigated in 18 cycles (3 cycles/cow). In the treatment group, GnRH analogue (buserelin acetate 10 μg im) was administered on Day 6 of the cycle and follicular wave pattern was studied in 12 cycles (2 cycles/animal). Follicular population was categorized based on their diameter Class I, ≤5 mm; Class II, >5-<9 mm; Class III, ≥9 mm) and the number of follicles in each category was determined on Day 6, Day 8 and Day 10. Plasma FSH and progesterone concentrations were estimated in both control and treatment groups. Out of 18 estrous cycles studied, 14 cycles (77.8%), three cycles (16.7%) and one cycle (5.6%) exhibited three-, two- and four-follicular waves per cycle, respectively. It was evident that the DF of Wave I established its dominance and was in the growing phase by Day 6 of the estrous cycle in all the normally cycling crossbred cows. The DF ovulated in all the animals (100%) in the mean interval of 27.7 ± 0.2 h after GnRH administration. A synchronized homogenous group of follicles emerged two days after GnRH injection (Day of 8.0 ± 0.0) in all the animals (100%). The combination of LH surge induced ovulation of DF (abrupt termination of Wave I) and FSH surge stimulated homogenous recruitment of Class I follicles, led to a synchronized emergence of follicular wave. All the GnRH treated cows had three follicular waves because of early emergence and short period of dominance of Wave II DF. PMID:22192396

  20. Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol

    PubMed Central

    Park, Chan Woo; Hwang, Yu Im; Koo, Hwa Seon; Kang, Inn Soo; Yang, Kwang Moon

    2014-01-01

    Objective To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). Methods A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. Results The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). Conclusion The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials. PMID:25599038

  1. Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor

    PubMed Central

    Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Fave, Gianfranco Delle; Jensen, Robert T.

    2012-01-01

    Foregut Neuroendocrine Tumors[NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor(EGFR) by growth factors, gastrointestinal(GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGFα and various GI hormones to stimulate growth of the human foregut carcinoid, BON, the somatostatinoma QGP-1 and the rat islet tumor, Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGFα and the other growth-stimulating GI hormones increased Tyr1068 EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs. PMID:23220008

  2. Thyroid hormone stimulation of plasma protein synthesis in cultured hepatocytes.

    PubMed

    Hertzberg, K M; Pindyck, J; Mosesson, M W; Grieninger, G

    1981-01-25

    The direct effect of thyroid hormones on hepatocellular plasma protein synthesis has been studied in primary monolayer cultures derived from chick embryo liver. The chemically defined medium used for plating and maintaining the cultures contained no other hormones, protein, or serum supplement. Addition of physiological concentrations (10 nM) of triiodothyronine or thyroxine produced 3-fold or greater increases in the rates of synthesis of fibrinogen and three other major secreted proteins. By comparison albumin, transferrin, and total protein synthesis were not substantially increased. The enhanced synthesis of selected plasma proteins could be detected 6 h after initial addition of triiodothyronine. Exposure of the cells to the hormone for only 30 min was nearly as effective as continuous exposure in eliciting the ultimate response. Triiodothyronine exerted its half-maximal effect at a concentration of 1 nM. Diminished potency was associated with less iodination of the hormone; a marked reduction was noted with di-iodinated thyronine and no stimulatory activity at all with either mono- or non-iodinated thyronine. PMID:7451459

  3. Serum thyroid stimulating hormone (TSH) in malnutrition: preliminary results.

    PubMed

    Osman, A; Khalid, B A; Tan, T T; Wan Nazaimoon, W M; Wu, L L; Ng, M L

    1993-06-01

    This is a report of a cross sectional study involving 3 groups of children, moderately malnourished (BMI < 15), mildly malnourished (BMI 15-18) and well nourished (BMI > 18) to determine the differences in hormonal and biochemical parameters between the groups. The children were of age range from 7-17 years old. The children were from the same area with exposure to the same food, drinking water and environment. There were significant differences in the nutritional indices between the three groups. No differences were observed in levels of triiodothyronine (T3), thyroxine (T4) and T3:T4 ratio. Significant difference however was found in the TSH levels using highly sensitive IRMA TSH assays. Moderately malnourished children had higher TSH levels (p < 0.05) compared to mildly malnourished and well-nourished children. No difference was found between the mildly malnourished and well-nourished groups. There were no significant differences in serum cortisols done at similar times, fasting growth hormone and calcium. Serum alanine transminase (ALT) however was higher in moderately malnourished than in well-nourished children. Thus using highly sensitive IRMA TSH assays, we were able to detect differences in TSH levels even though T3, T4 and T3:T4 ratio, cortisol, growth hormone and calcium were normal, implying in moderately malnourished children, a higher TSH drive to maintain euthyroid state. PMID:8266178

  4. Thyroid hormone stimulation in vitro of red blood cell Ca2+-ATPase activity: interspecies variation.

    PubMed

    Davis, F B; Kite, J H; Davis, P J; Blas, S D

    1982-01-01

    In vitro susceptibility to thyroid hormone stimulation of membrane-associated Ca2+-ATPase activity has been examined in red blood cells from rat, rabbit, dog, monkey, and man. Monkey and human red cell Ca2+-ATPase activities responded comparably to 10(-10)M T4 or T3. Basal and thyroid hormone-stimulated Ca2+-ATPase activity in rabbit erythrocytes was four-fold higher than in primate red cells. Rat and dog red cell Ca2+-ATPase did not respond to iodothyronines in vitro. PMID:6459228

  5. Stimulation of hormone-responsive adenylate cyclase activity by a factor present in the cell cytosol.

    PubMed Central

    MacNeil, S; Crawford, A; Amirrasooli, H; Johnson, S; Pollock, A; Ollis, C; Tomlinson, S

    1980-01-01

    1. Homogenates of whole tissues were shown to contain both intracellular and extracellular factors that affected particulate adenylate cyclase activity in vitro. Factors present in the extracellular fluids produced an inhibition of basal, hormone- and fluoride-stimulated enzyme activity but factors present in the cell cytosol increased hormone-stimulated activity with relatively little effect on basal or fluoride-stimulated enzyme activity. 2. The existence of this cytosol factor or factors was investigated using freshly isolated human platelets, freshly isolated rat hepatocytes, and cultured cells derived from rat osteogenic sarcoma, rat calvaria, mouse melanoma, pig aortic endothelium, human articular cartilage chondrocytes and human bronchial carcinoma (BEN) cells. 3. The stimulation of the hormone response by the cytosol factor ranged from 60 to 890% depending on the tissue of origin of the adenylate cyclase. 4. In each case the behaviour of the factor was similar to the action of GTP on that particular adenylate cyclase preparation. 5. No evidence of tissue or species specificity was found, as cytosols stimulated adenylate cyclase from their own and unrelated tissues to the same degree. 6. In the human platelet, the inclusion of the cytosol in the assay of adenylate cyclase increased the rate of enzyme activity in response to stimulation by prostaglandin E1 without affecting the amount of prostaglandin E1 required for half-maximal stimulation or the characteristics of enzyme activation by prostaglandin E. PMID:7396869

  6. Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal.

    PubMed

    Yu, Jie; Berga, Sarah L; Johnston-MacAnanny, Erika B; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

    2016-06-01

    Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity. PMID:27035651

  7. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs*

    PubMed Central

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-01-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH). PMID:26642181

  8. Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause

    PubMed Central

    Rył, Aleksandra; Jasiewicz, Andrzej; Grzywacz, Anna; Adler, Grażyna; Skonieczna-Żydecka, Karolina; Rotter, Iwona; Sipak-Szmigiel, Olimpia; Rumianowski, Bogdan; Karakiewicz, Beata; Jurczak, Anna; Parczewski, Miłosz; Urbańska, Anna; Grabowska, Marta; Laszczyńska, Maria

    2016-01-01

    Background: Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman’s body after menopause and different genetic variants are still being sought. Methods: The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE) and lepitn (LEP) genotypes were determined by real-time PCR and polymerase chain reaction–restriction fragment length polymorphism, respectively. Results: We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. Conclusions: To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels. PMID:27240396

  9. Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

    PubMed

    Turkmen, S; Backstrom, T; Idil, M

    2004-08-01

    We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary. PMID:15624268

  10. Anti-Müllerian Hormone Levels in the Follicular Fluid of the Preovulatory Follicle: A Predictor for Oocyte Fertilization and Quality of Embryo

    PubMed Central

    2014-01-01

    This prospective study investigated the relationship between anti-Müllerian hormone (AMH) level in the follicular fluid (FF) and the quality of the oocyte and embryo. A total of 65 FF samples from 54 women were included in this study. FF was collected from the largest preovulatory follicle sized≥20 mm of mean diameter from each ovary. Samples were divided into 3 groups according to the FF AMH levels: below the 33th percentile (low group, FF AMH<2.1 ng/mL, n=21), between the 33th and the 67th percentile (intermediate group, FF AMH=2.1-3.6 ng/mL, n=22), and above the 67th percentile (high group, FF AMH>3.6 ng/mL, n=22). The quality of the ensuing oocytes and embryos was evaluated by fertilization rate and embryo score. FF AMH levels correlated positively with the matched embryo score on day 3 after fertilization (r=0.331, P=0.015). The normal fertilization rate was significantly lower in the low group than in the intermediate group (61.9% vs. 95.5% vs. 77.3%, respectively, P=0.028). Our results suggest that the FF AMH level could be a predictor of the ensuing oocyte and embryo quality. Graphical Abstract PMID:25246746

  11. Relationships between hormone-induced calcium release and 86rubidium uptake stimulation in starfish oocytes.

    PubMed

    Guerrier, P; Moreau, M; Dorée, M

    1979-09-01

    86Rubidium+ uptake, but not 86Rubidium efflux, is strongly stimulated after addition of the meiosis inducing hormone 1-methyladenine (1-MeAde) to prophase blocked oocytes of the starfish Marthasterias glacialis. This stimulation is a transient process which does not require the continuous presence of 1-MeAde and is elicited within 1 minute of contact. 1-MeAde and its biologically active structural analogs fully stimulate Rb+ uptake at concentrations which are about two orders of magnitude lower than those required to trigger meiosis reinitiation but which already release underthreshold levels of Ca2+ from the inner part of the plasma membrane. External Ca2+ concentrations effective in triggering meiosis reinitiation also stimulate Rb+ influx, while drugs like D600, theophyllin and caffein which suppress the hormone induced Ca2+ release, simultaneously preclude the stimulation of Rb+ uptake. Dithiothreitol (DTT) which mimicks 1-MeAde action in releasing Ca2+ and inducing meiosis acts both on the efflux and on active and passive Rb+ influxes. Ouabain, the classical inhibitor of the Na+, K+ pump does not preclude meiosis reinitiation under the influence of 1-MeAde, its agonists of mimetics. It suppresses the active component of Rb+ uptake both in control or stimulate oocytes. When applied only in preincubation before starting the hormone treatment, it cannot however inhibit the stimulation of Rb+ uptake, while basal pump inhibition is preserved. These results demonstrate that stimulation of the active Rb+ or K+ transport is not indispensable to meiosis reinitiation. They suggest moreover that the hormone induced Ca2+ release from the plasma membrane may be responsible for unmasking new ouabain sensitive transport sites. PMID:515475

  12. Risk assessment of thyroid follicular cell tumors.

    PubMed Central

    Hill, R N; Crisp, T M; Hurley, P M; Rosenthal, S L; Singh, D V

    1998-01-01

    Thyroid follicular cell tumors arise in rodents from mutations, perturbations of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1) chemically induced rodent thyroid tumors are presumed to be relevant to humans; 2) when interspecies information is lacking, the default is to assume comparable carcinogenic sensitivity in rodents and humans; 3) adverse rodent noncancer thyroid effects due to chemically induced thyroid-pituitary disruption are presumed to be relevant to humans; 4) linear dose-response considerations are applied to thyroid cancer induced by chemical substances that either do not disrupt thyroid functioning or lack mode of action information; 5) nonlinear thyroid cancer dose-response considerations are applied to chemicals that reduce thyroid hormone levels, increase TSH and thyroid cell division, and are judged to lack mutagenic activity; and 6) nonlinear considerations may be applied in thyroid cancer dose-response assessments on a case-by-case basis for chemicals that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity. Required data for risk assessment purposes is mode of action information on mutagenicity, increases in follicular cell growth (cell size and number) and thyroid gland weight, thyroid-pituitary hormones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effects when dosing ceases. Images Figure 1 Figure 2 Figure 3 PMID:9681971

  13. Comparative glycomics of the glycoprotein follicle stimulating hormone: glycopeptide analysis of isolates from two mammalian species.

    PubMed

    Dalpathado, Dilusha S; Irungu, Janet; Go, Eden P; Butnev, Vladimir Y; Norton, Katie; Bousfield, George R; Desaire, Heather

    2006-07-18

    Follicle stimulating hormone (FSH) is one of the important hormones that regulate gonadal functions. This hormone is glycosylated, and the glycans greatly influence the biological properties. In the present study the negatively charged glycopeptides of equine and human pituitary follicle stimulating hormone (eFSH and hFSH) have been characterized in a glycosylation site-specific manner using FT-ICR-MS and Edman sequencing. The characteristic pattern of glycan distribution at each glycosylation site has been deduced and compared between horse and human FSH preparations. The data suggest that site-specific differences exist between glycoforms of human and equine FSH. For instance, except for one site in the beta subunit (Asn7) of hFSH all other sites in both species have sulfated glycoforms. Also, glycoforms at Asn52 of hFSH are all complex type, whereas in eFSH, both complex and hybrid structures exist at this site. There is also a higher percentage of sulfated glycans in the latter site compared to the former. This is the first study that characterizes the glycans from this hormone in a glycosylation site-specific manner, and these data can be used to begin correlative studies between glycosylation structure and hormone function. PMID:16834341

  14. Gamma-melanocyte-stimulating hormone-like immunoreactivity in blood cells of human eosinophilic patients.

    PubMed

    Johansson, O; Virtanen, M; Hilliges, M; Hansson, L O

    1991-01-01

    The immunohistochemical localization of the peptide gamma-melanocyte-stimulating hormone (gamma-MSH) within human polymorphonuclear leucocytes of blood from eosinophilic patients is described. The gamma-MSH immunoreactivity was observed only in neutrophilic granulocytes leaving all other cell types immuno-negative. PMID:1805488

  15. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Follicle-stimulating hormone test system. 862.1300 Section 862.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  16. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Follicle-stimulating hormone test system. 862.1300 Section 862.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  17. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Follicle-stimulating hormone test system. 862.1300 Section 862.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  18. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Follicle-stimulating hormone test system. 862.1300 Section 862.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  19. Thyroid stimulating hormone microadenoma as a rare cause of thyrotoxicosis amenable to surgical cure.

    PubMed

    Turel, Mazda K; Asha, Hesarghatta S; Rajaratnam, Simon; Chacko, Geeta; Chacko, Ari G

    2012-06-01

    Hyperthyroidism due to a thyroid stimulating hormone (TSH) pituitary adenoma is rare. We report a 29-year-old woman with thyrotoxicosis and elevated serum 3,5,3',5'-tetraiodothyronine and TSH levels that resolved after a transsphenoidal excision of the detected TSH pituitary adenoma. The diagnosis and management options in such patients are reviewed. PMID:22153796

  20. NEONATAL SYMPATHECTOMY COMPROMISES DEVELOPMENT OF RESPONSES OF ORNITHINE DECARBOXYLASE TO HORMONAL STIMULATION IN PERIPHERAL TISSUES

    EPA Science Inventory

    The onset of sympathetic innervation has been shown to play a role in the development of postsynaptic reactivity to stimulation. n the current study, we examined whether this relationship extends to responses evoked by hormonal stimuli. ats denervated at birth by 6-hydroxydopamin...

  1. Role of the Extracellular and Intracellular Loops of Follicle-Stimulating Hormone Receptor in Its Function

    PubMed Central

    Banerjee, Antara A.; Mahale, Smita D.

    2015-01-01

    Follicle-stimulating hormone receptor (FSHR) is a leucine-rich repeat containing class A G-protein coupled receptor belonging to the subfamily of glycoprotein hormone receptors (GPHRs), which includes luteinizing hormone/choriogonadotropin receptor (LH/CGR) and thyroid-stimulating hormone receptor. Its cognate ligand, follicle-stimulating hormone binds to, and activates FSHR expressed on the surface of granulosa cells of the ovary, in females, and Sertoli cells of the testis, in males, to bring about folliculogenesis and spermatogenesis, respectively. FSHR contains a large extracellular domain (ECD) consisting of leucine-rich repeats at the N-terminal end and a hinge region at the C-terminus that connects the ECD to the membrane spanning transmembrane domain (TMD). The TMD consists of seven α-helices that are connected to each other by means of three extracellular loops (ELs) and three intracellular loops (ILs) and ends in a short-cytoplasmic tail. It is well established that the ECD is the primary hormone binding domain, whereas the TMD is the signal transducing domain. However, several studies on the ELs and ILs employing site directed mutagenesis, generation of chimeric receptors and in vitro characterization of naturally occurring mutations have proven their indispensable role in FSHR function. Their role in every phase of the life cycle of the receptor like post translational modifications, cell surface trafficking, hormone binding, activation of downstream signaling, receptor phosphorylation, hormone–receptor internalization, and recycling of hormone–receptor complex have been documented. Mutations in the loops causing dysregulation of these processes lead to pathophysiological conditions. In other GPHRs as well, the loops have been convincingly shown to contribute to various aspects of receptor function. This review article attempts to summarize the extensive contributions of FSHR loops and C-terminal tail to its function. PMID:26236283

  2. The herding hormone: oxytocin stimulates in-group conformity.

    PubMed

    Stallen, Mirre; De Dreu, Carsten K W; Shalvi, Shaul; Smidts, Ale; Sanfey, Alan G

    2012-01-01

    People often conform to others with whom they associate. Surprisingly, however, little is known about the possible hormonal mechanisms that may underlie in-group conformity. Here, we examined whether conformity toward one's in-group is altered by oxytocin, a neuropeptide often implicated in social behavior. After administration of either oxytocin or a placebo, participants were asked to provide attractiveness ratings of unfamiliar visual stimuli. While viewing each stimulus, participants were shown ratings of that stimulus provided by both in-group and out-group members. Results demonstrated that on trials in which the ratings of the in-group and out-group were incongruent, the ratings of participants given oxytocin conformed to the ratings of their in-group but not of their out-group. Participants given a placebo did not show this in-group bias. These findings indicate that administration of oxytocin can influence subjective preferences, and they support the view that oxytocin's effects on social behavior are context dependent. PMID:22991128

  3. Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action.

    PubMed Central

    D'Costa, M A; Angel, A

    1975-01-01

    The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis. Images PMID:162783

  4. Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells1

    PubMed Central

    Hoang, Yvonne D.; Nakamura, Brooke N.; Luderer, Ulrike

    2009-01-01

    Glutathione (GSH), the most abundant intracellular nonprotein thiol, is critical for many cellular functions. The rate-limiting step in GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The tissue-specific regulation of GSH synthesis is poorly understood. We showed previously that gonadotropin hormones regulate ovarian GSH synthesis. In the present study, we sought to clarify the ovarian cell type-specific effects of follicle-stimulating hormone (FSH) and estradiol on GSH synthesis. Immature female rats were treated with estradiol to stimulate development of small antral follicles. Granulosa cells (GCs) from these follicles or whole follicles were cultured in serum-free media, with or without FSH and 17beta-estradiol. The GSH and GCLC protein and mRNA levels increased in GCs treated with FSH alone. The effects of FSH on GCLC and GCLM protein and mRNA levels, GCL enzymatic activity, and GSH concentrations in GCs were significantly enhanced by the addition of estradiol. Estradiol alone had no effects on GSH. Dibromo-cAMP mimicked and protein kinase A (PKA) inhibitors prevented FSH stimulation of GCL subunit protein levels. In cultured small antral follicles, FSH stimulated estradiol synthesis and robustly increased GCL subunit mRNA and protein levels and GSH concentrations. The GCL subunit mRNA expression increased in both the granulosa cells and theca cells of follicles with FSH stimulation. These data demonstrate that maximal stimulation of GSH synthesis by FSH in granulosa cells and follicles requires estradiol. Without estradiol, FSH causes lesser increases in GCL subunit expression via a PKA-dependent pathway. PMID:19516019

  5. Is anti-mullerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix?

    PubMed Central

    Browne, Hyacinth N.; Moon, Kimberly S.; Mumford, Sunni L.; Schisterman, Enrique F.; DeCherney, Alan H.; Segars, James H.; Armstrong, Alicia Y.

    2011-01-01

    Objective To define whether anti-mullerian hormone may be a marker of acute cyclophosphamide-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix. Design Controlled, experimental study. Setting Research laboratory in a federal research facility. Animals Balb/c female mice (6 weeks old). Interventions Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of cyclophosphamide or saline control on day 9. Main Outcome Measure(s) Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels. Results Ovaries in mice pre-treated with cetrorelix had significantly more PMF and reduced DNA damage compared to those exposed to cyclophosphamide alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups. Conclusions Cetrorelix protected primordial follicles and reduced DNA damage in follicles of mice treated with cyclophosphamide, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix. PMID:21550044

  6. Evaluation of an immunoenzymometric assay (IEMA) using automated system for determination of luteinizing hormone and follicle stimulating hormone.

    PubMed

    Fonseca, E; Mason, M; Galván, R E; Pascoe, D; Ochoa, R; Hernández, M; Zárate, A

    1997-01-01

    It has been proposed that automated systems for immunoenzymometric assay (IEMA) may substitute traditional radioimmunoassay (RIA) for measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood due to the advantage of being more rapid, higher sensitivity, lower cost and not requiring radioactive reagents. The study was designed to evaluate both systems using serum samples to determine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. The automatic system (ES-300) for IEMA utilized two monoclonal antibodies, one of them on the solid phase was the specific extractant for the antigen, and the other was a peroxidase labeled antibody which recognizes a different epitope in the antigen molecule, specifically bound in linear proportion to the antigen concentration. Blood samples were obtained from patients who were treated at the hospital for various clinical problems ("problem group") as well as blood samples from patients in whom FSH and LH concentrations were already known ("high", "medium" and "low" levels) by previous RIA ("control group"). IEMA showed a higher sensitivity, 0.42 and 0.96 mIU/ml for FSH and LH, respectively, whereas RIA was 1.95 mIU/ml for both hormones. Intra- and interassay coefficient of variation were below 10% within the range of 15-150 mIU/ml for FSH and 5-100 mIU/ml for LH; however, the coefficient of variation was 15-25% at lower concentrations of FSH and LH. Accuracy of IEMA was evaluated by recovery percentage, thus when high and medium concentrations of FSH and LH were analyzed the recovery was between 99-104%. On the other hand, the recovery was 110% when low levels of FSH and LH were used. In conclusion, IEMA resulted reliable when FSH and LH concentrations are in the middle and high range; likewise, the detection limit of IEMA was lower than RIA, particularly for FSH. On the bases of these results, IEMA showed several advantages over RIA, but its reliability diminishes when serum

  7. Correlation of protein kinase activation and testosterone production after stimulation of Leydig cells with luteinizing hormone.

    PubMed Central

    Cooke, B A; Lindh, M L; Janszen, F H

    1976-01-01

    The effect of different doses of luteinizing hormone on activation of protein kinases, cyclic AMP and testosterone production was studied in purified rat testis Leydig-cell preparations in the presence of 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). In addition, the nature of the protein kinases present in these cells and other tissues was investigated. The following results were obtained. 1. With all the amounts of luteinizing hormone used (0.1-1000 ng/ml), both activation of protein kinase and stimulation of testosterone production were demonstrated. With the lowest amount of luteinizing hormone (0.1 ng/ml), an 8.4+/-0.9% (S.E.M.,n=6) stimulation of protein kinase activation occurred, increasing to 100% with 1000 ng/ml, compared with 3.2+/-1.0%(S.E.M.,n=7) and 100% stimulation of testosterone production with 0.1 and 100 ng/ml respectively. 2. With amounts of luteinizing hormone up to 1 ng/ml (which gave half-maximal stimulation of testosterone production) no detectable increases in net cyclic AMP production were obtained. With higher amounts of luteinizing hormone, cyclic AMP production increased, but maximal production was not reached with 1000 ng/ml. 3. Two isoenzymic forms of protein kinase were present in Leydig cells and seminiferous tubules; type I was eluted with 0.075 M-and type II with 0.22-0.25 m-NaCl from DEAE-cellulose columns. 4. The protein kinase activity was not affected by the presence of erythrocytes in the Leydig-cell preparation, but varied depending on the type of histone used as substrate (histone F2b greater than mixed greater than histone F1). PMID:189752

  8. Follicle-stimulating Hormone Regulates Pro-apoptotic Protein Bcl-2-interacting Mediator of Cell Death-Extra Long (BimEL)-induced Porcine Granulosa Cell Apoptosis*

    PubMed Central

    Wang, Xian-Long; Wu, Yi; Tan, Lu-Bin; Tian, Zhen; Liu, Jing-Hao; Zhu, De-Sheng; Zeng, Shen-Ming

    2012-01-01

    The pro-apoptotic protein Bim (B-cell lymphoma-2 (Bcl-2)-interacting modulator of cell death) has recently been identified and shown to promote cell death in response to several stimuli. In this report, we investigated the role of Bim in porcine follicular atresia. Initially, Bim cDNA was cloned and characterized from porcine ovarian tissue. Porcine Bim had three alternative splicing variants (Bim-extra long, Bim-long, and Bim-short), all containing the consensus Bcl-2 homology 3 domain. We then found the Bim-extra long (BimEL) protein, the most abundant isoform of Bim, was strongly expressed and co-localized with apoptotic (TUNEL-positive) granulosa cells from porcine atretic follicles. Furthermore, overexpression of BimEL triggered apoptosis in granulosa cells. In primary granulosa cell cultures under basal conditions, we observed that BimEL expression was dampened by treatment with follicle-stimulating hormone (FSH). The role of the PI3K/Akt pathway in the regulation of repression was clarified by the use of the PI3K inhibitor, LY294002, and by transfection with Akt siRNA. Forkhead Box Protein O3a (FoxO3a), a well defined transcriptional activator of Bim, was phosphorylated at Ser-253 and inactivated after FSH stimulation. Also, FSH abolished FoxO3a nuclear accumulation in response to LY294002. Finally, chromatin immunoprecipitation assays demonstrated that FoxO3a directly bound and activated the bim promoter. Taken together, we conclude that BimEL induces porcine granulosa cell apoptosis during follicular atresia, and its expression is regulated by FSH via the PI3K/Akt/FoxO3a pathway. PMID:22235114

  9. Starfish gonadotropic hormone: Relaxin-like gonad-stimulating peptides.

    PubMed

    Mita, Masatoshi

    2016-05-01

    Relaxin-like gonad-stimulating peptide (RGP) of starfish Patiria (= Asterina) pectinifera is the first identified invertebrate gonadotropin to trigger final gamete maturation. Recently, chemical structures of RGP were identified in several species of starfish. Three kinds of RGP molecules are found in the class Asteroidea. The chemical structure of P. pectinifera RGP (PpeRGP) is conserved among starfish of the order Valvatida beyond species. In contrast, the chemical structures of RGP identified in Asterias amurensis and Aphelasterias japonica of the order Forcipulatida are quite different from that of PpeRGP. The chemical structure of RGP in A. amurensis (AamRGP) is exactly the same as that in Asterias rubens (the order Forcipulatida), Astropecten scoparius (the order Paxillosida), Astropecten polyacanthus (the order Paxillosida), and Echinaster luzonicus (the order Spinulosida). The chemical structure of Coscinasterias acutispina RGP (the order Forcipulatida) is consistent with that of A. japonica RGP (AjaRGP). In cross-experiments using P. pectinifera, A. amurensis, and A. japonica ovaries, AamRGP and AjaRGP can induce each species of ovaries. Neither AamRGP nor AjaRGP induce oocyte maturation and ovulation in the ovary of P. pectinifera, although the PpeRGP is active in ovaries of A. amurensis and A. japonica. This suggests that the AamRGP and AjaRGP partly act species specificity. PMID:27102940

  10. Follicular dermographism.

    PubMed

    Shelley, W B; Shelley, E D

    1983-09-01

    Four patients who complained of an inexplicable pruritus of several weeks to several years in duration are presented. General medical studies were unremarkable and the skin was normal except for erythematous papular lesions at sites recently scratched. The skin changes could be reproduced by multiple firm strokes with the broad edge of a tongue blade. The transitory, discrete, follicular, urticarial papules so elicited have been labeled by us as follicular dermographism. It is an entity to be distinguished from cholinergic and aquagenic urticaria. We postulate that follicular dermographism occurs during periods of transient antigenemia. At such times, the frictional force of scratching or the tongue blade test releases antigen from the blood stream to trigger focal urticaria at sites of high density mast cells, namely around the hair follicle. Hydroxyzine is an effective therapy. PMID:6627988

  11. Pubertal development in the male pig: effects of treatment with a long-acting gonadotropin-releasing hormone agonist on plasma luteinizing hormone, follicle stimulating hormone and testosterone.

    PubMed Central

    Trudeau, V L; Meijer, J C; Erkens, J H; van de Wiel, D F; Wensing, C J

    1992-01-01

    The effects of a long-acting gonadotropin-releasing hormone (GnRH) agonist, [D-Trp6]-GnRH (GnRH-A) on developmental profiles of plasma luteinizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T), and pituitary responsiveness to exogenous GnRH were studied in male Dutch Landrace x Large White crossbred pigs from 1 to 30 wk of age. Group 1 control animals (control; n = 12) were injected subcutaneously in the neck with vehicle at 1 and 16 wk of age. Group 2 animals (early treatment; n = 10) were injected with 600 micrograms [D-Trp6]-GnRH at 1 wk and with vehicle at 16 wk. Group 3 animals (late treatment; n = 8) were injected with vehicle and 3 mg GnRH-A at 1 and 16 wk, respectively. Group 4 animals (early plus late treatment; n = 9) were injected at both 1 and 16 wk with GnRH-A. Blood was collected by brachiocephalic puncture at weekly or biweekly intervals, and through brachiocephalic cannulae, to determine longitudinal profiles of LH, FSH and T, and plasma gonadotropin responses to intravenous injection of GnRH (0.1 microgram/kg), respectively. In control animals, LH and FSH declined over the first 5 wk of postnatal life and peaked again at 10-14 wk. Levels of both hormones were basal from 18 to 30 wk. Plasma T was high in the first week, declined progressively over the next few weeks and remained low until 24 wk when a transient increment was noted. The LH and FSH responses to acute GnRH stimulation were similar at 7 and 14 wk and declined significantly at 23 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1534270

  12. Effectiveness of a recombinant human follicle stimulating hormone on the ovarian follicles, peripheral progesterone, estradiol-17β, and pregnancy rate of dairy cows

    PubMed Central

    Ali, Mohamed; Moustafa M., Zeitoun

    2016-01-01

    Aims: This study aimed at elucidating the effects of recombinant human follicle stimulating hormone (r-hFSH) on the ovarian follicular dynamics, progesterone, estradiol-17β profiles, and pregnancy of dairy cows. Materials and Methods: Three groups (G, n=5 cows) of multiparous dairy cows were used. G1 (C) control cows were given controlled internal drug release (CIDR) and prostaglandin F2α; G2 (L) cows were given low dose (525 IU and G3 (H) cows were given high dose (1800 IU) of r-hFSH on twice daily basis at the last 3 days before CIDR removal. All cows were ultrasonically scanned for follicular growth and dynamics, and blood samples were collected every other day for two consecutive estrus cycles for the determination of estradiol-17β and progesterone. Results: Estrus was observed in all C and L but not in H cows. Dominant follicle was bigger in L compared to C and H cows. Dominant follicle in C (16.00±2.5 mm) and L cows (17.40±2.3 mm) disappeared at 72 h after CIDR removal. However, in H cows, no ovulation has occurred during 7 days post-CIDR removal. Progesterone was not different (p>0.10) among groups, whereas estradiol-17β revealed significant (p<0.01) reduction in H (15.96±2.5 pg/ml) cows compared to C (112.26±26.1 pg/ml) and L (97.49±15.9 pg/ml) cows. Pregnancy rate was higher in L cows (60%) compared with C cows (20%). However, H cows were not artificially inseminated due to non-ovulation. Only a cow of C group has calved one calf, however, 2 of the L cows gave birth of twins and a cow gave single calf. Conclusion: Administration of a low dose (525 IU) of r-hFSH resulted in an optimal size of dominant follicle, normal values of progesterone and estradiol-17β, and 40% twinning rate, howeverusing 1800 IU of r-hFSH, have adverse effects on ovarian follicular dynamics and hormonal profiles with non-pregnancy of dairy cows raised under hot climate. PMID:27536029

  13. Anti-Mullerian hormone (AMH) concentration in follicular fluid and mRNA expression of AMH receptor type II and LH receptor in granulosa cells as predictive markers of good buffalo (Bubalus bubalis) donors.

    PubMed

    Liang, Aixin; Salzano, Angela; D'Esposito, Maurizio; Comin, Antonella; Montillo, Marta; Yang, Liguo; Campanile, Giuseppe; Gasparrini, Bianca

    2016-09-01

    High individual variability in follicular recruitment and hence in the number of embryos produced is a major factor limiting the application of reproductive technologies in buffalo. Therefore, the identification of reliable markers to select embryo donors is critical to enroll buffaloes in embryo production programs. Better understanding of factors involved in follicular growth is also necessary to improve the response to superovulation in this species. The aim of this work was thus to determine the anti-Mullerian hormone (AMH) concentration in follicular fluid (FF) recovered from different size follicles and evaluate the mRNA expression profiles of development-related (AMHR2, CYP19A1, FSHR, and LHR) and apoptosis-related genes (TP53INP1 and CASP3) in the corresponding granulosa cells (GCs) in buffalo. Another objective was to evaluate whether the AMH concentration in FF and gene expression of GCs is associated with the antral follicular count. Ovaries were collected at the slaughterhouse, and all follicles were counted and classified as small (3-5 mm), medium (5-8 mm), and large (>8 mm). Follicular fluid was recovered for AMH determination, and the mRNA expression of AMHR2, FSHR, LHR, CYP19A1, TP53INP1, and CASP3 was analyzed in GCs. The AMH concentration in FF decreased (P < 0.01) at increasing follicular diameter. The mRNA expression of AMHR2 and FSHR was higher (P < 0.05) in small follicles, whereas that of LHR and CYP19A1 was higher (P < 0.05) in large follicles. The intrafollicular AMH concentration was positively correlated with the antral follicular count (r = 0.31; P < 0.05). Interestingly, good donors (≥12 follicles) had a higher (P < 0.05) concentration of AMH and AMHR2 levels in small follicles and higher (P < 0.05) LHR levels in large follicles than bad donors (<12 follicles). These results suggest a potential use of AMH to select buffalo donors to enroll in embryo production programs, laying the basis for further investigations

  14. Sex-specific regulation of follicle-stimulating hormone secretion by synaptotagmin 9

    PubMed Central

    Roper, Lindsey K.; Briguglio, Joseph S.; Evans, Chantell S.; Jackson, Meyer B.; Chapman, Edwin R.

    2015-01-01

    The anterior pituitary releases six different hormones that control virtually all aspects of vertebrate physiology, yet the molecular mechanisms underlying their Ca2+-triggered release remain unknown. A subset of the synaptotagmin (syt) family of proteins serve as Ca2+ sensors for exocytosis in neurons and neuroendocrine cells, and are thus likely to regulate pituitary hormone secretion. Here we show that numerous syt isoforms are highly expressed in the pituitary gland in a lobe, and sex-specific manner. We further investigated a Ca2+-activated isoform, syt-9, and found that it is expressed in a subpopulation of anterior pituitary cells, the gonadotropes. Follicle-stimulating hormone (FSH) and syt-9 are highly co-localized in female, but not male, mice. Loss of syt-9 results in diminished basal and stimulated FSH secretion only in females, resulting in alterations in the oestrus cycle. This work uncovers a new function for syt-9 and reveals a novel sex difference in reproductive hormone secretion. PMID:26482442

  15. Oestradiol stimulates tyrosine phosphorylation and hormone binding activity of its own receptor in a cell-free system.

    PubMed Central

    Auricchio, F; Migliaccio, A; Di Domenico, M; Nola, E

    1987-01-01

    Recent experiments have shown that calf uterus oestrogen receptor exists in a tyrosine-phosphorylated hormone binding form and in non-phosphorylated, non-hormone binding form. We report here that physiological concentrations of oestradiol in complex with the receptor stimulate the calf uterus receptor kinase that converts the non-hormone binding receptor into hormone binding receptor through phosphorylation of the receptor on tyrosine. The activity of this enzyme has been followed by reactivation of hormone binding sites and phosphorylation on tyrosine of calf uterus phosphatase-inactivated receptor. Phosphorylation of the receptor has been demonstrated by interaction of kinase 32P-phosphorylated proteins with anti-receptor antibody followed either by sucrose gradient centrifugation or SDS-PAGE of the immunoprecipitated proteins. Hormone stimulation of the kinase is inhibited by receptor occupancy of the anti-oestrogen tamoxifen. Oestradiol-receptor complex increases the affinity of the kinase for the dephosphorylated receptor. Findings of this report are consistent with the observation that several protein tyrosine kinases that are associated with peptide hormone receptors are stimulated by the binding of the hormone to the receptor. This is the first report on the activation of a tyrosine kinase by a steroid hormone. The finding that hormones can regulate their own receptor binding activity through a tyrosine kinase is also new. Images Fig. 2. Fig. 4. Fig. 5. PMID:3691476

  16. Thyroid-stimulating hormone (TSH): measurement of intracellular, secreted, and circulating hormone in Xenopus laevis and Xenopus tropicalis.

    PubMed

    Korte, Joseph J; Sternberg, Robin M; Serrano, Jose A; Thoemke, Kara R; Moen, Scott M; Lillegard, Kathryn E; Hornung, Michael W; Tietge, Joseph E; Degitz, Sigmund J

    2011-05-01

    Thyroid-stimulating hormone (TSH) is an important regulator of the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis. To evaluate the role of this hormone on developing tadpoles, immunologically-based Western blots and sandwich ELISAs were developed for measuring intracellular (within pituitaries), secreted (ex vivo pituitary culture), and circulating (serum) amounts. Despite the small size of the tadpoles, these methods were able to easily measure intracellular and secreted TSH, and circulating TSH was measurable in situations where high levels were induced. The method was validated after obtaining a highly purified and enriched TSH sample using anti-TSH-β antibodies conjugated to magnetic beads. Subsequent mass-spectrometric analysis of the bands from SDS-PAGE and Western procedures identified the presence of amino acid sequences corresponding to TSH subunits. The purified sample was also used to prepare standard curves for quantitative analysis. The Western and ELISA methods had limits of detection in the low nanogram range. While the majority of the developmental work for these methods was done with X. laevis, the methods also detected TSH in Xenopus tropicalis. To our knowledge this is the first report of a specific detection method for TSH in these species, and the first to measure circulating TSH in amphibians. Examples of the utility of the methods include measuring a gradual increase in pituitary TSH at key stages of development, peaking at stages 58-62; the suppression of TSH secretion from cultured pituitaries in the presence of thyroid hormone (T4); and increases in serum TSH following thyroidectomy. PMID:21354158

  17. Differential thermal stability of human, bovine and ovine Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) quaternary structures.

    PubMed

    Haj Hassan, Maya; Cahoreau, Claire; Jégot, Gwenhael; Jouanny, Camille; Mariot, Julie; Lecompte, François; Klett, Danièle; Combarnous, Yves

    2015-02-01

    Quaternary structure of human, bovine and ovine Follicle-Stimulating Hormones (hFSH, bFSH and oFSH) and Luteinizing Hormone was assessed in sandwich ELISAs using monoclonal anti-oFSHβ or anti-oLHβ antibodies, respectively, for capture and a biotinylated anti-hFSHα (α4 epitope) for detection. Neither free subunit gave any signal in this assay so that it was possible to measure the residual heterodimeric fraction after thermal treatment of the gonadotropins under study. The hormones were subjected to 5-min heating between 37 and 90 °C before rapid cooling in melting ice before ELISA. The data show half-dissociation of natural and recombinant human and ovine FSH preparations between 68 and 74 °C whereas bovine FSH preparations exhibited lower stability in these conditions with half-dissociation between 61 and 64 °C. Moreover, whereas all human and bovine as well as most ovine FSH preparations were fully dissociated at temperatures above 80 °C, one natural oFSH and one recombinant hLH preparations contained an important fraction that resisted dissociation even at 93 °C and retained in vitro bioactivity. This suggests the existence of gonadotropin αβ heterodimer with covalently linked subunits. Similarly, about 20% of the recombinant hLH preparation was also found withstand heat denaturation and also probably to have cross-linked subunits. The origin and chemical nature of these inter-subunit bonds remain to be determined. PMID:24732063

  18. Rapid and transitory stimulation of 3-O-methylglucose transport by growth hormone

    SciTech Connect

    Carter-Su, C.; Rozsa, F.W.; Wang, Xueyan; Stubbart, J.R. )

    1988-11-01

    The regulation of hexose transport by growth hormone (GH) was investigated using isolated rat adipocytes. GH caused a rapid (<3 min) rise in rates of 3-O-methylglucose transport that reached a maximum of two to six times the basal rates in 10-30 min. The stimulation of transport was transitory, and rates of transport started to decline 15-30 min after GH was added. Transport stimulation required a period of preincubation; no stimulation was observed in freshly isolated cells. GH stimulated hexose transport between 100 and 5,000 ng/ml, with a 50% effective dose between 200 and 300 ng/ml. Depletion of cellular ATP by 2,4-dinitrophenol blocked the ability of GH to stimulate transport but not the decline of transport rates following stimulation by GH. In contrast, an inhibitor of RNA synthesis, actinomycin D, had no effect on either the initial stimulation by GH or the initial subsequent decline of transport when added simultaneously or 15 min prior to GH. Actinomycin D did, however, cause a second rise in hexose transport at {approximately}120 min that was blocked by 2,4-dinitrophenol. These results suggest that changes in glucose transport contribute to the effects of GH on carbohydrate and lipid metabolism in adipose tissue. These changes are rapid, of substantial magnitude, and of a complex nature, suggesting that regulation of glucose transport by GH most likely involves multiple mechanisms.

  19. Growth hormone, luteinizing hormone, and follicle-stimulating hormone regulation by neuropeptide Y in both sexes of the cichlid fish, Cichlasoma dimerus.

    PubMed

    Di Yorio, M P; Delgadin, T H; Pérez Sirkin, D I; Vissio, P G

    2015-08-01

    Neuropeptide Y (NPY) is considered the most potent orexigenic peptide, increasing before meal time and during fasting. In teleost, most studies on NPY action upon growth hormone (GH) and luteinizing hormone (LH) were conducted in females or group of animals without sex discrimination. The aim of this study was to evaluate whether NPY modulates the expression and release of GH and gonadotropins in both sexes of Cichlasoma dimerus. By double-label immunofluorescence, we first determined the association between NPY fibers and pituitary cells. In addition, we performed in vitro studies to evaluate the effect of NPY on GH and gonadotropins expression by real-time PCR, and release by Western blot, in males and females separately. Contacts between NPY fibers and GH and follicle-stimulating hormone (FSH)-producing cells were detected, indicating possible functional relationships. We observed an increase in GH release in the culture medium at 2 nM for males (p = 0.043) and 20 nM for females (p = 0.028). Pituitary FSH release was stimulated at 20 nM (p = 0.026) and 200 nM (p = 0.033) for males and females, respectively. Finally, NPY only increased β-LH mRNA expression at 20 nM in females (p = 0.028) and its release at 2 nM (p = 0.049) and 200 nM for males (p = 0.005) and 200 nM for females (p = 0.018). In conclusion, NPY acts as a GH-, LH- and FSH-releasing factor, in a dose- and sex-dependent way. PMID:25869217

  20. Effects of Full-Length Kisspeptin Administration on Follicular Development in Japanese Black Beef Cows

    PubMed Central

    NANIWA, Yousuke; NAKATSUKASA, Keisuke; SETSUDA, Shohei; OISHI, Shinya; FUJII, Nobutaka; MATSUDA, Fuko; UENOYAMA, Yoshihisa; TSUKAMURA, Hiroko; MAEDA, Kei-ichiro; OHKURA, Satoshi

    2013-01-01

    Abstract Kisspeptin is a key molecule that stimulates gonadotropin secretion via release of gonadotropin-releasing hormone (GnRH). In the present study, our aim was to investigate whether kisspeptin has stimulatory effects on follicular development via GnRH/gonadotropin secretion in cows. Japanese Black beef cows were intravenously injected with full-length bovine kisspeptin [Kp-53 (0.2 or 2 nmol/kg)] or vehicle 5 days after they exhibited standing estrus (Day 0). In cows injected with Kp-53 at 2 nmol/kg, the follicular sizes of the first dominant follicles increased on Day 6 and thereafter. Ovulation of the first dominant follicle occurred in 1 out of 4 cows treated with Kp-53 at 2 nmol/kg. Injection of Kp-53 at 2 nmol/kg increased the concentration of plasma luteinizing hormone (LH) but not follicle-stimulating hormone, over a 4-h period following injection in all cows. The present study suggests that administration of full-length kisspeptin causes LH secretion, which is sustained for a few hours, and it is capable of stimulating follicular development and/or ovulation. PMID:24107742

  1. Granulocyte colony-stimulating factor: A relation between serum and follicular fluid levels and in-vitro fertilization outcome in patients with polycystic ovary syndrome.

    PubMed

    Kahyaoglu, Inci; Yılmaz, Nafiye; Timur, Hakan; Inal, Hasan Ali; Erkaya, Salim

    2015-07-01

    Evidence is accumulating in the literature about the potential role of serum and follicular fluid (FF) granulocyte colony-stimulating factor (G-CSF) as a non-invasive biomarker of oocyte competence and embryo selection in in-vitro fertilization (IVF) cycles. In this study, we aimed to evaluate the effect of serum and FF G-CSF levels on IVF outcome in non-hyperandrogenic, non-obese patients with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS (Group I), and 22 patients with the etiology of male factor infertility (Group II) undergoing IVF treatment were included. Demographic features, controlled ovarian stimulation parameters, neutrophil count (NC), neutrophil/leukocyte (N/L) ratio, serum and FF G-CSF levels of the two groups were compared. Serum E2 level on the day of hCG (2982.5±171.4 vs. 2279.0±207.2 pg/mL), total number of retrieved oocytes (14.7±0.9 vs. 11.5±1.3) and mature oocytes (11.6±0.8 vs. 9.1±1.1) were significantly higher in group I when compared to group II (p<0.05). On the day of oocyte retrieval, both the mean serum (54.8±1.7 vs. 48.1±0.9 pg/mL) and FF G-CSF levels (48.8±1.4 vs. 44.1±0.5 pg/mL), NC (4.4±0.2×10(3) vs. 3.6±0.3×10(3)/μL) and N/L ratio (63.6±1.4 vs. 56.1±1.7) in group I were found to be significantly higher than group II ((p<0.05). Despite the increased levels of G-CSF both in the serum and follicular microenvironment in patients with PCOS, a relation between G-CSF and good ovarian response or clinical pregnancy rates could not be demonstrated in this study. PMID:25258001

  2. The influence of nutrition on the insulin-like growth factor system and the concentrations of growth hormone, glucose, insulin, gonadotropins and progesterone in ovarian follicular fluid and plasma from adult female horses (Equus caballus)

    PubMed Central

    2014-01-01

    Background Feed intake affects the GH-IGF system and may be a key factor in determining the ovarian follicular growth rate. In fat mares, the plasma IGF-1 concentration is high with low GH and a quick follicular growth rate, in contrast to values observed in thin mares. Nothing is known regarding the long-term effects of differential feed intake on the IGF system. The objective of this experiment was to quantify IGFs, IGFBPs, GH, glucose, insulin, gonadotropin and progesterone (P4) in blood and in preovulatory follicular fluid (FF) in relation to feeding levels in mares. Methods Three years prior to the experiment, Welsh Pony mares were assigned to a restricted diet group (R, n = 10) or a well-fed group (WF, n = 9). All mares were in good health and exhibited differences in body weight and subcutaneous fat thickness. Follicular development was scanned daily and plasma was also collected daily. Preovulatory FF was collected by ultrasound-guided follicular aspiration. Hormone levels were assayed in FF and plasma with a validated RIA. Results According to scans, the total number of follicles in group R was 53% lower than group WF. Insulin and IGF-1 concentrations were higher in WF than in R mares. GH and IGF-2 concentrations were lower in plasma from WF mares than from R mares, but the difference was not significant in FF. The IGFBP-2/IGFBP-3 ratio in FF was not affected by feeding but was dramatically increased in R mare plasma. No difference in gonadotropin concentration was found with the exception of FSH, which was higher in the plasma of R mares. On the day of puncture, P4 concentrations were not affected by feeding but were higher in preovulatory FF than in plasma. Conclusions The bioavailability of IGF-1 or IGF-2, represented by the IGFBP2/IGFBP3 ratio, is modified by feed intake in plasma but not in FF. These differences partially explain the variability in follicular growth observed between well-fed mares and mares on restricted diets. PMID:25078409

  3. Effect of addition of human follicular fluid on progesterone secretion by cultured sheep granulosa cells.

    PubMed

    Kumari, G L; Vohra, S; Raghavan, V

    1982-10-01

    The effect of addition of human follicular fluid to cultures of granulosa cells of large sheep follicles (4-6 mm in diameter) on basal and LH-stimulated progesterone secretion was investigated. Both luteinization and progesterone secretion were inhibited by addition of 10% (w/v) charcoal-treated follicular fluid from medium (2-6 mm) and large (7-16 mm) follicles which had low concentrations of estradiol-17 beta, progesterone and LH. In comparison, the fluid from large follicles, having high levels of the same hormones, stimulated both the parameters, and addition of LH along with the fluid had no further effect. Fluid collected from cystic follicles appeared to be stimulatory which also had elevated levels of estradiol-17 beta and progesterone. These findings indicate the presence of both the inhibitors and stimulators of luteinization in human follicular fluid. The effectiveness of any of them either to inhibit or stimulate luteinization probably will depend upon the composition of the follicular fluid and the stage of maturation of the follicles from which it was collected. PMID:6218983

  4. Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet.

    PubMed

    Egan, J J; Greenberg, A S; Chang, M K; Wek, S A; Moos, M C; Londos, C

    1992-09-15

    Hormone-sensitive lipase activity (HSL), which is found in the supernatant of centrifuged homogenates of lipolytically quiet isolated rat adipocytes, was greatly reduced in or absent from the supernatant of lipolytically stimulated cells. The lipase was purified 100- to 250-fold from the supernatant of lipolytically quiet cells to 10-20% purity by a single passage over phenyl-Sepharose resin with high (greater than 70%) activity yields. Western blotting of adipocyte homogenate fractions with polyclonal antiserum raised against HSL showed that the enzyme shifted quantitatively from the supernatant of control cells to the floating "fat cake" of lipolytically stimulated cells. A similar shift to the fat cake was observed when cells were disrupted by hypotonic lysis and centrifugation rather than by homogenization. We propose that upon lipolytic activation of adipocytes and phosphorylation of HSL by cAMP-dependent protein kinase, the critical event is not an increase in catalytic activity (i.e., turnover number) but a translocation of the lipase to its substrate at the surface of the lipid storage droplet. PMID:1528859

  5. Host stress hormone norepinephrine stimulates pneumococcal growth, biofilm formation and virulence gene expression

    PubMed Central

    2014-01-01

    Background Host signals are being shown to have a major impact on the bacterial phenotype. One of them is the endogenously produced catecholamine stress hormones, which are also used therapeutically as inotropes. Recent work form our laboratories have found that stress hormones can markedly increase bacterial growth and virulence. This report reveals that Streptococcus pneumoniae, a commensal that can also be a major cause of community acquired and nosocomial pneumonia, is highly inotrope responsive. Therapeutic levels of the stress hormone norepinephrine increased pneumococcal growth via a mechanism involving provision of iron from serum-transferrin and inotrope uptake, as well as enhancing expression of key genes in central metabolism and virulence. Collectively, our data suggests that Streptococcus pneumoniae recognises host stress as an environmental cue to initiate growth and pathogenic processes. Results Effects of a clinically attainable concentration of norepinephrine on S. pneumoniae pathogenicity were explored using in vitro growth and virulence assays, and RT-PCR gene expression profiling of genes involved in metabolism and virulence. We found that norepinephrine was a potent stimulator of growth, via a mechanism involving norepinephrine-delivery of transferrin-iron and internalisation of the inotrope. Stress hormone exposure also markedly increased biofilm formation. Importantly, gene profiling showed that norepinephrine significantly enhanced expression of genes involved in central metabolism and host colonisation. Analysis of the response of the pneumococcal pspA and pspC mutants to the stress hormone showed them to have a central involvement in the catecholamine response mechanism. Conclusions Collectively, our evidence suggests that the pneumococcus has mechanisms to recognise and process host stress hormones to augment its virulence properties. The ability to respond to host stress signals may be important for the pneumococcal transition from

  6. Molecular characterization of the Chinese alligator follicle-stimulating hormone β subunit (FSHβ) and its expression during the female reproductive cycle.

    PubMed

    Zhang, Rui; Zhang, Shengzhou; Zhu, Xue; Zhou, Yongkang; Wu, Xiaobing

    2015-05-01

    The Chinese alligator Alligator sinensis is an endangered species endemic to China, it has a highly specialized reproductive pattern with low fecundity. Up to date, little is known about the regulation of its female reproductive cycle. Follicle-stimulating hormone (FSH), a glycoprotein hormone, plays a key role in stimulating and regulating ovarian follicular development and egg production. In this study, the complete FSHβ cDNA from the ovary of the Chinese alligator was obtained for the first time, it consists of 843-bp nucleotides, including 120-bp nucleotides of the 5'-untranslated region (UTR), 396-bp of the open reading frame, and 3'-UTR of 327-bp nucleotides. It encodes a 131-amino acid precursor molecule of FSHβ with a signal peptide of 18 amino acids followed by a mature protein of 113 amino acids. Its deduced amino acid sequence shares high identities with the American alligator (100%) and birds (89-92%). Phylogenetic tree analysis of the FSHβ amino acid sequence indicated that alligators cluster into the bird branch. Tissue distribution analyses indicated that FSHβ mRNA is expressed in ovary, intestine and liver with the highest level in the ovary, while not in stomach, pancreas, heart, thymus and thyroid. Expression of FSHβ in ovary increases in May (breeding prophase) and peaks in July (breeding period), it is maintained at high levels through September, then decreases significantly in November (post-reproductive period) and remains relatively low from January to March (hibernating period). These temporal changes of FSHβ expression implicated that it might play an important role in promoting ovarian development during the female reproductive cycle. PMID:25626184

  7. Taste matters - effects of bypassing oral stimulation on hormone and appetite responses.

    PubMed

    Spetter, Maartje S; Mars, Monica; Viergever, Max A; de Graaf, Cees; Smeets, Paul A M

    2014-10-01

    The interaction between oral and gastric signals is an important part of food intake regulation. Previous studies suggest that bypassing oral stimulation diminishes the suppression of hunger and increases gastric emptying rate. However, the role of appetite hormones, like cholecystokinin-8 and ghrelin, in this process is still unclear. Our objective was to determine the contributions of gastric and oral stimulation to subsequent appetite and hormone responses and their effect on ad libitum intake. Fourteen healthy male subjects (age 24.6±3.8y, BMI 22.3±1.6kg/m(2)) completed a randomized, single-blinded, cross-over experiment with 3 treatment-sessions: 1) Stomach distention: naso-gastric infusion of 500mL/0kJ water, 2) Stomach distention with caloric content: naso-gastric infusion of 500mL/1770kJ chocolate milk, and 3) Stomach distention with caloric content and oral exposure: oral administration of 500mL/1770kJ chocolate milk. Changes in appetite ratings and plasma glucose, insulin, cholecystokinin-8, and active and total ghrelin concentrations were measured at fixed time-points up to 30min after infusion or oral administration. Subsequently, subjects consumed an ad libitum buffet meal. Oral administration reduced appetite ratings more than both naso-gastric infusions (P<0.0001). Gastric infusion of a caloric load increased insulin and cholecystokinin-8 and decreased total ghrelin concentrations more than ingestion (all P<0.0001). No differences in active ghrelin response were observed between conditions. Ad libitum intake did not differ between oral and gastric administration of chocolate milk (P>0.05). Thus, gastric infusion of nutrients induces greater appetite hormone responses than ingestion does. These data provide novel and additional evidence that bypassing oral stimulation not only affects the appetite profile but also increases anorexigenic hormone responses, probably driven in part by faster gastric emptying. This confirms the idea that learned

  8. [THE EFFECT OF HORMONAL STIMULATION OF STERLET (ACIPENSER RUTHENUS L.) ON STEROID LEVELS IN TISSUE INCUBATES].

    PubMed

    Bayunova, L V

    2016-01-01

    Sex steroids and corticol levels in Leibovitz's L-15 media samples after incubation of intact female and male sterlet (Acipenser rhutenus L.) tissue fragments and those if fishes treated with a superactive analogue of mammalian luteinising hormone-releasing hormone (LH-RH-A) were compared. 17,20β,21-trihydroxy-4-pregnen-3-one (20βS) levels were significantly higher in the media samples after incubation of ovarian follicles taken from females 5 h after treatment with LH-RH-A in comparison with 20βS levels in intact female samples. 20βS levels also increased after 1 μM progesterone (P4) adding to the media before incubation of ovarian follicles. Cortisol and testosterone levels in the media samples demonstrated the same tendency. Significant elevation of cortisol levels was observed in the blood serum samples of females 5 h after LH-RH-A treatment. The androgens (testosterone and 11-ketotestosterone) levels after incubation of testicular and liver fragments were high in the media samples in males who had high serum levels of these androgens before hormonal stimulation. Sex steroids and cortisol production was stimulated by P4 adding to the media before incubation of gonad fragments. 20βS media levels increased after P4 adding before incubation of liver fragments. PMID:27220236

  9. Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease

    PubMed Central

    Onori, Paolo; Mancinelli, Romina; Franchitto, Antonio; Carpino, Guido; Renzi, Anastasia; Brozzetti, Stefania; Venter, Julie; Francis, Heather; Glaser, Shannon; Jefferson, Douglas M.; Alpini, Gianfranco; Gaudio, Eugenio

    2014-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle-stimulating hormone (FSH) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation (BDL). Aims To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models. Methods Evaluation of FSH receptor (FSHR), FSH, phospho-extracellular-regulated kinase (pERK) and c-myc expression in liver fragments from normal patients and patients with ADPKD. In vitro, we studied proliferating cell nuclear antigen (PCNA) and cAMP levels in a human immortalized, non-malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD (LCDE) with or without transient silencing of the FSH gene. Results Follicle-stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p-ERK and c-myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway. Conclusion These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD. PMID:23617956

  10. Effects of external radiation therapy for cancer of the prostate on the serum concentrations of testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin

    SciTech Connect

    Tomic, R.; Bergman, B.; Damber, J.E.; Littbrand, B.; Loefroth, P.O.

    1983-08-01

    Testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin were analyzed in serum from 31 patients with carcinoma of the prostate treated primarily with megavoltage radiation therapy. The total tumor dose varied between 58 and 71 gray (mean 63.5 gray). Absorbed doses to the testes were measured at approximately 1 to more than 10 gray. We investigated retrospectively 17 patients 3 to 60 months (mean 20 months) after therapy and found significantly lower serum testosterone concentrations and significantly higher luteinizing and follicle-stimulating hormone concentrations than in age-matched controls. Of the patients, 14 were followed before and after radiation treatment. Testosterone concentrations were reduced significantly 1 week as well as 3 months after treatment but pre-treatment values were found on analysis 6 and 12 months after treatment. The values for luteinizing and follicle-stimulating hormones were significantly higher 3, 6 and 12 months after radiation treatment compared to pre-treatment values. The follicle-stimulating hormone value already increased after 1 week. The greatest observed testosterone alteration occurred 1 week after treatment in patients who received more than 10 gray over the gonads. The use of lead shields protecting the testes reduced the dose absorbed to the gonads by approximately 50 percent.

  11. Cholesterol side-chain cleavage cytochrome P450 and 3beta-hydroxysteroid dehydrogenase expression and the concentrations of steroid hormones in the follicular fluids of different phenotypes of healthy and atretic bovine ovarian follicles.

    PubMed

    Irving-Rodgers, Helen F; Krupa, Malgorzata; Rodgers, Raymond J

    2003-12-01

    Bovine ovarian antral follicles exhibit either one or the other of two patterns of granulosa cell death in atresia. Death can commence either from the antrum and progress toward the basal lamina (antral atresia) or the converse (basal atresia). In basal atresia, the remaining live antrally situated cells appeared to continue maturing. Beyond that, little is known about these distinct patterns of atresia. Healthy (nonatretic) follicles also exhibit either one or the other of two patterns of granulosa cell shape, follicular basal lamina ultrastructure or location of younger cells within the membrana granulosa. To examine these different phenotypes, the expression of the steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (SCC) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells and concentrations of steroid hormones in follicular fluid were measured in individual histologically classified bovine antral follicles. Healthy follicles first expressed SCC and 3beta-HSD in granulosa cells only when the follicles reached an approximate threshold of 10 mm in diameter. The pattern of expression in antral atretic follicles was the same as healthy follicles. Basal atretic follicles were all <5 mm. In these, the surviving antral granulosa cells expressed SCC and 3beta-HSD. In examining follicles of 3-5 mm, basal atretic follicles were found to have substantially elevated progesterone (P < 0.001) and decreased androstenedione and testosterone compared to healthy and antral atretic follicles. Estradiol was highest in the large healthy follicles, lower in the small healthy follicles, lower still in the antral atretic follicles, and lowest in the basal atretic follicles. Our findings have two major implications. First, the traditional method of identifying atretic follicles by measurement of steroid hormone concentrations may be less valid with small bovine follicles. Second, features of the two forms of follicular atresia are so different as to

  12. The transcriptome of follicular cells: biological insights and clinical implications for the treatment of infertility

    PubMed Central

    Fragouli, Elpida; Lalioti, Maria D.; Wells, Dagan

    2014-01-01

    , embryo morphology and the establishment of a pregnancy. However, there is a general lack of uniformity concerning groups of gene biomarkers among different studies. CONCLUSIONS Extensive investigation of genes and proteins of granulosa and CCs has provided a detailed insight into the follicular microenvironment surrounding oocytes. It was evident from the data reviewed that the gene expression of follicular cells influences and is influenced by the oocyte, affecting factors such as maturity, chromosomal constitution, viability and competence. However, a general lack of overlap among genes identified as potentially useful biomarkers suggests that the transcriptome of follicular cells could be affected by multiple intrinsic factors, having to do with the patient and possibly the aetiology of infertility, as well as extrinsic factors, such as hormonal stimulation. Further work is required in order to establish a universally applicable, non-invasive test for the determination of oocyte competence based upon follicular cell assessment. PMID:24082041

  13. Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

    PubMed Central

    Davies, Terry F; Latif, Rauf

    2015-01-01

    Introduction The thyroid-stimulating hormone receptor (TSHR) is the essential molecule for thyroid growth and thyroid hormone production. Since it is also a key autoantigen in Graves’ disease and is involved in thyroid cancer pathophysiology, the targeting of the TSHR offers a logical model for disease control. Areas covered We review the structure and function of the TSHR and the progress in both small molecule ligands and TSHR antibodies for their therapeutic potential. Expert opinion Stabilization of a preferential conformation for the TSHR by allosteric ligands and TSHR antibodies with selective modulation of the signaling pathways is now possible. These tools may be the next generation of therapeutics for controlling the pathophysiological consequences mediated by the effects of the TSHR in the thyroid and other extrathyroidal tissues. PMID:25768836

  14. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    PubMed Central

    Jansen, S. W.; Akintola, A. A.; Roelfsema, F.; van der Spoel, E.; Cobbaert, C. M.; Ballieux, B. E.; Egri, P.; Kvarta-Papp, Z.; Gereben, B.; Fekete, C.; Slagboom, P. E.; van der Grond, J.; Demeneix, B. A.; Pijl, H.; Westendorp, R. G. J.; van Heemst, D.

    2015-01-01

    Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism. PMID:26089239

  15. Hormonal characteristics of the human menstrual cycle throughout reproductive life.

    PubMed

    Sherman, B M; Korenman, S G

    1975-04-01

    The changes in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FHS), estradiol, and progesterone that occur both early and late in reproductive life were characterized and compared with findings in young, normal women and in patients with certain menstrual disorders. A total of 50 complete menstrual cycles in 37 were examined. Five distinct patterns of hormonal regulation were found, three of which are reported here: (a) A long follicular phase and delayed follicular maturation in young women with long, unpredictable intermenstrual intervals from menarche; (b) a short follicular phase with increasing age and in short cycles in perimenopausal women; and (c) true anovulatory vaginal bleeding in long cycles in perimenopausal women. The short cycles before and during the menopausal transition were found to have lower E2 levels and high FSH concentrations throughout, while LH remained in the normal range. During long cycles in perimenopausal women, concentrations of LH and FSH were in the menopausal range. However, follicular maturation was observed months after high levels of gonadotropins were attained. These studies permit the characterization of the menstrual history of the normal woman in terms of the hormonal changes that occur and provide a basis for the definition of several disorders of follicular maturation. PMID:1120778

  16. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  17. Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

    PubMed

    Goh, H H; Chew, P C; Karim, S M; Ratnam, S S

    1980-02-01

    Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH. PMID:6772356

  18. A rapid solid-phase radioimmunoassay for human plasma follicle-stimulating hormone.

    PubMed

    Lovesey, A C

    1980-01-01

    The measurement of plasma levels of human follicle-stimulating hormone (FSH) has proved to be of value for the study of the hypothalamic-hypophyseal-gonadal axis, greatly facilitating the diagnosis and mangement of problems relating to the menopause and infertility. In the present work a solid-phase radioimmunoassay for human FSH has been developed. This system is characterised by high precision, is economical, and is considerably faster to operate than conventional double antibody systems used in the hospital assay service. Reference values for plasma FSH in various endocrine states are recorded and discussed. PMID:6769381

  19. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  20. Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

    PubMed

    Veldhuis, J D; Evans, W S; Rogol, A D; Kolp, L; Thorner, M O; Stumpf, P

    1986-06-01

    We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time-dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease. PMID:3086382

  1. Frequency-Dependent Regulation of Follicle-Stimulating Hormone β by Pulsatile Gonadotropin-Releasing Hormone Is Mediated by Functional Antagonism of bZIP Transcription Factors ▿

    PubMed Central

    Ciccone, Nick A.; Xu, Shuyun; Lacza, Charlemagne T.; Carroll, Rona S.; Kaiser, Ursula B.

    2010-01-01

    Oscillatory synthesis and secretion of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), under the control of pulsatile hypothalamic gonadotropin-releasing hormone (GnRH), is essential for normal reproductive development and fertility. The molecular mechanisms by which various patterns of pulsatile GnRH regulate gonadotrope responsiveness remain poorly understood. In contrast to the α and LHβ subunit genes, FSHβ subunit transcription is preferentially stimulated at low rather than high frequencies of pulsatile GnRH. In this study, mutation of a cyclic AMP response element (CRE) within the FSHβ promoter resulted in the loss of preferential GnRH stimulation at low pulse frequencies. We hypothesized that high GnRH pulse frequencies might stimulate a transcriptional repressor(s) to attenuate the action of CRE binding protein (CREB) and show that inducible cAMP early repressor (ICER) fulfills such a role. ICER was not detected under basal conditions, but pulsatile GnRH stimulated ICER to a greater extent at high than at low pulse frequencies. ICER binds to the FSHβ CRE site to reduce CREB occupation and abrogates both maximal GnRH stimulation and GnRH pulse frequency-dependent effects on FSHβ transcription. These data suggest that ICER production antagonizes the stimulatory action of CREB to attenuate FSHβ transcription at high GnRH pulse frequencies, thereby playing a critical role in regulating cyclic reproductive function. PMID:20008557

  2. Transepithelial water flow regulates apical membrane retrieval in antidiuretic hormone-stimulated toad urinary bladder.

    PubMed

    Harris, H W; Wade, J B; Handler, J S

    1986-09-01

    Antidiuretic hormone (ADH) increases the osmotic water permeability (Posm) of toad urinary bladder. This increase is believed to be produced by fusion of intracellular vesicles called aggrephores with the granular cell apical plasma membrane. Aggrephores contain intramembrane particle aggregates postulated to be water channels. ADH-stimulated Posm is decreased by osmotic gradient exposure, which is termed flux inhibition. We studied flux inhibition by exposing ADH-stimulated bladders to various osmotic gradients. Osmotic water flow was initially proportional to the applied osmotic gradient, but Posm decreased with time. Ultrastructural and quantitative studies of endocytosis demonstrate that apical membrane retrieval was a direct function of the transepithelial osmotic gradient. Posm remained unchanged when apical membrane retrieval was blocked by incubation of bladders at 2 degrees C, or under low water-flow conditions. These effects were reversed by increases in temperature or the applied osmotic gradient. We conclude that apical membrane retrieval causes the phenomenon of flux inhibition. PMID:2427542

  3. Gonadotropin releasing hormone (GnRH)--a novel olfactory stimulant in fish.

    PubMed

    Andersen, O; Døving, K B

    1991-08-01

    The aim of this study was to elucidate the putative role of the gonadotropin releasing hormone (GnRH or LHRH) as an olfactory stimulant in fish. We report for the first time extreme sensitivity of the olfactory organ in the rainbow trout (Oncorhynchus mykiss) to GnRH. Recordings of the electroolfactogram (EOG) showed an electrophysiological response to 10(-16) M GnRH four times the amplitude of the response to a fresh water control stimulus. By stimulating the olfactory epithelium with several GnRH analogs and fragments of the decapeptide, the biologically active region of GnRH could be partly elucidated. The response profile of GnRH differed from that of the positive control odorant L-alanine, suggesting that separate receptors or receptor cells are involved. We propose that this potent odorant may act as a reproductive pheromone in fish. PMID:1912479

  4. Molecular analysis of the koala reproductive hormones and their receptors: gonadotrophin-releasing hormone (GnRH), follicle-stimulating hormone β and luteinising hormone β with localisation of GnRH.

    PubMed

    Busby, E R; Soeta, S; Sherwood, N M; Johnston, S D

    2014-12-01

    During evolution, reproductive hormones and their receptors in the brain-pituitary-gonadal axis have been altered by genetic mechanisms. To understand how the neuroendocrine control of reproduction evolved in mammals, it is important to examine marsupials, the closest group to placental mammals. We hypothesised that at least some of the hormones and receptors found in placental mammals would be present in koala, a marsupial. We examined the expression of koala mRNA for the reproductive molecules. Koala cDNAs were cloned from brain for gonadotrophin-releasing hormones (GnRH1 and GnRH2) or from pituitary for GnRH receptors, types I and II, follicle-stimulating hormone (FSH)β and luteinising hormone (LH)β, and from gonads for FSH and LH receptors. Deduced proteins were compared by sequence alignment and phylogenetic analysis with those of other vertebrates. In conclusion, the koala expressed mRNA for these eight putative reproductive molecules, whereas at least one of these molecules is missing in some species in the amniote lineage, including humans. In addition, GnRH1 and 2 are shown by immunohistochemistry to be expressed as proteins in the brain. PMID:25200132

  5. Hormone stimulation of androgen receptor mediates dynamic changes in DNA methylation patterns at regulatory elements

    PubMed Central

    Dhiman, Vineet K.; Attwood, Kristopher; Campbell, Moray J.; Smiraglia, Dominic J.

    2015-01-01

    DNA methylation is an epigenetic modification that contributes to stable gene silencing by interfering with the ability of transcriptional regulators to bind to DNA. Recent findings have revealed that hormone stimulation of certain nuclear receptors induces rapid, dynamic changes in DNA methylation patterns alongside transcriptional responses at a subset of target loci, over time. However, the ability of androgen receptor (AR) to dynamically regulate gene transcription is relatively under-studied and its role in the regulation of DNA methylation patterns remains to be elucidated. Here we demonstrate in normal prostate cells that hormone stimulated AR activity results in dynamic changes in the transcription rate and DNA methylation patterns at the AR target genes, TIPARP and SGK1. Time-resolved chromatin immunoprecipitation experiments on the SGK1 locus reveals dynamic recruitment of AR and RNA Polymerase II, as well as the recruitment of proteins involved in the DNA demethylation process, TET1 and TDG. Furthermore, the presence of DNA methylation at dynamic regions inhibits protein binding and transcriptional activity of SGK1. These findings establish AR activity as a contributing factor to the dynamic regulation of DNA methylation patterns at target genes in prostate biology and infer further complexity involved in nuclear receptor mediation of transcriptional regulation. PMID:26646795

  6. Rapid detection of a point mutation in thyroid-stimulating hormone beta-subunit gene causing congenital isolated thyroid-stimulating hormone deficiency.

    PubMed

    Mori, R; Sawai, T; Kinoshita, E; Baba, T; Matsumoto, T; Yoshimoto, M; Tsuji, Y; Satake, Y; Sawada, K

    1991-12-01

    Previous study showed that congenital isolated TSH deficiency in Japan is resulted exclusively from a G-A transition at nucleotide 145 in exon 2 of the TSH beta-subunit gene. All reported cases were from the inbred in Shikoku Island. We describe here a 10-year-old boy with hereditary TSH deficiency in the same area. The patient was born with a weight of 3,225 g to non-consanguineous parents. Evaluation at age 2 months revealed typical manifestations of cretinism without goiter. Serum T4, T3, and TSH values were 2.53 micrograms/dl, 107 ng/dl, and 0.5 microU/ml, respectively. A TRH stimulation test showed no increment of serum TSH value. Other anterior pituitary hormone levels were all within the normal range. Two oligonucleotide primers T1a and T1b were synthesized according to the sequence data. Amplified 169 bp nucleotides in exon 2 of the TSH beta gene with this primer set were digested with MaeI. Both the phenotypically normal brother and normal controls showed only the 169 bp fragment, whereas the proband showed 140 and 29 bp fragments and both parents showed three fragments; 169, 140, and 29 bp. These results were consistent with the point mutation of TSH beta gene in Japanese patients with congenital isolated TSH deficiency. Our PCR method with MaeI digestion contributes to the rapid detection of the homozygous patient and the heterozygous carrier. PMID:1811097

  7. Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma.

    PubMed

    Wang, Xiaowei; Guo, Tianyao; Peng, Fang; Long, Ying; Mu, Yun; Yang, Haiyan; Ye, Ningrong; Li, Xuejun; Zhan, Xianquan

    2015-06-01

    Nonfunctional pituitary adenoma (NFPA) is highly heterogeneous with different hormone-expressed subtypes in NFPA tissues including follicle-stimulating hormone (FSH) positive, luteinizing hormone-positive, FSH/luteinizing hormone-positive, and negative types. To analyze in-depth the variations in the proteomes among different NFPA subtypes for our long-term goal to clarify molecular mechanisms of NFPA and to detect tumor biomarker for personalized medicine practice, a reference map of proteome of a human FSH-expressed NFPA tissue was described here. 2DE and PDQuest image analysis were used to array each protein. MALDI-TOF PMF and human Swiss-Prot databases with MASCOT search were used to identify each protein. A good 2DE pattern with high level of between-gel reproducibility was attained with an average positional deviation 1.98 ± 0.75 mm in the IEF direction and 1.62 ± 0.68 mm in the SDS-PAGE direction. Approximately 1200 protein spots were 2DE-detected and 192 redundant proteins that were contained in 141 protein spots were PMF-identified, representing 107 nonredundant proteins. Those proteins were located in cytoplasm, nucleus, plasma membrane, extracellular space, and so on, and those functioned in transmembrane receptor, ion channel, transcription/translation regulator, transporter, enzyme, phosphatase, kinase, and so on. Several important pathway networks were characterized from those identified proteins with DAVID and Ingenuity Pathway Analysis systems, including gluconeogenesis and glycolysis, mitochondrial dysfunction, oxidative stress, cell-cycle alteration, MAPKsignaling system, immune response, TP53-signaling, VEGF-signaling, and inflammation signaling pathways. Those resulting data contribute to a functional profile of the proteome of a human FSH-positive NFPA tissue, and will serve as a reference for the heterogeneity analysis of NFPA proteomes. PMID:25809007

  8. Associations between brominated flame retardants in human milk and Thyroid-Stimulating Hormone (TSH) in neonates

    PubMed Central

    Eggesbø, Merete; Thomsen, Cathrine; Jørgensen, Jens V.; Becher, Georg; Odland, Jon Øyvind; Longnecker, Matthew P.

    2011-01-01

    Background Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date. Objectives To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH). Methods We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the “Norwegian Human Milk Study” (HUMIS), 2003–2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers. Results The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of magnitude higher. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs). Conclusions We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed. PMID:21601188

  9. mRNA expression pattern of gonadotropin receptors in bovine follicular cysts.

    PubMed

    Marelli, Belkis E; Diaz, Pablo U; Salvetti, Natalia R; Rey, Florencia; Ortega, Hugo H

    2014-12-01

    Follicular growth and steroidogenesis are dependent on gonadotropin binding to their receptors in granulosa and theca cells of ovarian follicles. The aim of the present study was to evaluate the expression patterns of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHCGR) in ovarian follicular structures from cows with cystic ovarian disease (COD) as compared with those of regularly cycling cows. Relative real-time RT-PCR analysis showed that the expression of FSHR mRNA in granulosa cells was highest in small antral follicles, then decreased significantly as follicles increased in size, and was lowest in cysts. FSHR mRNA was not detected in the theca cells of any follicular category, including cysts. LHCGR mRNA expression in granulosa cells was significantly higher in large antral follicles than in cysts, and not detected in granulosa cells of small and medium antral follicles. In theca cells, the expression level of LHCGR mRNA in medium antral follicles was higher than in small and large antral follicles, whereas that in follicular cysts it was similar to those in small and medium antral follicles, but higher than that in large antral follicles. Our findings provide evidence that there is an altered gonadotropin receptor expression in bovine cystic follicles, and suggest that in conditions characterized by altered ovulation, such as COD, changes in the signaling system of gonadotropins may play a fundamental role in their pathogenesis. PMID:25454493

  10. Identification of gonadotrophin surge-inhibiting factor (GnSIF)/attenuin in human follicular fluid.

    PubMed

    Mroueh, J M; Arbogast, L K; Fowler, P; Templeton, A A; Friedman, C I; Danforth, D R

    1996-03-01

    Evidence from several laboratories suggests that the ovaries of many species produce a non-steroidal factor called gonadotrophin surge-inhibiting or attenuating factor (GnSIF) which may regulate the response of the pituitary to gonadotrophin-releasing hormone (GnRH) and as such, may modulate the timing and/or amplitude of the luteinizing hormone (LH) surge. We have recently isolated a candidate GnSIF from porcine follicular fluid (PFF). Porcine GnSiF is a 69 kDa protein which has undetectable inhibin and follistatin immunological and biological activity. The present study was designed to purify and identify GnSIF from human follicular fluid. GnSIF activity was measured as suppression of GnRH-stimulated LH secretion from rat pituitary cells in primary culture. Human follicular fluid (approximately 500 ml) was recovered from patients undergoing in-vitro fertilization (IVF). GnSIF was purified by heparin-sepharose, Q-sepharose, S-sepharose, and hydrophobic interaction chromatography followed by isoelectric focusing. Gel electrophoresis and Western blot were used to identify human GnSIF and compare it with porcine GnSIF. Using these steps, we obtained a highly-purified preparation of GnSIF that manifests in-vitro bioactivity and chromatography characteristics similar to those observed for porcine GnSIF and that hybridizes with a porcine GnSIF antibody. Following treatment with human chorionic gonadotrophin/human menopausal gonadotrophin (HMG/HCG), human follicular fluid contained roughly 25% of the GnSIF (per mg protein) present in porcine follicular fluid. We conclude that GnSIF is present in human follicular fluid and may participate in the regulation of gonadotrophin secretion in this species. PMID:8671252

  11. Bilateral follicular cysts in a water buffalo.

    PubMed

    Khan, F A; Nabi, S U; Pande, Megha; Das, G K; Sarkar, M

    2011-03-01

    The present short communication puts on record a case of bilateral, multiple follicular cysts in a water buffalo along with a detailed description of its ovarian biometry and follicular fluid composition. The ovarian weight and biometrical parameters were much higher than in normal cycling buffaloes. A total of three follicular cysts were observed, two on the right ovary and one on the left ovary, measuring 4.9, 3.0 and 2.6 cm yielding 21, 9 and 5 ml of follicular fluid, respectively. The cystic fluid was deep yellow in colour with a viscous consistency. The follicular fluid concentrations of glucose, total protein, cholesterol, acid phosphatase, calcium, phosphorus and progesterone in all the cysts were within the range reported previously in normal buffalo follicular fluid; however, the alkaline phosphatase concentration in cyst 1 and total bilirubin concentration in cysts 1 and 2 were higher than the values in normal follicular fluid. In contrast, the levels of urea nitrogen in cysts 1 and 3, and oestradiol in cyst 3 were lower than the normal values. All the three follicles had an oestradiol to progesterone ratio less than 1. The results of our study suggest that follicular cysts in buffalo are oestrogenically inactive and have an altered concentration of certain biochemical and hormonal constituents. PMID:21086160

  12. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma

    PubMed Central

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E.; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-01-01

    Abstract We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05). We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  13. Association of follicle stimulating hormone receptor promoter with ovarian response in IVF-ET patients

    PubMed Central

    Dan, Wang; Jing, Gao; Liangbin, Xia; Ting, Zhang; Ying, Zeng

    2015-01-01

    Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor (FSHR) gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response. Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response. Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone (FSH) receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses. Results: With a mutation rate of 40%, 63 in 158 cases showed a 29th site G→A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group (60% versus 23.9%; χ2=21.450, p<0.001). Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability (t=0.457, p=0.324) in the basic FSH values between the two groups (normal group, 7.2±2.3 U/L; mutation group, 7.1±2.0 U/L). Conclusion: The activity of FSHR promoter is significantly affected by the 29th site G→A mutation that will weaken promoter activity and result in poor response to FSH. PMID:26730247

  14. Molecular characterization and quantification of the follicle-stimulating hormone receptor in turbot (Scophthalmus maximus).

    PubMed

    Jia, Yudong; Sun, Ai; Meng, Zhen; Liu, Baoliang; Lei, Jilin

    2016-02-01

    Molecular cloning, characterization, and functional analysis of follicle-stimulating hormone receptor (FSHR) in female turbot (Scophthalmus maximus) were evaluated. Results showed that the full-length FSHR cDNA was 3824 bp long and contained a 2202 bp open reading frame that encoded a mature protein of 733 amino acids (aa) and a signal peptide of 18 aa. Multiple sequence analyses showed that turbot FSHR has high homology with the corresponding genes of other teleosts and significant homology with that of Hippoglossus hippoglossus. Turbot FSHR has the typical structural architecture of glycoprotein hormone receptors consisting of a large N-terminal extracellular domain, seven transmembrane domains and short C-terminal intracellular domain. FSHR mRNA was found to be abundant in the ovaries, but deficient in eyes, intestine, brain, muscle, gills, spleen, stomach, heart and kidney. Furthermore, FSHR mRNA was found to increase gradually from pre-vitellogenesis to migratory nucleus stages, with the highest values observed during the late vitellogenesis stage of the reproductive cycle. However, FSHR mRNA was found to decrease dramatically during the atresia stage. Meanwhile, functional analysis with HEK293T cells continual expressing FSHR demonstrated that FSHR was specifically stimulated by ovine FSH, but not ovine LH. These results indicate that turbot FSHR is mainly involved in the stimulation of vitellogenesis, regulation of oocyte maturation as well as promotion of ovarian development via specific ligand binding. These findings open doors to further investigation of physiological functions of FSHR, which will be valuable for fish reproduction and broodstock management. PMID:26358315

  15. Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.

    PubMed

    Kishimoto, Rui; Oki, Kenji; Yoneda, Masayasu; Gomez-Sanchez, Celso E; Ohno, Haruya; Kobuke, Kazuhiro; Itcho, Kiyotaka; Kohno, Nobuoki

    2016-05-01

    We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production.Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production.The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05).We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation. PMID:27196470

  16. Data on the characterization of follicle-stimulating hormone monoclonal antibodies and localization in Japanese eel pituitary.

    PubMed

    Kim, Dae-Jung; Park, Chae-Won; Byambaragchaa, Munkhzaya; Kim, Shin-Kwon; Lee, Bae-Ik; Hwang, Hyung-Kyu; Myeong, Jeong-In; Hong, Sun-Mee; Kang, Myung-Hwa; Min, Kwan-Sik

    2016-09-01

    Monoclonal antibodies were generated against recombinant follicle-stimulating hormone (rec-FSH) from Japanese eel Anguilla japonica; rec-FSH was produced in Escherichia coli and purified using Ni-NTA Sepharose column chromatography. In support of our recent publication, "Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica" [1], it was important to characterize the specificity of eel follicle-stimulating hormone antibodies. Here, the production and ELISA system of these monoclonal antibodies are presented. The affinity-purified monoclonal antibodies specifically detected eel rec-FSH in ELISA and on western blots of rec-FSH produced from CHO cells. Immunohistochemical analysis revealed that FSH staining was specifically localized in the eel pituitary. PMID:27331121

  17. Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

    NASA Technical Reports Server (NTRS)

    Linderman, Jon K.; Whittall, Justen B.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Booth, Frank W.; Grindeland, Richard E.

    1995-01-01

    The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

  18. Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

    PubMed Central

    Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

    2009-01-01

    While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

  19. Two members of a widely expressed subfamily of hormone-stimulated adenylyl cyclases.

    PubMed Central

    Premont, R T; Chen, J; Ma, H W; Ponnapalli, M; Iyengar, R

    1992-01-01

    cDNA encoding a hormone- and guanine nucleotide-stimulated adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] (type 6) from rat liver and kidney has been cloned and expressed. This enzyme is stimulated by forskolin, guanosine 5'-[gamma-thio]triphosphate, and isoproterenol plus GTP but is not stimulated by beta gamma subunits of guanine nucleotide-binding proteins. A second form (type 5), which is 75% similar to type 6, has also been cloned. Both types 5 and 6 cDNAs have multiple messages. PCR-based detection of the mRNA for the type 5 and 6 enzymes indicates that both are widely distributed. Homology analyses indicate at least four distinct subfamilies of guanine nucleotide stimulatory protein-regulated adenylyl cyclases. Types 5 and 6 enzymes define one distinct subfamily of mammalian adenylyl cyclases. Diversity of one guanine nucleotide-binding protein-regulated effector may allow different modes of regulation of cell-surface signal transmission. Images PMID:1409703

  20. Alpha-Melanocyte Stimulating Hormone: An Emerging Anti-Inflammatory Antimicrobial Peptide

    PubMed Central

    Singh, Madhuri; Mukhopadhyay, Kasturi

    2014-01-01

    The alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide belonging to the melanocortin family. It is well known for its anti-inflammatory and antipyretic effects and shares several characteristics with antimicrobial peptides (AMPs). There have been some recent reports about the direct antimicrobial activity of α-MSH against various microbes belonging to both fungal and bacterial pathogens. Similar to α-MSH's anti-inflammatory properties, its C-terminal residues also exhibit antimicrobial activity parallel to that of the entire peptide. This review is focused on the current findings regarding the direct antimicrobial potential and immunomodulatory mechanism of α-MSH and its C-terminal fragments, with particular emphasis on the prospects of α-MSH based peptides as a strong anti-infective agent. PMID:25140322

  1. Alpha-melanocyte-stimulating hormone is a peripheral, integrative regulator of glucose and fat metabolism.

    PubMed

    Brennan, Miles B; Costa, Jessica Lynn; Forbes, Stacy; Reed, Peggy; Bui, Stephanie; Hochgeschwender, Ute

    2003-06-01

    Melanocortins are known to affect feeding and probably insulin activity through the central nervous system. It was also recently shown that peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) administration can reduce weight gain in both genetic and diet-induced obese mice. As obesity is often associated with disregulation of glucose and insulin, we investigated the nature of glucose homeostasis in the obese pro-opiomelanocortin (POMC) knockout mouse. Here we report that though they are obese, mice deficient in POMC (and, thereby, deficient in alpha-MSH) are euglycemic throughout their lives. While these mice are euinsulinemic, they are hypersensitive to exogenous insulin. This defect can be reversed through administration of alpha-MSH. We demonstrate that the actions of alpha-MSH in the periphery, known from our work to include lipid metabolism effects, are also involved in glucose homeostasis. These findings substantiate a pivotal role of the POMC gene products in integrating metabolism. PMID:12851327

  2. Follicle-Stimulating Hormone: A Review of Form and Function in the Treatment of Infertility.

    PubMed

    Smitz, Johan; Wolfenson, Claudio; Chappel, Scott; Ruman, Jane

    2016-06-01

    The use of gonadotropin therapy, including follicle-stimulating hormone (FSH), represents an indispensable part of fertility treatment. There are a number of FSH preparations commercially available or in development, including both urinary-derived products (urinary-derived FSH [uFSH]) and FSH produced through recombinant techniques (recombinant FSH [rFSH]). Differences in the glycosylation patterns of FSH give rise to a number of naturally occurring isoforms that may differ functionally. The relative concentrations of these isoforms vary over the course of the menstrual cycle and the lifetime, indicating that these differences in glycosylation may have physiologic relevance. Although both uFSH and rFSH contain human FSH, there are differences in the glycosylation patterns, which may give rise to differences in biologic activity between products. Current FSH products have been shown to have high purity and to exhibit consistent, favorable efficacy and safety profiles for the treatment of infertility, regardless of urinary or recombinant origin. PMID:26446000

  3. Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone

    SciTech Connect

    Huseman, C.A.; Moriarty, C.M.; Angle, C.R.

    1987-04-01

    Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, they studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 ..mu..g/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T/sub 4/, T/sub 4/, T/sub 3/, cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolcatin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitarities. After incubation of pituitary cells with 0.1-10 ..mu..M Pb/sup 2 +/ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, /sup 45/Ca/sup 2 +/ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 ..mu..M lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity.

  4. The role of melanocyte-stimulating hormone in insulin resistance and type 2 diabetes mellitus.

    PubMed

    Costa, Jessica Lynn; Hochgeschwender, Ute; Brennan, Miles

    2006-01-01

    In humans, mice, and other mammals, the melanocortin system consists of four peptide hormones with a core amino acid sequence of histidine-phenylalanine-arginine-tryptophan and five melanocortin receptors. Both the melanocortin hormones and their receptors are produced in diverse tissues throughout the body. The ligand of primary interest for treatment of insulin resistance is alpha-melanocyte-stimulating hormone (alpha-MSH), which is derived, as are all melanocortins, from tissue-specific post-translational proteolytic processing of the pro-opiomelanocortin (POMC) precursor protein. Recent results have shown that alpha-MSH is the complement of leptin in the endocrine circuit, regulating bodyweight, food intake, and metabolic rate. alpha-MSH can decrease bodyweight, weight gain, and food intake in mice with diet-induced and genetic obesity. As obesity is a major risk factor for type 2 diabetes mellitus, it was reasonable to investigate the endocrine agents involved in obesity for their involvement in diabetes. alpha-MSH analogs have also been shown to affect blood glucose levels in some mouse models of obesity. For instance, the POMC null mouse is extremely sensitive to insulin in an insulin tolerance test, while being otherwise euglycemic. The results from rodent studies with alpha-MSH suggest reciprocal effects: alpha-MSH appears to increase sensitivity to insulin when present in the CNS, while alpha-MSH in the periphery is necessary for insulin resistance. Should these trends be validated in humans, alpha-MSH-based therapeutics specifically active in the CNS or peripheral circulation may be promising for the treatment of type 2 diabetes. PMID:16396514

  5. Properties of follicle-stimulating-hormone receptor in cell membranes of bovine testis.

    PubMed Central

    Cheng, K W

    1975-01-01

    A simple method for preparing plasma membranes from bovine testes is described. Bovine testicular receptor has a high affinity and specificity for 125I-labelled human FSH (follicle-stimulating hormone). The specific binding of 125I-labelled human FSH to the plasma membranes is a saturable process with respect to the amounts of receptor protein and FSH added. The association and dissociation of 125I-labelled human FSH are time- and temperature-dependent, and the binding of labelled human FSH to bovine testicular receptor is strong and not readily reversible. Scatchard [Ann. N.Y. Acad. Sci. (1949) 51, 660-672] analysis indicates a dissociation constant, Kd, of 9.8 X10(-11)M, and 5.9 X 10(-14)mol of binding sites/mg of membrane protein. The testicular membrane receptor is heat-labile. Preheating at 40 degrees C for 15 min destroyed 30% of the binding activity. Specific binding is pH-dependent, with an optimum between pH 7.0 and 7.5. Brief exposure to extremes of pH caused irreversible damage to the receptors. The ionic strength of the incubation medium markedly affects the association of 125I-labelled human FSH with its testicular receptor. Various cations at concentrations of 0.1M inhibit almost completely the binding of 125I-labelled human FSH. Nuclectides and steroid hormones at concentrations of 1mM and 5mu/ml respectively have no effect on the binding of FSH to its receptor. Incubation of membranes with and chymotrypsin resulted in an almost complete loss of binding activity, suggesting that protein moieties are essential for the binding of 125I-labelled human FSH. Binding of 125I-labelled human FSH to bovine testicular receptor does not result in destruction or degradation of the hormone. PMID:242318

  6. Characterization of human follicle-stimulating hormone binding to human granulosa cells by an immunoenzymological method.

    PubMed

    Perrotin, F; Royere, D; Roussie, M; Combarnous, Y; Lansac, J; Müh, J P

    1992-04-01

    An original, nonradiometric method has been developed for studying the binding parameters of native follicle-stimulating hormone (FSH) to its specific receptors in human ovarian granulosa cells. After binding and washing of the cells, hFSH was desorbed from its receptors and quantitatively measured by a specific enzyme immunoassay (EIA) in which nonspecific binding was estimated in the presence of an excess of equine chorionic gonadotropin (eCG/PMSG), which binds to human FSH receptors but does not interfere in the hFSH EIA. This method makes use of native nonmodified hFSH molecules (in contrast to radiometric methods) and permits direct estimation of the binding parameters (Kd and total number of sites). The Kd of hFSH for its human granulosa receptors measured by this technique (4.8 +/- 0.3 x 10(-10) M) is close to that determined by other methods. However, we found a total number of specific FSH receptors per granulosa cell (1 to 6 x 10(4) higher than that reported by others by Scatchard analysis of competition dose-response curves in radioreceptor assays. The method is also sensitive enough to measure the in vivo occupancy of receptors by endogenous hFSH, which was found to be less than 6% in women undergoing hormonal treatment for in vitro fertilization. PMID:1621987

  7. Sensitive and specific immunoradiometric assay (IRMA) for human thyroid stimulating hormone

    SciTech Connect

    Piaditis, G.P.; Hodgkinson, S.C.; McLean, C.; Lowry, P.J.

    1985-01-01

    A liquid phase ''two-site'' immunoradiometric assay (IRMA) specific for human thyroid stimulating hormone (hTSH) is described. The assay is based on the simultaneous addition of affinity purified sheep anti hTSH IgG- SVI and rabbit anti hTSH antiserum to standards and unknowns followed by 4h incubation at room temperature. The separation of free labelled sheep IgG- SVI from that bound to hTSH is achieved by the addition of sheep anti-rabbit IgG Fc fragment antiserum. The radiolabelled sheep anti-hTSH IgG- SVI was pretreated with solid phase urinary postmenopausal gonadotropins to remove cross reaction with FSH and LH. The assay is specific for hTSH and no cross reaction with the other anterior pituitary glycoproteins or protein hormones has been found. In addition it is characterized by a wide operating range, rapid equilibration of reactants and high sensitivity. The precision of dose estimates was less than 10% between 0.25-2.5 microU/ml and less than 2.5% over the range 2.5-60 microU/ml.

  8. Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone.

    PubMed

    McGowan, B M; Minnion, J S; Murphy, K G; Roy, D; Stanley, S A; Dhillo, W S; Gardiner, J V; Ghatei, M A; Bloom, S R

    2014-05-01

    Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the hypothalamic paraventricular nucleus (PVN), an area central to the stress response. The physiological function of relaxin-3 is unknown but previous work suggests a role in appetite control, stimulation of the hypothalamic-pituitary-gonadal axis and stress. Central administration of relaxin-3 induces c-fos expression in the PVN and increases plasma ACTH levels in rats. The aim of this study was to investigate the effect of central administration of human relaxin-3 (H3) on the hypothalamic-pituitary-adrenal (HPA) axis in male rodents in vivo and in vitro. Intracerebroventricular (i.c.v) administration of H3 (5 nmol) significantly increased plasma corticosterone at 30 min following injection compared with vehicle. Intra-PVN administration of H3 (1.8-1620 pmol) significantly increased plasma ACTH at 1620 pmol H3 and corticosterone at 180-1620 pmol H3 at 30 min following injection compared with vehicle. The stress hormone prolactin was also significantly raised at 15 min post-injection compared with vehicle. Treatment of hypothalamic explants with H3 (10-1000 nM) stimulated the release of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), but H3 had no effect on the release of ACTH from in vitro pituitary fragments. These results suggest that relaxin-3 may regulate the HPA axis, via hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central signal linking nutritional status, reproductive function and stress. PMID:24578294

  9. Thyroid Hormone Stimulation of Autophagy Is Essential for Mitochondrial Biogenesis and Activity in Skeletal Muscle.

    PubMed

    Lesmana, Ronny; Sinha, Rohit A; Singh, Brijesh K; Zhou, Jin; Ohba, Kenji; Wu, Yajun; Yau, Winifred W Y; Bay, Boon-Huat; Yen, Paul M

    2016-01-01

    Thyroid hormone (TH) and autophagy share similar functions in regulating skeletal muscle growth, regeneration, and differentiation. Although TH recently has been shown to increase autophagy in liver, the regulation and role of autophagy by this hormone in skeletal muscle is not known. Here, using both in vitro and in vivo models, we demonstrated that TH induces autophagy in a dose- and time-dependent manner in skeletal muscle. TH induction of autophagy involved reactive oxygen species (ROS) stimulation of 5'adenosine monophosphate-activated protein kinase (AMPK)-Mammalian target of rapamycin (mTOR)-Unc-51-like kinase 1 (Ulk1) signaling. TH also increased mRNA and protein expression of key autophagy genes, microtubule-associated protein light chain 3 (LC3), Sequestosome 1 (p62), and Ulk1, as well as genes that modulated autophagy and Forkhead box O (FOXO) 1/3a. TH increased mitochondrial protein synthesis and number as well as basal mitochondrial O2 consumption, ATP turnover, and maximal respiratory capacity. Surprisingly, mitochondrial activity and biogenesis were blunted when autophagy was blocked in muscle cells by Autophagy-related gene (Atg)5 short hairpin RNA (shRNA). Induction of ROS and 5'adenosine monophosphate-activated protein kinase (AMPK) by TH played a significant role in the up-regulation of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), the key regulator of mitochondrial synthesis. In summary, our findings showed that TH-mediated autophagy was essential for stimulation of mitochondrial biogenesis and activity in skeletal muscle. Moreover, autophagy and mitochondrial biogenesis were coupled in skeletal muscle via TH induction of mitochondrial activity and ROS generation. PMID:26562261

  10. Synchronization of ovarian follicular waves with a gonadotropin-releasing hormone agonist to increase the precision of estrus in cattle: a review.

    PubMed

    Twagiramungu, H; Guilbault, L A; Dufour, J J

    1995-10-01

    Treatment with GnRH and PGF2 alpha is a practical method for controlling ovarian follicular and luteal functions and increasing the precision of estrus synchronization in cyclic and acyclic postpartum cows and heifers. This method reduces considerably the period of time needed for estrus detection; it synchronizes the estrous cycle of 70 to 80% of the cyclic cows to within a 4-d interval without any detrimental effect on the fertility rate (65 to 85%). Moreover, resumption of ovarian activity and normal fertility in acyclic cows in favored. Administration of GnRH eliminates the large follicles by ovulation or atresia and induces emergence of a new follicular wave within 3 to 4 d after treatment at any stage of the estrous cycle, but it limits further growth of these emerging follicles by increasing atresia. The precision of estrus and the unaltered fertility rate is due to the synchronized selection of a new larger growing follicle, which becomes the ovulatory follicle after PGF(2 alpha)-induced luteolysis 6 d after GnRH treatment. Also, fixed-time AI programs without the need for estrus detection may be possible using a second injection of GnRH in a GnRH-PGF(2 alpha)-GnRH protocol to ovulate the selected follicle at a precise time. We describe a physiological model to explain how the precision of estrus is improved following PGF(2 alpha)-induced luteolysis, via the effect of pretreatment with GnRH on follicular development and luteal functions in cattle. Application of this model to the development of reliable methods of fixed-time insemination is also explored. PMID:8617687

  11. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    SciTech Connect

    Hsueh, A.J.W.; Dahl, K.D.; Vaughan, J.; Tucker, E.; Rivier, J.; Bardin, C.W.; Vale, W.

    1987-07-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an ..cap alpha beta.. heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the ..cap alpha beta.. heterodimer, the ..beta beta.. homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the ..cap alpha beta.. heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ..beta beta.. homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.

  12. Hormones

    MedlinePlus

    ... the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, thymus, thyroid, adrenal ...

  13. Ovotoxic Effects of Galactose Involve Attenuation of Follicle-Stimulating Hormone Bioactivity and Up-Regulation of Granulosa Cell p53 Expression

    PubMed Central

    Banerjee, Sayani; Chakraborty, Pratip; Saha, Piyali; Bandyopadhyay, Soma Aditya; Banerjee, Sutapa; Kabir, Syed N.

    2012-01-01

    Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol significantly prevented

  14. Normal or induced secretory patterns of luteinising hormone and follicle-stimulating hormone in anoestrous gonadotrophin-releasing hormone-immunised and cyclic control heifers.

    PubMed

    Prendiville, D J; Enright, W J; Crowe, M A; Finnerty, M; Roche, J F

    1996-12-16

    The objective was to determine the effect of gonadotrophin-releasing hormone (GnRH), GnRH analogue (GnRH-A) or oestradiol administration on luteinising hormone (LH) and follicle-stimulating hormone (FSH) release in GnRH-immunised anoestrous and control cyclic heifers. Thirty-two heifers (477 +/- 7.1 kg) were immunised against either human serum albumin (HSA; controls; n = 8), or a HSA-GnRH conjugate. On day 70 after primary immunisation, control heifers (n = 4 per treatment; day 3 of cycle) received either (a) 2.5 micrograms GnRH or (b) 2.5 micrograms of GnRH-A (Buserelin) and GnRH-immunised heifers (blocked by GnRH antibody titre; n = 6 per treatment) received either (c) saline, (d) 2.5 micrograms GnRH, (e) 25 micrograms GnRH or (f) 2.5 micrograms GnRH-A, intravenously. On day 105, 1 mg oestradiol was injected (intramuscularly) into control (n = 6) and GnRH-immunised anoestrous heifers with either low (13.4 +/- 1.9% binding at 1:640; n = 6) or high GnRH antibody titres (33.4 +/- 4.8% binding; n = 6). Data were analysed by ANOVA. Mean plasma LH and FSH concentrations on day 69 were higher (P < 0.05) in control than in GnRH-immunised heifers (3.1 +/- 0.16 vs. 2.5 +/- 0.12 ng LH ml-1 and 22.5 +/- 0.73 vs. 17.1 +/- 0.64 ng FSH ml-1, respectively). The number of LH pulses was higher (P < 0.05) in control than in GnRH-immunised heifers on day 69 (3.4 +/- 0.45 and 1.0 +/- 0.26 pulses per 6 h, respectively). On day 70, 2.5 micrograms GnRH increased (P < 0.05) LH concentrations in control but not in GnRH-immunised heifers, while both 25 micrograms GnRH and 2.5 micrograms GnRH-A increased (P < 0.05) LH concentrations in GnRH-immunised heifers, and 2.5 micrograms GnRH-A increased LH in controls. FSH was increased (P < 0.05) in GnRH-immunised heifers following 25 micrograms GnRH and 2.5 micrograms GnRH-A. Oestradiol challenge increased (P < 0.05) LH concentrations during the 13-24 h period after challenge with a greater (P < 0.05) increase in control than in Gn

  15. Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Ryder, K. D.; Duncan, R. L.

    2000-01-01

    Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

  16. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

    PubMed

    Gowen, M; Stroup, G B; Dodds, R A; James, I E; Votta, B J; Smith, B R; Bhatnagar, P K; Lago, A M; Callahan, J F; DelMar, E G; Miller, M A; Nemeth, E F; Fox, J

    2000-06-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  17. Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats

    PubMed Central

    Gowen, Maxine; Stroup, George B.; Dodds, Robert A.; James, Ian E.; Votta, Bart J.; Smith, Brian R.; Bhatnagar, Pradip K.; Lago, Amparo M.; Callahan, James F.; DelMar, Eric G.; Miller, Michael A.; Nemeth, Edward F.; Fox, John

    2000-01-01

    Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a “calcilytic”) of the parathyroid cell Ca2+ receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17β-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca2+ receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis. PMID:10841518

  18. Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.

    PubMed

    Loutradis, Dimitris; Drakakis, Petros; Vlismas, Antonis; Antsaklis, Aristidis

    2009-04-01

    Corifollitropin alfa is being developed by Schering-Plough Corp as an injectable, long-acting follicle-stimulating hormone (FSH) agonist for the treatment of infertility. A single dose of corifollitropin alfa could initiate and sustain multifollicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection. The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH. Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing. The drug was well tolerated and does not appear to be associated with any serious adverse events or the formation of antibodies. The initial results from a large, phase III, double-blind clinical trial indicated that the ongoing pregnancy rate achieved with corifollitropin alfa treatment was high and similar to the rate established with daily treatment of recombinant FSH. The number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment. Thus, corifollitropin alfa has the potential to serve as a viable fertility agent and to gain a place in the infertility market. PMID:19337959

  19. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S

    PubMed Central

    Bonde, Ylva; Breuer, Olof; Lütjohann, Dieter; Sjöberg, Stefan; Angelin, Bo; Rudling, Mats

    2014-01-01

    Reduced plasma LDL-cholesterol is a hallmark of hyperthyroidism and is caused by transcriptional stimulation of LDL receptors in the liver. Here, we investigated whether thyroid hormone (TH) actions involve other mechanisms that may also account for the reduction in LDL-cholesterol, including effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) and bile acid synthesis. Twenty hyperthyroid patients were studied before and after clinical normalization, and the responses to hyperthyroidism were compared with those in 14 healthy individuals after 14 days of treatment with the liver-selective TH analog eprotirome. Both hyperthyroidism and eprotirome treatment reduced circulating PCSK9, lipoprotein cholesterol, apoB and AI, and lipoprotein(a), while cholesterol synthesis was stable. Hyperthyroidism, but not eprotirome treatment, markedly increased bile acid synthesis and reduced fibroblast growth factor (FGF) 19 and dietary cholesterol absorption. Eprotirome treatment, but not hyperthyroidism, reduced plasma triglycerides. Neither hyperthyroidism nor eprotirome treatment altered insulin, glucose, or FGF21 levels. TH reduces circulating PSCK9, thereby likely contributing to lower plasma LDL-cholesterol in hyperthyroidism. TH also stimulates bile acid synthesis, although this response is not critical for its LDL-lowering effect. PMID:25172631

  20. T follicular regulatory cells.

    PubMed

    Sage, Peter T; Sharpe, Arlene H

    2016-05-01

    Pathogen exposure elicits production of high-affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh-mediated B-cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh-mediated B-cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr-cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody-mediated diseases. PMID:27088919

  1. Effects of inorganic and organic manganese supplementation on gonadotropin-releasing hormone-I and follicle-stimulating hormone expression and reproductive performance of broiler breeder hens.

    PubMed

    Xie, Jingjing; Tian, Chuanhuan; Zhu, Yongwen; Zhang, Liyang; Lu, Lin; Luo, Xugang

    2014-04-01

    Manganese is an essential microelement. Manganese deficiency affects reproduction performance and reproductive hormones in layers. However, little is known about its effects and the possible mechanism in regulating reproduction in broiler breeder hens. In the current study, broiler breeder hens at peak production were fed with diets supplemented with 0, 120, or 240 mg of Mn/kg as MnSO4 or Mn proteinate for 13 wk. Manganese supplementation did not alter egg laying rate, egg weight, fertility, hatchability, or hatchling weight over a 13-wk trial period. However, 240 mg of Mn/kg supplementation significantly increased serum Mn (P < 0.05). Manganese supplements increased the eggshell breaking strength (P < 0.05) without affecting the eggshell thickness. There was no difference in serum cholesterol and estradiol. Expression of follicle-stimulating hormone) and gonadotropin-releasing hormone-I (GnRH-I) genes was significantly elevated by 240 mg of Mn/kg (P < 0.05). Furthermore, inorganic Mn supplementation doubled GnRH-I expression compared with supplementation with the organic form (P < 0.05), although serum Mn was comparable between these 2 supplements. No obvious difference was shown in gene expression of luteinizing hormone, prolactin, GnRH-I receptor, inducible NO synthase, and dopamine receptor D1 in the pituitary as well as tyrosine hydroxylase and inducible NO synthase in the hypothalamus. This suggests that dietary Mn supplementation could improve eggshell quality in the long term. The central mechanism of nontoxic high doses of Mn suggested the transcriptional activation of GnRH-I and follicle-stimulating hormone genes. The central effect of inorganic Mn activating GnRH-I genes compared with the reduced effect by organic Mn could possibly be due to a decreased capacity of the latter passing through the blood-brain barrier. PMID:24706974

  2. Pre-diagnostic circulating follicle stimulating hormone (FSH) concentrations and ovarian cancer risk

    PubMed Central

    McSorley, MA; Alberg, AJ; Allen, DS; Allen, NE; Brinton, LA; Dorgan, JF; Kaaks, R; Rinaldi, S; Helzlsouer, KJ

    2009-01-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between pre-diagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, UK. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to one to two controls on age, menopausal status, time since last menstrual period, current hormone use, and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium, or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend =0.005). Compared to the lowest third of FSH concentrations, the odds ratio among those in the middle and highest thirds were 0.45 (95% Confidence Interval (CI) 0.20– 1.00) and 0.26 (95% CI 0.10–0.70), respectively. Associations persisted after excluding cases diagnosed within five years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  3. The frequency of follicle stimulating hormone receptor gene polymorphisms in Iranian infertile men with azoospermia

    PubMed Central

    Gharesi-Fard, Behrouz; Ghasemi, Zahra; Shakeri, Saeed; Behdin, Shabnam; Aghaei, Fatemeh; Malek-Hosseini, Zahra

    2015-01-01

    Background: Azoospermia is the medical condition of a man not having any measurable level of sperm in his semen. Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that plays an important role in human reproduction because of its essential role in normal spermatogenesis. Various Single Nucleotide Polymorphisms (SNPs) have been reported within FSH receptor (FSHR) gene that may affect the receptor function. Objective: The present study aimed to investigate the correlation between two FSHR SNPs at positions A919G, A2039G, and susceptibility to azoospermia in a group of Iranian azoospermic men. The association between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. Materials and Methods: This case control study was performed on 212 men with azoospermia (126 non-obstructive and 86 obstructive) and 200 healthy Iranian men. Two FSHR gene SNPs were genotyped using PCR-RFLP method. The relationship between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. Results: Statistical analysis indicated that at A919G position, AA genotype and A allele were more frequent in obstructive azoospermia cases compared to non-obstructive or normal men (p=0.001). Regarding A2039G polymorphisms, no significant difference was observed between both azoospermia groups and the controls. The mean level of serum FSH was higher in the non-obstructive men compared to the obstructive patients (23.8 versus 13.8, respectively, p= 0.04). Conclusion: The results of the present study indicated that the genetic polymorphisms in the FSHR gene might increase the susceptibility to azoospermia in Iranian men. PMID:26730241

  4. Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model.

    PubMed

    Botte, D A C; Noronha, I L; Malheiros, D M A C; Peixoto, T V; de Mello, S B V

    2014-08-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option. PMID:24666423

  5. Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model

    PubMed Central

    Botte, D A C; Noronha, I L; Malheiros, D M A C; Peixoto, T V; de Mello, S B V

    2014-01-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP–MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP–MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option. PMID:24666423

  6. Comparison between lactating and non-lactating dairy cows on follicular growth and corpus luteum development, and endocrine patterns of ovarian steroids and luteinizing hormone in the estrous cycles.

    PubMed

    Endo, Natsumi; Nagai, Kiyosuke; Tanaka, Tomomi; Kamomae, Hideo

    2012-10-01

    The dynamics of ovarian follicle, corpus luteum (CL), and peripheral plasma ovarian steroids were compared between lactating and non-lactating cows, and a possible association of pulsatile luteinizing hormone (LH) secretion with the dynamics was examined. Lactating (n=5) and non-lactating (n=5) cows were monitored daily for follicle and CL throughout two consecutive estrous cycles (Day 0: day of ovulation). Blood samples were collected daily and at 15 min intervals for 8h on Days 2, 4, 6, 8, and 14 of the second cycle. Lactating cows had larger CL (25.4 ± 1.8mm vs. 23.5 ± 1.5mm, P<0.01) and greater progesterone concentrations (4.6 ± 1.0ng/ml vs. 3.9 ± 0.9 ng/ml, P<0.01) during mid-luteal phase compared with non-lactating cows. Maximal diameters of the first wave dominant follicle (17.2 ± 1.8mm vs. 15.5 ± 0.8mm) and the ovulatory follicle (17.9 ± 1.2mm vs. 15.2 ± 0.8mm) were greater (P<0.05) in lactating cows than in non-lactating cows during the estrous cycles with two follicular waves, but no significant differences were detected between the groups during the estrous cycles with three follicular waves. Plasma estradiol concentrations did not differ between the groups throughout the experiment. Lactating cows had more LH pulses from Days 2 to 14 than non-lactating cows. These results imply that differences in ovarian dynamics may exist between lactating and non-lactating cows, for which the increased number of LH pulses observed in lactating cows may have responsibility. PMID:22951117

  7. Gender and Age Impact on the Association Between Thyroid-Stimulating Hormone and Serum Lipids.

    PubMed

    Meng, Zhaowei; Liu, Ming; Zhang, Qing; Liu, Li; Song, Kun; Tan, Jian; Jia, Qiang; Zhang, Guizhi; Wang, Renfei; He, Yajing; Ren, Xiaojun; Zhu, Mei; He, Qing; Wang, Shen; Li, Xue; Zheng, Wei; Hu, Tianpeng; Liu, Na; Upadhyaya, Arun; Zhou, Pingping; Zhang, Jianping

    2015-12-01

    The relationship between thyroid-stimulating hormone (TSH) and hyperlipidemia is still a topic of debate. We aimed to explore the impact of gender and age on the association between serum TSH and lipid profile in a large cohort of Chinese.This cross-sectional study enrolled 13,915 participants (8565 male, 5350 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and other serum parameters were collected. The associations between TSH and hyperlipidemia of males and females were analyzed separately after dividing TSH and age into subgroups. Odds ratio for hyperlipidemia was calculated by binary logistic regression models.Young males had significantly higher prevalence of hypercholesterolemia, hypertriglyceridemia, and high serum low-density lipoprotein-cholesterol than females, yet after menopause, females had higher prevalence than males. TSH was positively associated with hyperlipidemia independent of thyroid hormones. Males showed more reduced risks of hyperlipidemia in low TSH concentrations, while females demonstrated more enhanced risks of hyperlipidemia in high TSH concentrations. For instance, if TSH was lower than 0.3 μIU/mL, the risks of developing hypercholesterolemia and hypertriglyceridemia in males were only 0.198 (P < 0.01) and 0.425 (P < 0.05) of the reference TSH risks (between 2.0 and 3.0 μIU/mL), while in females the risks were 0.553 (P < 0.05) and 0.642 (P > 0.05), respectively. If TSH was higher than 4.0 μIU/mL, women displayed significantly higher risks of developing hypertriglyceridemia than the reference TSH risks (P < 0.05), yet, men did not demonstrate such significances.Our results showed thyroid hormone independent positive associations between serum TSH and lipids, which were substantially influenced by gender and age. Males demonstrated more protective effects of low TSH against hyperlipidemia, while females showed

  8. Thyrotropin-releasing hormone accelerates fetal mouse lung ultrastructural maturation via stimulation of extra thyroidal pathway.

    PubMed

    Ansari, M A; Demello, D E; Polk, D H; Devaskar, U P

    1997-11-01

    Maternal administration of TSH-releasing hormone (TRH) in the euthyroid mouse accelerates fetal lung ultrastructural maturation. However, the mechanism(s) of TRH in fetal lung development remains unclear; it could be due to its neuroendocrine and/or neurotransmitter effects. Although the neuroendocrine effect of TRH is mediated via stimulation of the fetal pituitary-thyroid axis, the neurotransmitter effect is mediated via stimulation of fetal autonomic nervous system activity. In the hyt/hyt mouse there is a point mutation in the beta subunit of the TSH receptor in the thyroid gland of the Balb-c mouse. In these mice TSH does not bind to its receptors, leading ultimately to the development of primary hypothyroidism, which is transmitted as an autosomal recessive trait. A maturational delay in the lung ultrastructure of the hyt/hyt mouse fetus has been observed. This investigation was undertaken to study the effect of maternal TRH treatment on lung ultrastructural maturation in the hyt/hyt mouse fetus. If the effect of TRH is mediated via stimulation of fetal pituitary-thyroid axis, TRH treatment should not enhance lung maturity in the hyt/hyt fetus and vice versa. Adult hyt/hyt mice made euthyroid by triiodothyronine supplementation were mated to carry hyt/hyt pups. Saline or TRH (0.4 or 0.6 mg/kg/dose) was administered to the mother (i.p.) on d 16 and 17 (b.i.d.) and on d 18 of pregnancy 1 h before killing (term, approximately 20 d). The fetal lung electron micrographs were subjected to ultrastructural morphometric analysis of the number of lamellar bodies and glycogen/nuclear ratio in type II cells, and the alveolar/parenchymal ratio by Chalkley point counting with an interactive computerized image analyzer (Optimas, Bioscan). Fetal lungs exposed to the lower dose of TRH (n = 7) showed no significant difference in their ultrastructural maturation when compared with saline-treated controls (n = 5). However, fetal lungs exposed to a higher dose of TRH (n = 6

  9. Interleukin 1. alpha. inhibits prostaglandin E sub 2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

    SciTech Connect

    Rettori, V.; McCann, S.M. ); Gimeno, M.F. ); Karara, A. ); Gonzalez, M.C. )

    1991-04-01

    Interleukin 1{alpha} (IL-1{alpha}), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1{alpha} into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1{alpha} caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1{alpha} (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E{sub 2} into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1{alpha} reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1{alpha} suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E{sub 2}-mediated release of LHRH.

  10. Stimulation of cholesterol side-chain cleavage by a luteinizing-hormone-releasing hormone (luliberin) agonist (ICI 118630) in rat Leydig cells.

    PubMed Central

    Sullivan, M H; Cooke, B A

    1983-01-01

    The action of a luliberin (luteinizing-hormone-releasing hormone) agonist (ICI 118630) and lutropin (luteinizing hormone) on the activity of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat Leydig cells has been investigated. This has been carried out by studying the metabolism of exogenous (22R)-22- and 25-hydroxycholesterol to testosterone. It was found that both hydroxycholesterols increased testosterone production to higher levels than achieved by lutropin alone. Addition of luliberin agonist but not lutropin was found to increase further the metabolism of the hydroxycholesterol to testosterone; this occurred in the presence of saturating and subsaturating levels of the hydroxycholesterols. This effect of luliberin agonist was potentiated in the presence of lutropin. The protein synthesis inhibitor, cycloheximide, inhibited the luliberin agonist-induced stimulation of the hydroxycholesterol metabolism. At low calcium levels (1.1 microM), testosterone production was increased by addition of (22R)-22-hydroxycholesterol but the luliberin agonist effect was negated. The calmodulin inhibitor trifluoperazine inhibited (22R)-22-hydroxycholesterol-stimulated steroidogenesis and negated the luliberin agonist effect. These results indicate that luliberin agonist specifically increases the synthesis of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat testis Leydig cells. PMID:6230077

  11. Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells

    PubMed Central

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-01-01

    Summary Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development. PMID:24936466

  12. The application of NIR Raman spectroscopy in the assessment of serum thyroid-stimulating hormone in rats

    NASA Astrophysics Data System (ADS)

    Medina-Gutiérrez, C.; Quintanar, J. Luis; Frausto-Reyes, C.; Sato-Berrú, R.

    2005-01-01

    Serum blood samples of euthyroid and thyroidectomized rats treated with thyrotropin-releasing hormone (TRH) were analyzed on aluminum substrates using the near-infrared Raman spectroscopy (830 nm). Spectra of thyroid-stimulating hormone (TSH), TRH and prolactin standards were obtained. Differences between Raman spectra profiles of control and Tx+TRH samples groups were found. These differences were confirmed by the linear discriminant analysis (LDA), which presents a good classification between groups. It is supposed that these differences are produced by the increment of TSH in the thyroidectomized rats.

  13. Leptin directly acts within the hypothalamus to stimulate gonadotropin-releasing hormone secretion in vivo in rats

    PubMed Central

    Watanobe, Hajime

    2002-01-01

    It is still not known whether leptin, an adipocyte-derived hormone, acts directly within the hypothalamus to stimulate the gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) system. In order to address this question, the present study examined the effects of direct intrahypothalamic perfusions with leptin on the in vivo release of GnRH in ovarian steroid-primed ovariectomized rats utilizing the push-pull perfusion technique. Both α-melanocyte-stimulating hormone (α-MSH) and neuropeptide Y were also measured in the hypothalamic perfusates. In normally fed animals, the leptin infusion was without effect on the release of these three hypothalamic peptides and also without effect on plasma LH and prolactin (PRL), whether leptin was infused into the medial preoptic area (where the majority of GnRH neuronal cell bodies exist) or the median eminence-arcuate nucleus complex (where axon terminals of GnRH neurons are located). In contrast, in 3-day fasted rats leptin was effective in stimulating the secretion of GnRH, α-MSH, and LH, regardless of the site of perfusion. These three hormones were increased in a temporal order of α-MSH, GnRH and LH. Irrespective of the site of perfusion, leptin was without effect on the release of neuropeptide Y. Only when leptin was infused into the median eminence-arcuate nucleus complex was PRL secretion also stimulated, although its onset was 1 h behind that of LH. The leptin-induced elevations of GnRH, α-MSH, LH and PRL were all dose-dependently stimulated by subnormal (1.0 ng ml−1) and normal (3.0 ng ml−1) concentrations of leptin, but at higher concentrations (10 ng ml−1) it did not produce additional effects. Leptin infusion into the anterior hypothalamic area, a control site equidistant from both the medial preoptic area and the median eminence-arcuate nucleus complex, did not produce a significant change in any of the hormones in either the fed or fasted rats. These results demonstrate for the first time that

  14. Immunochemical characterization of two thyroid-stimulating hormone beta-subunit epitopes.

    PubMed Central

    Fairlie, W D; Stanton, P G; Hearn, M T

    1995-01-01

    The epitopes of human thyroid-stimulating hormone (hTSH) recognized by two murine monoclonal antibodies (MAbs), designated MAb 279 and MAb 299, have been characterized. These MAbs are highly specific for the beta-subunit of TSH. The epitope recognized by MAb 279 appears to be completely conserved between bovine and human TSH and partially conserved in the porcine species. The TSH beta-subunit epitope recognized by MAb 299 is only partially conserved between the human, bovine and porcine species. Both MAbs are capable of inhibiting the binding of TSH to its receptor in a TSH radioreceptor assay, indicating that the epitopes either coincide or are located close to the TSH beta-subunit receptor-binding sites. The carbohydrate moieties of the TSH beta-subunit appear to play little or no role in the epitope recognition by MAb 279 or MAb 299 while the integrity of the disulphide bonds are essential. The epitopic recognition may also involve lysine residues, as determined by the immunoreactivity with both MAbs following citraconylation of TSH. In addition, the amino acid sequence region between residues bTSH beta 34-44 could be excised by trypsin digestion of bovine TSH beta (bTSH beta) without eliminating epitopic recognition by either MAb. These results provide further insight into the relationship between the structure of the TSH beta-subunit epitopes and location of the receptor-binding sites. Images Figure 2 PMID:7538754

  15. Monte Carlo loop refinement and virtual screening of the thyroid-stimulating hormone receptor transmembrane domain

    PubMed Central

    Ali, M. Rejwan; Latif, Rauf; Davies, Terry F.; Mezei, Mihaly

    2015-01-01

    Metropolis Monte Carlo (MMC) loop refinement has been performed on the three extracellular loops (ECLs) of rhodopsin and opsin-based homology models of the thyroid-stimulating hormone receptor transmembrane domain, a class A type G protein-coupled receptor. The Monte Carlo sampling technique, employing torsion angles of amino acid side chains and local moves for the six consecutive backbone torsion angles, has previously reproduced the conformation of several loops with known crystal structures with accuracy consistently less than 2 Å. A grid-based potential map, which includes van der Waals, electrostatics, hydrophobic as well as hydrogen-bond potentials for bulk protein environment and the solvation effect, has been used to significantly reduce the computational cost of energy evaluation. A modified sigmoidal distance-dependent dielectric function has been implemented in conjunction with the desolvation and hydrogen-bonding terms. A long high-temperature simulation with 2 kcal/mol repulsion potential resulted in extensive sampling of the conformational space. The slow annealing leading to the low-energy structures predicted secondary structure by the MMC technique. Molecular docking with the reported agonist reproduced the binding site within 1.5 Å. Virtual screening performed on the three lowest structures showed that the ligand-binding mode in the inter-helical region is dependent on the ECL conformations. PMID:25012978

  16. Analysis of the antipyretic action of alpha-melanocyte-stimulating hormone in rabbits.

    PubMed Central

    Clark, W G; Holdeman, M; Lipton, J M

    1985-01-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) or paracetamol was injected into a lateral cerebral ventricle (I.C.V.) of rabbits with elevations in rectal temperature induced by sodium arachidonate (I.C.V.), prostaglandin E2 (I.C.V.) or leucocytic pyrogen (I.V.). alpha-MSH (200 ng) was more effective than paracetamol (0.5 mg) in reducing fever caused by leucocytic pyrogen, but it did not alter hyperthermia induced by sodium arachidonate. In contrast, paracetamol reduced hyperthermic responses to arachidonate by about 70%. Neither alpha-MSH nor paracetamol affected hyperthermic responses to prostaglandin E2. The doses of alpha-MSH and paracetamol used in these experiments did not interfere with thermoregulation in a cold environment (10 degrees C). We conclude (1) that alpha-MSH and paracetamol differ in their central mechanism of antipyresis or (2) that inhibition of arachidonic acid metabolism by paracetamol is not requisite for its antipyretic effect, in which case central release of alpha-MSH may mediate the antipyretic effect of paracetamol. PMID:3858506

  17. Development of Follicle-Stimulating Hormone Receptor Binding Probes to Image Ovarian Xenografts

    PubMed Central

    Lee, Chung-Wein; Guo, Lili; Matei, Daniela; Stantz, Keith

    2015-01-01

    The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells in vitro and tumors xenograft model in vivo. The in vitro binding curve and the average number of FSHR per cell are obtained for OVCAR-3 cells by a high resolution flow cytometer. For the decapeptide, the measured EC50 was 160 μM and the average number of receptors per cell was 1.7 × 107. The decapeptide molecular imaging probe reached a maximum tumor to muscle ratio five hours after intravenous injection and a dose-dependent plateau after 24–48 hours. These results indicate the potential application of a small molecular weight imaging probe specific to ovarian cancer through binding to FSHR. Based on these results, multimeric constructs are being developed to optimize binding to ovarian cells and tumors. PMID:26779384

  18. Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal, and pregnancy factors.

    PubMed

    Trumpff, Caroline; Vandevijvere, Stefanie; Moreno-Reyes, Rodrigo; Vanderpas, Jean; Tafforeau, Jean; Van Oyen, Herman; De Schepper, Jean

    2015-11-01

    The percentage of newborns with a neonatal whole blood thyroid-stimulating hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine deficiency at the population level. However, TSH levels in newborns may be influenced by many factors other than iodine status. The objective of this study was to identify neonatal, maternal, and pregnancy-related determinants of neonatal TSH levels in a retrospective cohort study. The study sample included 313 Belgian mothers and their 4- to 5-year-old children. The children had a neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and blood samples were collected 3 to 5 days after birth. Children with suspected congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (i.e., <37 weeks), or with a low birth weight (i.e., <2500 g) were excluded. Information about maternal and birth-related determinants was collected from the neonatal screening center via a self-administered questionnaire filled in by the mother together with the child's health booklet. Higher TSH levels were found in spring and winter compared to summer and autumn (P = .011). Higher TSH levels were associated with lifetime smoking behavior (up to child birth) in the mother (P = .005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P = .003). This study showed that several neonatal, maternal, and pregnancy-related determinants are influencing neonatal TSH level. PMID:26428622

  19. Alpha-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase.

    PubMed

    Manna, Sunil K; Sarkar, Abira; Sreenivasan, Yashin

    2006-03-01

    Considering the role of interleukin-8 (IL-8) in a large number of acute and chronic inflammatory diseases, the regulation of IL-8-mediated biological responses is important. Alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide, inhibits most forms of inflammation by an unknown mechanism. In the present study, we have found that alpha-MSH interacts predominantly with melanocortin-1 receptors and inhibits several IL-8-induced biological responses in macrophages and neutrophils. It down-regulated receptors for IL-8 but not for TNF, IL-4, IL-13 or TNF-related apoptosis-inducing ligand (TRAIL) in neutrophils. It down-regulated CXCR type 1 and 2 but not mRNA levels. alpha-MSH did not inhibit IL-8 binding in purified cell membrane or affinity-purified CXCR. IL-8 or anti-CXCR Ab protected against alpha-MSH-mediated inhibition of IL-8 binding. The level of neutrophil elastase, a specific serine protease, but not cathepsin G or proteinase 3 increased in alpha-MSH-treated cells, and restoration of CXCR by specific neutrophil elastase or serine protease inhibitors indicates the involvement of elastase in alpha-MSH-induced down-regulation of CXCR. These studies suggest that alpha-MSH inhibits IL-8-mediated biological responses by down-regulating CXCR through induction of serine protease and that alpha-MSH acts as a potent immunomodulator in neutrophil-driven inflammatory distress. PMID:16479540

  20. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture.

    PubMed

    Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

    2013-01-01

    The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL(-1) FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells. PMID:25593684

  1. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture

    PubMed Central

    Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

    2013-01-01

    The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL-1 FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells. PMID:25593684

  2. Monte Carlo loop refinement and virtual screening of the thyroid-stimulating hormone receptor transmembrane domain.

    PubMed

    Ali, M Rejwan; Latif, Rauf; Davies, Terry F; Mezei, Mihaly

    2015-01-01

    Metropolis Monte Carlo (MMC) loop refinement has been performed on the three extracellular loops (ECLs) of rhodopsin and opsin-based homology models of the thyroid-stimulating hormone receptor transmembrane domain, a class A type G protein-coupled receptor. The Monte Carlo sampling technique, employing torsion angles of amino acid side chains and local moves for the six consecutive backbone torsion angles, has previously reproduced the conformation of several loops with known crystal structures with accuracy consistently less than 2 Å. A grid-based potential map, which includes van der Waals, electrostatics, hydrophobic as well as hydrogen-bond potentials for bulk protein environment and the solvation effect, has been used to significantly reduce the computational cost of energy evaluation. A modified sigmoidal distance-dependent dielectric function has been implemented in conjunction with the desolvation and hydrogen-bonding terms. A long high-temperature simulation with 2 kcal/mol repulsion potential resulted in extensive sampling of the conformational space. The slow annealing leading to the low-energy structures predicted secondary structure by the MMC technique. Molecular docking with the reported agonist reproduced the binding site within 1.5 Å. Virtual screening performed on the three lowest structures showed that the ligand-binding mode in the inter-helical region is dependent on the ECL conformations. PMID:25012978

  3. Oral delivery of Bifidobacterium longum expressing α-melanocyte-stimulating hormone to combat ulcerative colitis.

    PubMed

    Wei, Pijin; Yang, Yan; Ding, Qing; Li, Xiuying; Sun, Hanxiao; Liu, Zhaobing; Huang, Junli; Gong, Yahui

    2016-02-01

    α-Melanocyte-stimulating hormone (α-MSH) is a tridecapeptide derived from pro-opiomelanocortin that exhibits potent anti-inflammatory properties by regulating the production of inflammatory mediators. This peptide has been well established in several inflammatory models, including inflammatory bowel disease (IBD). However, its extremely short duration in vivo limits its clinical application. To address this limitation, Bifidobacterium was used here as a carrier to deliver α-MSH. We utilized α-MSH-engineered Bifidobacterium against IBD, which is closely linked to immune and intestinal microbiota dysfunction. First, we constructed a Bifidobacterium longum secreting α-MSH (B. longum-α-MSH). We then tested the recombinant α-MSH expression and determined its bioactivity in HT-29 cells. To assess its effectiveness, B. longum-α-MSH was used against an ulcerative colitis (UC) model in rats induced by dextran sulfate sodium. The data showed that α-MSH expression in B. longum-α-MSH was effective, and its biological activity was similar to the synthesized one. This UC model experiment indicated that B. longum-α-MSH successfully colonized the intestinal gut, expressed bioactive α-MSH and had a significant anti-inflammatory effect. The results demonstrate the feasibility of preventing IBD by using B. longum-α-MSH. PMID:26567174

  4. Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis.

    PubMed

    Wei, Pijin; Yang, Yan; Liu, Zhaobing; Huang, Junli; Gong, Yahui; Sun, Hanxiao

    2016-07-01

    The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy. PMID:26673899

  5. Follicle-stimulating hormone levels in male workers exposed to urban chemical, physical, and psychosocial stressors.

    PubMed

    Tomei, G; Tomao, E; Ciarrocca, M; Rosati, M V; Caciari, T; Gamberale, D; Palermo, P; De Sio, S; Tria, M; Panfili, A; Tomei, F

    2009-07-01

    The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in the follicle-stimulating hormone (FSH) levels in traffic policemen compared to a control group. After excluding the subjects with main confounding factors, traffic policemen and male controls were matched by age, working life, body mass index (BMI), drinking habit, cigarette smoking history, and daily consumption of Italian coffee, 166 traffic policemen and 166 controls were included into the study. FSH levels were significantly higher in traffic policemen compared to male controls (P < 0.05). The distribution of FSH values in traffic policemen and controls was significant (P < 0.05). Our results suggest that occupational exposure to low doses of chemical and psychosocial stressors may alter plasma levels of FSH in traffic policemen more than in the control group. If the results obtained are confirmed by further research, the plasma levels of FSH may be used as early biological markers, valuable for the group, used in occupational set even before the appearance of disorders of male fertility. PMID:19671632

  6. Ovarian Follicular Dynamics, Ovarian Follicular Growth, Oocyte Yield, In vitro Embryo Production and Repeated Oocyte Pick Up in Thai Native Heifers Undergoing Superstimulation

    PubMed Central

    Chasombat, J.; Nagai, T.; Parnpai, R.; Vongpralub, T.

    2013-01-01

    The objective of this study was to compare the effectiveness of the protocols for superstimulation of follicular growth in Thai native heifers. Heifers (n = 20) were randomly divided into four groups of five heifers/group. Heifers were given a single dose by i.m. administration of 100 mg Follicle Stimulating Hormone dissolved in polyvinylpyrrolidone (FSHp) at 24 h. Ovum pick up (OPU) occurred at 72 h (F24O72 protocol; Group 1) or 96 h (F24O96 protocol; Group 2), and at 36 h and OPU at 72 h (F36O72 protocol; Group 3) or 96 h (F36O96 protocol; Group 4) after follicular ablation. The dynamics of ovarian follicular growth were monitored by twice-daily ultrasonographic examinations. Blood sample collections were performed every 12 h after initiation of treatment for assessment of FSH, E2 and P4 profiles. All heifers were subjected to eight repeated sequential sessions of OPU. The follicular deviation commenced 24±5.32 h after follicular ablation in all groups. The circulatory FSH surged quickly from 24 to 36 h (>0.8 ng/ml) after follicular ablation and circulatory estrogen levels steadily increased from 36 h until OPU in all groups. At the end of the OPU sessions, the mean number of aspirated follicles/heifer/session in F36O72 protocol (Group 3) and F36O96 protocol (Group 4) were higher than in the two other groups (p<0.05). The number of cumulus-oocyte complexes (COCs), cleaved and day 8 blastocysts rates in the F36O72 protocol (Group 3) were higher than in the other groups (p<0.05). It can be concluded that a single dose i.m. administration of 100 mg FSHp at 36 h and OPU at 72 h after follicular ablation (F36O72 protocol; Group 3) was the most effective protocol for superstimulation of follicular growth for repeated OPU and subsequent in vitro embryo production in Thai native heifers. PMID:25049814

  7. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist.

    PubMed

    Gong, J G; Campbell, B K; Bramley, T A; Gutierrez, C G; Peters, A R; Webb, R

    1996-07-01

    A novel experimental model was developed in cattle to investigate the requirement for FSH and LH during ovarian follicle growth and development. On Day 5 of the estrous cycle, 7 heifers were each implanted with an osmotic minipump containing a GnRH agonist (GnRHa), Buserelin (release rate, 2.5 micrograms/h). Another 7 heifers served as controls. Each minipump was replaced 28 days later with a second pump, which was left in place for a further 20 days. Blood samples were collected daily throughout the experimental period, and frequent samples were also collected on both days of minipump insertion and at 10 days after insertion of the second pump. The ovaries of all heifers were scanned daily by real-time ultrasonography to monitor follicular dynamics. All controls displayed 2 or 3 waves of FSH and follicular development per estrous cycle during the experiment. Insertion of the first minipump produced a large LH and FSH surge and induced ovulation in all 7 animals. Within 8 days of the start of treatment, serum LH concentrations fell to basal levels; they then remained constant at this level throughout the infusion period, only beginning to recover 4-5 days after the termination of infusion. After the initial increase, FSH returned to basal levels before showing a normal wave that was coincident with the emergence, growth, and regression of a dominant follicle. However, despite the peak levels of FSH, dominant follicles from the next wave failed to grow beyond 7-9 mm; they remained at this size for 3 wk until 3-4 days after insertion of the second minipump, when FSH fell precipitously to reach low levels that were maintained throughout the remainder of the infusion. After this fall in FSH concentrations, these follicles regressed rapidly, and no antral follicles > 4 mm were detected until after the termination of treatment. Thereafter, FSH concentrations increased significantly; the increase was accompanied by the emergence of a follicular wave and development of a

  8. Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction

    PubMed Central

    Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin

    2015-01-01

    Objective To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Methods Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. Results There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Conclusion Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS. PMID:26161335

  9. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis.

    PubMed Central

    Hsueh, A J; Dahl, K D; Vaughan, J; Tucker, E; Rivier, J; Bardin, C W; Vale, W

    1987-01-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an alpha beta heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the alpha beta heterodimer, the beta beta homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrating the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, we have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the alpha beta heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the beta beta homodimer suppresses androgen production. Furthermore, similar modulatory actions of inhibin-related proteins were found in cultured ovarian theca-interstitial cells and theca explants treated with LH. In contrast, treatment with the inhibin-related proteins alone did not affect gonadal steroidogenesis. Our data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops. PMID:3474640

  10. A prospective, randomized, controlled, double-blind, double-dummy comparison of recombinant and urinary HCG for inducing oocyte maturation and follicular luteinization in ovarian stimulation.

    PubMed

    Driscoll, G L; Tyler, J P; Hangan, J T; Fisher, P R; Birdsall, M A; Knight, D C

    2000-06-01

    A randomized, controlled, double-blind, double-dummy, phase III clinical trial was conducted in 84 women to compare the efficacy of a s.c. injection of 250 microg recombinant human chorionic gonadotrophin (rHCG; Ovidrel) to an i.m. injection of 5000 IU urinary HCG (uHCG; Profasi) in inducing folliculogenesis, resumption of oocyte meiosis and luteinization after ovulation induction with recombinant follicle stimulating hormone (Gonal-F). The study primary endpoint was comparison of the number of oocytes retrieved per patient receiving either compound. Secondary comparisons included the number of oocytes retrieved per follicles aspirated; the number of mature oocytes; normally fertilized oocytes; and cleaved embryos. There were no statistically significant differences between groups for the primary endpoint (mean +/- SD oocytes retrieved 10.8 +/- 4.5 for rHCG versus 10.3 +/- 5.1 for uHCG) or each of the secondary endpoints except for increased concentrations of progesterone 6-7 days after rHCG administration (353.2 +/- 215.1 versus 234.1 +/- 129.4 nmol/l; P < 0. 004) and for HCG during the luteal phase following rHCG (P < 0.02). There were also no significant side-effects for either drug. Since the confidence intervals for the difference of the number of oocytes retrieved between the two treatment groups were within the bounds defined by the multi-trial protocol equivalence between rHCG and uHCG could be declared. PMID:10831560

  11. Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

    PubMed Central

    Chitnis, Swati S.; Navlakhe, Rajshri M.; Shinde, Gayatri C.; Barve, Sharmila J.; D'Souza, Serena; Mahale, Smita D.; Nandedkar, Tarala D.

    2008-01-01

    Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic- and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level. (J Histochem Cytochem 56:961–968, 2008) PMID:18645207

  12. MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

    PubMed

    Jiang, H; Ge, X

    2014-01-01

    Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals. PMID:24166991

  13. 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

  14. Lactogenic hormone stimulation and epigenetic control of L-amino acid oxidase expression in lactating mammary glands.

    PubMed

    Fujii, Kazuki; Zhang, Haolin; Usuda, Kento; Watanabe, Gen; Nagaoka, Kentaro

    2015-11-01

    L-amino acid oxidase (LAO), a classic flavoprotein, shows antibacterial activity by producing hydrogen peroxide. LAO exists in many tissues such as salivary gland, thymus, spleen, small intestine and testis. In particular, LAO was highly expressed in mice milk and plays an important factor in innate immunity of mammary glands. However, the mechanism which LAO expression is regulated spatially and temporally in lactating mammary glands has been unclear. In this study, we showed the contribution of lactogenic hormone and epigenetic control on LAO gene expression. In monolayer of mammary epithelial cells, treatment of lactogenic hormone mixture, dexamethasone, insulin and prolactin, did not induce LAO mRNA expression and its promoter activity, even though one of milk protein β-casein expression was stimulated. However, increase of LAO expression was observed when the cells were treated with lactogenic hormones in a 3-dimensional culture. The results of chromatin immunoprecipitation analysis revealed that histone H3K18 acetylation increased and histone H3K27 tri-methylation decreased with lactation, which is associated with a period of high LAO expression. Moreover, the treatment of histone methylation inhibitor (DZNep) as well as histone deacetylation inhibitor (Trichostatine A) induced LAO expression in monolayer of mammary cells. Taken together, this is the first demonstration showing that LAO expression is induced in cell culture, and stimulation of lactogenic hormone and change of histone modification are promising signals to show highly expression of LAO in lactating mammary glands. PMID:25820447

  15. Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses.

    PubMed

    Restifo, Melissa M; Frank, Nicholas; Hermida, Pilar; Sanchez-Londoño, Alfredo

    2016-07-01

    OBJECTIVE To assess effects of withholding feed on thyrotropin-releasing hormone (TRH) stimulation test results used in diagnosis of pituitary pars intermedia dysfunction in horses and determine effects of combined testing on results of the TRH stimulation test and the oral sugar test (OST) used in diagnosis of equine metabolic syndrome. ANIMALS 30 adult horses. PROCEDURES All horses underwent TRH stimulation tests under fed and nonfed conditions, an OST alone, and an OST combined with TRH stimulation testing. For TRH stimulation tests, plasma ACTH concentrations were measured before (baseline) and 10 minutes after (poststimulation) IV TRH administration. For the OST, plasma glucose and insulin concentrations were measured before (baseline) and 60 and 90 minutes after oral corn syrup administration. For combined testing, the TRH stimulation test was initiated immediately after 60-minute posttreatment sample collection for the OST. Results were compared among methods by Wilcoxon matched-pairs, signed rank tests, paired t tests, and Bland-Altman analysis. RESULTS Feeding conditions did not affect median ACTH concentrations when TRH stimulation tests were performed alone. Median baseline ACTH concentration did not differ between TRH stimulation tests performed alone (under fed or nonfed conditions) and those combined with OSTs. Median poststimulation ACTH concentration was significantly lower for combined tests than for solitary TRH stimulation tests. Mean 60-minute plasma glucose concentration was significantly lower for solitary OSTs than for combined tests, but this difference could not be attributed to TRH administration. CONCLUSIONS AND CLINICAL RELEVANCE Combined testing in the manner described impacted ACTH concentrations during TRH stimulation tests and is not recommended at this time. PMID:27347827

  16. Follicular disorders of the face.

    PubMed

    Sardana, Kabir

    2014-01-01

    Follicular disorders are possibly a commonly seen, though rarely reported, group of disorders, which are localized around follicles and appendages and clinically present as small papules. Classically, clinicopathological follicular plugging is seen in the "true" follicular disorders, which are appropriately referred to as follicular keratosis. Another subtype is folliculitis (infectious or noninfectious) and the follicular mimickers that clinically resemble "true" follicular disorders without the follicular keratoses. Acne vulgaris has an amalgamation of all the above lesion types. Our review is aimed at describing all the follicular disorders and gives an algorithm for diagnosing the common follicular disorders. PMID:25441478

  17. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

    NASA Astrophysics Data System (ADS)

    Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

    2014-02-01

    Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

  18. Modulating Intrafollicular Hormonal Milieu in Controlled Ovarian Stimulation: Insights From PPAR Expression in Human Granulosa Cells.

    PubMed

    Tatone, Carla; Benedetti, Elisabetta; Vitti, Maurizio; Di Emidio, Giovanna; Ciriminna, Rosanna; Vento, Maria Elena; Cela, Vito; Borzì, Placido; Carta, Gaspare; Lispi, Monica; Cimini, Anna Maria; Artini, Paolo Giovanni

    2016-04-01

    Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors relevant to steroid metabolism in granulosa cells (GCs). We investigated whether PPARs and their steroidogenic targets were differentially expressed in GCs differentiated under different recombinant or urinary gonadotropin preparations. GCs from women subjected to COS with r-hFSH, r-hFSH/r-hLH, or hMG-HP were processed to assess expression of PPARα, PPARβ/δ, PPARγ, and steroidogenic enzymes under PPAR modulation. As an evidence of their activation, all PPAR isotypes with their coactivators, the retinoic-X-receptors (RXRs), localized in the nucleus. When GCs from r-hFSH/r-hLH group were compared with r-hFSH, a significant reduction of PPARα protein was observed. By contrast, an increase of PPARβ/δ at both protein and mRNA levels along with that of PPARγ protein were detected. The steroidogenic enzymes 17βHSD IV, 3βHSD II, and HMG-CoA red were downregulated in the r-hFSH/r-hLH group in comparison to r-hFSH unlike CYP19A1 that remained unchanged. In GCs from urinary FSH-LH stimulation (hMG-HP), PPARα was more expressed in comparison with r-hFSH/r-hLH group. Likewise, 3βHSD II and 17βHSD IV were increased suggesting that hMG-HP partially mimicked r-hFSH/r-hLH effects. In summary, transcript analysis associated to protein investigation revealed differential effects of COS protocols on PPARs and their steroidogenic targets in relation to LH and gonadotropin source. These observations candidate PPARs as new biomarkers of follicle competence opening new hypotheses on COS effects on ovarian physiology. J. Cell. Physiol. 231: 908-914, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332656

  19. Nocturnal plasma melatonin and alpha-melanocyte stimulating hormone levels during exacerbation of multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1992-01-01

    The pineal gland has been implicated recently in the pathogenesis of multiple sclerosis (MS). To investigate this hypothesis further, we studied nocturnal plasma melatonin levels and the presence or absence of pineal calcification (PC) on CT scan in a cohort of 25 patients (5 men, 20 women; mean age: 41.1 years; SD = 11.1; range: 27-72) who were admitted to a hospital Neurology service for exacerbation of symptoms. Plasma alpha-melanocyte stimulating hormone (alpha-MSH) estimations were included in the study since there is evidence for a feedback inhibition between alpha-MSH and melatonin secretion. Abnormal melatonin levels were found in 13 patients (52.0%), 11 of whom had nocturnal levels which were below the daytime values (i.e., < 25 pg/ml). Although melatonin levels were unrelated to the patient's age and sex, there was a positive correlation with age of onset of symptoms (p < .0001) and an inverse correlation with the duration of illness (p < .05). PC was noted in 24 of 25 patients (96%) underscoring the pathogenetic relationship between MS and the pineal gland. Alpha-MSH levels were undetectable in 15 patients (60.0%), low in two patients (8.0%), normal in seven patients (28.0%), and elevated in one patient (4.0%). Collectively, abnormal alpha-MSH levels were found in over 70% of patients. These findings support the hypothesis that MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha-MSH also occur during exacerbation of symptoms. The relevance of these findings to the pathogenesis of MS are discussed. PMID:1305632

  20. Insulin Receptor Substrate 1, the Hub Linking Follicle-stimulating Hormone to Phosphatidylinositol 3-Kinase Activation.

    PubMed

    Law, Nathan C; Hunzicker-Dunn, Mary E

    2016-02-26

    The ubiquitous phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates many cellular functions. However, the mechanism by which G protein-coupled receptors (GPCRs) signal to activate PI3K is poorly understood. We have used ovarian granulosa cells as a model to investigate this pathway, based on evidence that the GPCR agonist follicle-stimulating hormone (FSH) promotes the protein kinase A (PKA)-dependent phosphorylation of insulin receptor substrate 1 (IRS1) on tyrosine residues that activate PI3K. We report that in the absence of FSH, granulosa cells secrete a subthreshold concentration of insulin-like growth factor-1 (IGF-1) that primes the IGF-1 receptor (IGF-1R) but fails to promote tyrosine phosphorylation of IRS1. FSH via PKA acts to sensitize IRS1 to the tyrosine kinase activity of the IGF-1R by activating protein phosphatase 1 (PP1) to promote dephosphorylation of inhibitory Ser/Thr residues on IRS1, including Ser(789). Knockdown of PP1β blocks the ability of FSH to activate PI3K in the presence of endogenous IGF-1. Activation of PI3K thus requires both PKA-mediated relief of IRS1 inhibition and IGF-1R-dependent tyrosine phosphorylation of IRS1. Treatment with FSH and increasing concentrations of exogenous IGF-1 triggers synergistic IRS1 tyrosine phosphorylation at PI3K-activating residues that persists downstream through protein kinase B (AKT) and FOXO1 (forkhead box protein O1) to drive synergistic expression of genes that underlies follicle maturation. Based on the ability of GPCR agonists to synergize with IGFs to enhance gene expression in other cell types, PP1 activation to relieve IRS1 inhibition may be a more general mechanism by which GPCRs act with the IGF-1R to activate PI3K/AKT. PMID:26702053

  1. Targeted Melanoma Imaging and Therapy with Radiolabeled Alpha-Melanocyte Stimulating Hormone Peptide Analogues

    PubMed Central

    Quinn, Thomas; Zhang, Xiuli; Miao, Yubin

    2010-01-01

    Radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogues have been used to define the expression, affinity and function of the melanocortin-1 receptor (MC1-R). The MC1-R is one of a family of five G-protein linker receptors, which is primarily involved in regulation of skin pigmentation. Over-expression of the MC1-R on melanoma tumor cells has made it an attractive target for the development of α-MSH peptide based imaging and therapeutic agents. Initially, the native α-MSH peptide was radiolabeled directly, but it suffered from low specific activity and poor stability. The addition of non-natural amino acids yielded α-MSH analogues with greater MC-1R affinity and stability. Furthermore, peptide cyclization via disulfide and lactam bond formation as well as site-specific metal coordination resulted in additional gains in receptor affinity and peptide stability in vitro and in vivo. Radiochemical stability of the α-MSH analogues was improved through the conjugation of metal chelators to the peptide’s N-terminus or lysine residues for radionuclide coordination. In vitro cell binding studies demonstrated that the radiolabeled α-MSH analogues had low to subnanomolar affinities for the MC1-R. Biodistribution and imaging studies in the B16 mouse melanoma modeled showed rapid tumor uptake of the radiolabeled peptides, with the cyclic peptides demonstrating prolonged tumor retention. Cyclic α-MSH analogues labeled with beta and alpha emitting radionuclides demonstrated melanoma therapeutic efficacy in the B16 melanoma mouse model. Strong pre-clinical imaging and therapy data highlight the clinical potential use of radiolabeled α-MSH peptides for melanoma imaging and treatment of disseminated disease. PMID:20467398

  2. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    PubMed

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels. PMID:26342297

  3. Gastroparesis - a novel cause of persistent thyroid stimulating hormone elevation in hypothyroidism.

    PubMed

    O S, Khraisha; M M, Al-Madani; A N, Peiris; T K, Paul

    2015-01-01

    Hypothyroidism is easily treated by levothyroxine therapy which has an 80 percent absorption rate, mostly in the jejunum. The replacement dose of daily levothyroxine is usually calculated at 1.6 mcg/kg body weight per day. We report a 77-year-old man who required supraphysiologic thyroxine replacement (>2.7 mcg/ kg/day) to treat his hypothyroidism. The patient was referred for persistent thyroid stimulating hormone (TSH) elevation (40 mcIU/ml) while on 175 mcg of levothyroxine. Patient was compliant with medication. Medical history included diabetes mellitus type 2, cerebrovascular accident, depression, hypertension, hyperlipidemia, atherosclerotic cardiovascular disease, vitamin B12 deficiency, Addison’s disease, as well as a colostomy secondary to diverticulitis. He was taking aspirin, carvedilol, cholecalciferol, finasteride, fluoxetine, furosemide, ketoconazole, levothyroxine, prednisone, and albuterol/ipratropium inhaler. His height was 180.3 cm; weight, 107 kg. Thyroid was impalpable, and he was clinically euthyroid. Despite discontinuation of iron and statin which are known to interfere with thyroxine absorption and crushing of thyroxine tablets to enhance absorption, his TSH remained elevated. Celiac disease and Helicobacter pylori infection were ruled out with serological testing. There was no proteinuria and anti-parietal cell antibody was positive. Gastroparesis was confirmed by gastric emptying study. He continued to require increasing doses of thyroxine with increment to 300 mcg daily. To our knowledge, this is the first documented association between gastroparesis and thyroxine malabsorption. We recommend that gastroparesis be considered in any patient with persistent TSH elevation despite usual thyroxine doses. PMID:25978052

  4. Studies on the structure of the follicle-stimulating hormone receptor using photoaffinity labeling procedures

    SciTech Connect

    Smith, R.A.

    1985-01-01

    The general objective of this project was to study the structure of the follicle stimulating hormone (FSH) receptor using affinity labeling methods. A low density fraction derived from homogenates of bovine testis was found to contain high affinity and low capacity receptors specific for FSH. Electron microscopic examination of the fraction revealed structure resembling multilamellar membranous vesicles (MV). For photoaffinity labeling of the FSH receptors in MV, an azidobenzoyl-/sup 125/I-analog of human FSH was prepared (/sup 125/I-AB-hFSH) and binding of specific FSH receptors was studied. /sup 125/I-AB-hFSH binding of receptors was inhibited in a dose dependent manner by unlabeled hFSH, and binding was not prevented by structurally-related human chorionic gonadotropin (hCG). The formation of photocrosslinked protein of relative molecular mass (M/sub r/) 54,000, 64,000, 76,000, 84,000, 97,000 and 116,000 was found to be inhibited by unlabeled hFSH in a dose related manner, and to be dependent on photoactivation of the FSH derivative. The interpretation of the photoaffinity labeling experiments was that three proteins associated with the FSH receptor were photoaffinity labeled. Analysis by indirect means suggested that the three proteins were assembled to form oligomeric complexes, and based on the intensities and composition of the oligomeric species, spatial relationships of the polypeptides with respect to each other on the membrane surface were deduced. The results of photoaffinity labeling suggest the FSH receptor is composed of three subunits of M/sub r/ 38,000, 48,000, and 81,000 and exists in the membrane in part as a M/sub r/ 330,000 dimer.

  5. alpha-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia.

    PubMed

    Forslin Aronsson, Sa; Spulber, Stefan; Popescu, Laurentiu M; Winblad, Bengt; Post, Claes; Oprica, Mircea; Schultzberg, Marianne

    2006-02-01

    The aim of the study was to investigate the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from proopiomelanocortin (POMC), on the neurodegeneration following global cerebral ischemia and reperfusion in the rat. The biological activities of alpha-MSH include inhibition of inflammatory responses and anti-pyretic effects. Male Sprague-Dawley rats were subjected to four-vessel occlusion (4-VO) global cerebral ischemia followed by reperfusion, and treated with alpha-MSH (intraperitoneally, i.p.) at 30 min, and 24, 48, 72 and 96 h post-ischemia. Stereological quantification of the pyramidal cells in the CA1 area of the hippocampus showed that the number of viable neurons in ischemic rats was 96,945+/-18,610 (means+/-SD) as compared to 183,156+/-49,935 in sham-operated rats (P<0.05). The number of viable neurons after treatment of ischemic rats with alpha-MSH was 162,829+/-34,757, i.e. significantly different from the number of viable neurons in ischemic rats injected with saline (P<0.01). Astrocyte proliferation due to the ischemic insult was markedly reduced by the treatment with alpha-MSH, and the loss in body weight was reduced by alpha-MSH. In conclusion, post-ischemic administration of alpha-MSH was found to provide neuroprotection in the CA1 pyramidal cell layer in the hippocampus, concomitant with a reduction in glial activation, indicating that alpha-MSH or mimetics thereof may have a potential in the treatment of stroke or other neurodegenerative diseases. Further studies will be required to define the post-ischemic time window for administration of alpha-MSH. PMID:16414116

  6. Follicular occlusion tetrad.

    PubMed

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-10-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  7. Follicular occlusion tetrad

    PubMed Central

    Vasanth, Vani; Chandrashekar, Byalakere Shivanna

    2014-01-01

    Follicular occlusion tetrad is a symptom complex consisting of four conditions having a similar pathophysiology. It includes Hidradenitis suppurativa, acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus. The exact pathogenesis of this group of disease is unknown but evidence suggests that they share the same pathological process initiated by follicular occlusion in apocrine gland bearing areas. Though each of these conditions is commonly encountered singly, follicular occlusion tetrad as a symptom complex has been rarely reported in the literature. PMID:25396138

  8. Ovine thyroid stimulating hormone (TSH) heterologously stimulates production of thyroid hormones from Chinese soft-shell turtle (Pelodiscus sinensis) and bullfrog (Rana catesbeiana and Rana rugulosa) thyroids in vitro.

    PubMed

    Huang, Wei-Tung; Chien, Jung-Tsun; Weng, Ching-Feng; Jeng, Yung-Yue; Lu, Li-Chia; Yu, John Yuh-Lin

    2009-06-01

    Thyroid hormones are important for regulating a variety of developmental processes in vertebrates, including growth, differentiation, metamorphosis, and oxidative metabolism. In particular, this study focused on the in vitro production of thyroxine (T(4)) and triiodothyronine (T(3)) from thyroids in American bullfrogs (Rana catesbeiana), Chinese bullfrogs (Rana rugulosa Wiegmann), and Chinese soft-shell turtles (Pelodiscus sinensis) treated with ovine thyroid stimulating hormone (TSH) at different culture intervals (2, 4, 8, and 12 h) and dosages (1, 10, 50 or 100 ng). The levels of T(4) and T(3) in the tested animals were elevated upon stimulation in a time- and dose-dependent manner, indicating de novo synthesis of T(4) and T(3). Significantly higher hormone levels were observed in the Chinese bullfrog compared to the other two species, for both the time-course and dose-response experiments. Although the bullfrog secreted significantly higher levels of T(4) and T(3), a higher T(4)-conversion capacity was found in the Chinese soft-shell turtle. The highest ratios of T(3) to T(4) were observed in the American bullfrog and Chinese soft-shell turtle for the time-course and dose-response experiments, respectively. These findings suggest that the Chinese soft-shell turtle and bullfrog thyroids can accept ovine TSH for T(4)- and T(3)-formation in a time- and dose-dependent manner, supporting the hypothesis that the binding interactions between TSHs and thyroidal receptors are conserved in vertebrates. PMID:19535032

  9. Characterization of lipid droplets in steroidogenic MLTC-1 Leydig cells: Protein profiles and the morphological change induced by hormone stimulation.

    PubMed

    Yamaguchi, Tomohiro; Fujikawa, Noriyuki; Nimura, Satomi; Tokuoka, Yutaro; Tsuda, Sonoka; Aiuchi, Toshihiro; Kato, Rina; Obama, Takashi; Itabe, Hiroyuki

    2015-10-01

    Lipid droplets (LDs) are functional subcellular organelles involved in multiple intracellular processes. LDs are found in nearly all types of eukaryotic cells, but their properties are highly variable in different types of tissues. Steroidogenic cells synthesize steroid hormones de novo from the cholesterol deposited in cytosolic LDs. However, the roles of LD proteins in steroidogenesis under pituitary hormone stimulation have not been well elucidated. The protein profile of isolated LDs from the mouse Leydig tumor cell line MLTC-1 was distinct from that of hepatic cells or macrophages. By proteomic analysis of the components using mass spectrometry, two enzymes for steroidogenesis, 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) and 17 β-hydroxysteroid dehydrogenase type 11 (17βHSD11), were identified in two strong bands in the LD fractions. The LD fraction of MLTC-1 cells also included CYP11A1 and CYP17, suggesting that the LDs contain all the enzymes needed for testosterone synthesis. The steroidogenesis in Leydig cells is activated by luteinizing hormone through a PKA-dependent pathway. Stimulation of MLTC-1 cells with luteinizing hormone or 8-bromo-cAMP caused drastic changes in the morphology of the LDs in the MLTC-1 cells. Upon stimulation, large perinuclear LDs are turned into much smaller LDs and dispersed throughout the cytosol. These results raise the possibility that LDs are involved in a regulatory pathway of steroidogenesis, not just by serving as a storage depot for cholesterol esters, but also by providing enzymes and generating sites for enzymatic activity. PMID:26143378

  10. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    PubMed Central

    Sun, Qi-Hong; Zheng, Yu; Zhang, Xiao-Lin; Mu, Yi-Ming

    2015-01-01

    Background: Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. Methods: A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed. Results: The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females. Conclusions: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females. PMID:26365959

  11. Analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; Barr, R.; O'Connell, G.; Belbeck, L.; McMahon, A.

    1986-02-01

    There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

  12. The Effect of Thyroid-Stimulating Hormone on Tumor Size in Differentiated Thyroid Carcinoma.

    PubMed

    Ozemir, I A; Gurbuz, B; Bayraktar, B; Aslan, S; Başkent, A; Yalman, H; Yigitbasi, R; Alimoglu, O

    2015-12-01

    We evaluated the correlation between serum thyroid-stimulating hormone (TSH) levels and tumor size and other invasiveness parameters of tumor in patients with differentiated thyroid carcinoma (DTC). Several clinical studies have reported that TSH may also have a role as a regulator of the development and function of the thyroid gland. It is currently not clear whether TSH is involved in the existence of thyroid cancer or progression of thyroid cancer or both. Patients with DTC who underwent thyroid surgery between 2003 and 2008 were included this study. Preoperative serum T3, T4, and TSH levels were compared with the size and invasiveness of cancer, retrospectively. DTC was observed in 110 patients over the 5-year period. Seventy-seven (70 %) of them were euthyroid and classified as the "normal-TSH group" (NTG), and 33 (30 %) have an overt or subclinical hyperthyroidism, classified as the "low-TSH group" (LTG). The mean tumor diameter in the LTG was found to be 8.91 ± 8.03 mm; however, it was found to be 18.19 ± 16.24 mm in the NTG. There were significantly differences among the groups related to the diameter of tumor (p = 0.001). Microcarcinoma was determined in 36 patients (46.8 %) in the NTG and 23 patients (69.7 %) in the LTG (p = 0.027). Although there were no significant differences, tumor capsule invasion (33.8 vs. 18.2 %, p = 0.099) and lymphovascular invasion (16.9 vs. 6.1 %, p = 0.130) rates were higher in the NTG. These findings suggest that TSH has effects on growing and proliferation of not only normal thyroid cells but also cancer cells in DTC. This study revealed that serum TSH level can be explored as an important factor that affects the size and invasiveness of tumor in DTC. PMID:27011492

  13. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    SciTech Connect

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  14. Effect of maternal and neonatal factors on cord blood thyroid stimulating hormone

    PubMed Central

    Lakshminarayana, Sheetal G.; Sadanandan, Nidhish P.; Mehaboob, A. K.; Gopaliah, Lakshminarayana R.

    2016-01-01

    Background: Congenital hypothyroidism (CH) is most common preventable cause of mental retardation in children. Cord blood Thyroid Stimulating Hormone (CBTSH) level is an accepted screening tool for CH. Objectives: To study CBTSH profile in neonates born at tertiary care referral center and to analyze the influence of maternal and neonatal factors on their levels. Design: Cross retrospective sectional study. Methods: Study population included 979 neonates (males = 506 to females = 473). The CBTSH levels were estimated using electrochemiluminescence immunoassay on Cobas analyzer. Kit based cut-offs of TSH level were used for analysis. All neonates with abnormal CBSTH levels, were started on levothyroxine supplementation 10 μg/Kg/day and TSH levels were reassessed as per departmental protocol. Results: The mean CBTSH was 7.82 μIU/mL (Range 0.112 to 81.4, SD = 5.48). The mean CBTSH level was significantly higher in first order neonates, neonates delivered by assisted vaginal delivery and normal delivery, delivered at term or preterm, neonates with APGAR score <5 and those needing advanced resuscitation after birth. The CBTSH level >16.10 and <1.0 μIU/mL was found in 4.39 % and 1.02 % neonates respectively. The prevalence rate of CBTSH level >16.1 μIU/mL was significantly higher in neonates delivered by assisted vaginal delivery and normal delivery, term and preterm neonates, APAGR score of <5, presence of fetal distress, need for resuscitation beyond initial steps and in those with birth weight of <1.5 Kg. Three neonates were confirmed to have CH after retesting of TSH level. Conclusions: The CBTSH estimation is an easy, non-invasive method for screening for CH. The cutoff level of CB TSH (μIU/mL) >16.10 and <1.0 led to a recall of 5.41% of neonates which is practicable given the scenario in our Country. The mode of delivery and perinatal stress factors have a significant impact on CBTSH levels and any rise to be seen in the light of these factors. The prevalence

  15. Biopotency in vitro and metabolic clearance rates of five pituitary preparations of follicle stimulating hormone.

    PubMed

    Phillips, D J; Hudson, N L; Lun, S; Condell, L A; McNatty, K P

    1993-01-01

    Five pituitary preparations of follicle stimulating hormone (FSH), namely NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P., were examined for biological activity in terms of their potency in an in vitro bioassay, receptor assay and heterologous radioimmunoassay and in terms of their metabolic clearance rates. In the three assays, Bioscan oFSH was the most potent (P < 0.05) (3- to 5-fold the potency of NIDDK-oFSH-17), with Ovagen being 25-50% the potency of the NIDDK standard (P < 0.05). Folltropin-V and F.S.H.-P. had the lowest potencies in all three assays. For each preparation, the ratio of activities between the assays was not consistent, suggesting that the preparations behaved differently in each assay. In 9 of 10 cases, potency estimates in the heterologous radioimmunoassay were greater than those in the in vitro bioassay or receptor assay. Polyacrylamide gel electrophoresis of the preparations showed banding consistent with the molecular weight of FSH, but also indicated that the preparations were contaminated with other proteins to varying extents. The half-lives of these preparations when injected into the bloodstream of mature female mice were 28.0, 8.6, 13.4, 11.6 and 17.4 min for NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P. respectively. The slopes of the decay rates were significantly different from each other (P < 0.05) except between Ovagen and Folltropin-V. The results of these studies show that a number of widely available FSH preparations have differing biopotencies. Moreover, the biopotency of a preparation in vitro is not related to its metabolic clearance rate, and not all FSH preparations behave identically in different assays. Measures of biopotency in vitro combined with those of metabolic clearance rate may provide useful information on the properties of FSH preparations used for research purposes and for superovulation of farmed livestock. PMID:8265802

  16. Serum follicle-stimulating hormone levels predict time to development of castration-resistant prostate cancer

    PubMed Central

    Hoare, Dylan; Skinner, Thomas A.A.; Black, Angela; Robert Siemens, D.

    2015-01-01

    Introduction: Treatment of advancing prostate cancer focuses on blocking the activation of the androgen receptor with resultant prolonged perturbation of the hypothalamic-pituitary-gonadal axis. Androgen deprivation therapy (ADT) is marked, however, by eventual progression to castration- resistant prostate cancer (CRPC). Emerging evidence has postulated that follicle-stimulating hormone (FSH) may lead to proliferative and mutagenic responses of prostate cancer. We investigated the association of serum FSH and time to castration resistance. Methods: This was a single-centre retrospective study assessing serum FSH levels of patients undergoing ADT for advancing prostate cancer. The primary outcome was time of ADT initiation to the development of CRPC. For each patient on treatment and with castrate levels of testosterone, the maximum FSH value between ADT commencement and CRPC was identified and recorded. FSH was analyzed as a continuous and categorical variable. Cox multivariate regression in a step-wise fashion was used to explore the association between FSH levels and time to CRPC. Results: From a database of 323 prostate cancer patients actively managed with ADT, 103 men had a documented FSH value while castrate, with 45 men progressing to CRPC. The mean ± standard deviation maximum FSH value of these patients was 6.66 ± 4.22 mIU/mL (range: 1.5–28.1). The mean duration from ADT commencement to CRPC was 3.03 ± 0.34 years (range: 0.36–9.71). Univariate analysis suggested a trend of a negative correlation between FSH values and time to castrate resistance. A FSH value of less than or equal to the lowest tertile (4.8 mIU/mL) was associated with a longer time to CRPC (hazard ratio 0.46; p = 0.006). In the Cox regression analysis, elevated FSH was associated with a shorter duration time to CRPC (p = 0.03). Conclusions: This retrospective, single-centre study would suggest there may be an association between serum FSH levels and time to CRPC for men treated

  17. Triacontanol hormone stimulates population, growth and Brilliant Blue R dye removal by common duckweed from culture media.

    PubMed

    Kiliç, Nur Koçberber; Duygu, Ergin; Dönmez, Gönül

    2010-10-15

    This work is focussed on assessing the potentialities of Lemna minor (L.) for the treatment of reactive dyes polluted wastewaters and investigating the possibility of bioremoval performance stimulation by adding triacontanol hormone to the cultures. In the vast literature describing removal of reactive dyes, considering the lack of reports using of common duckweed in wastewater treatment apparently due to the inadequate efficiency. In the present study, the experiments showed that 1 mg l(-1) triacontanol stimulated duckweed growth. The effect of different dye types (Reactive Orange 14, Reactive Red 120, Reactive Black 5, Brilliant Blue R, and Reactive Brilliant Blue R) onto duckweed growth was tested. Plants grew at most in media with Brilliant Blue R. The highest biomass, in terms of frond number (87+/-1.5) were accompanied with 59.6% maximum dye removal were found in samples containing 2.5 mg l(-1) initial Brilliant Blue R and 1 mg l(-1) triacontanol, indicating hormonal stimulation of both activities. The results presented here that L. minor (L.) could be used effectively to treat wastewaters containing dye. PMID:20633998

  18. Multi-scale modelling of ovarian follicular development: From follicular morphogenesis to selection for ovulation.

    PubMed

    Monniaux, Danielle; Michel, Philippe; Postel, Marie; Clément, Frédérique

    2016-06-01

    In this review, we present multi-scale mathematical models of ovarian follicular development that are based on the embedding of physiological mechanisms into the cell scale. During basal follicular development, follicular growth operates through an increase in the oocyte size concomitant with the proliferation of its surrounding granulosa cells. We have developed a spatio-temporal model of follicular morphogenesis explaining how the interactions between the oocyte and granulosa cells need to be properly balanced to shape the follicle. During terminal follicular development, the ovulatory follicle is selected amongst a cohort of simultaneously growing follicles. To address this process of follicle selection, we have developed a model giving a continuous and deterministic description of follicle development, adapted to high numbers of cells and based on the dynamical and hormonally regulated repartition of granulosa cells into different cell states, namely proliferation, differentiation and apoptosis. This model takes into account the hormonal feedback loop involving the growing ovarian follicles and the pituitary gland, and enables the exploration of mechanisms regulating the number of ovulations at each ovarian cycle. Both models are useful for addressing ovarian physio-pathological situations. Moreover, they can be proposed as generic modelling environments to study various developmental processes and cell interaction mechanisms. PMID:26856895

  19. Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor

    PubMed Central

    Fan, Qing R.; Hendrickson, Wayne A.

    2007-01-01

    Follicle stimulating hormone (FSH) is secreted from the pituitary gland to regulate reproduction in vertebrates. FSH signals through a G-protein coupled receptor (FSHR) on the target cell surface. We describe here the strategy to produce a soluble FSH-FSHR complex that involves the co-secretion of a truncated FSHR ectodomain (FSHRHB) and a covalently-linked FSHαβ heterodimer from baculovirus-infected insect cells. FSH binds to FSHRHB with a high affinity comparable to that for the full-length receptor. The crystal structure of the FSH-FSHRHB complex provides explanations for the high affinity and specificity of FSH interaction with FSHR, and it shows an unexpected dimerization of these complexes. Here we also compare the crystal structure with theoretical models of the FSH-FSHR binding mode. We conclude that the FSH-FSHRHB structure gives an authentic representation of FSH binding to intact FSHR. PMID:17045735

  20. Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease

    PubMed Central

    Wolfson, Robert M.; Rachinsky, Irina; Morrison, Deric; Driedger, Al; Spaic, Tamara; Van Uum, Stan H. M.

    2016-01-01

    Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; P = 0.052). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group (P = 0.03). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol. PMID:26977148

  1. Intracerebroventricular infusion of neuropeptide Y up-regulates synthesis and accumulation of luteinizing hormone but not follicle stimulating hormone in the pituitary cells of prepubertal female lambs.

    PubMed

    Wańkowska, Marta; Lerrant, Yannick; Wójcik-Gładysz, Anna; Starzec, Anna; Counis, Raymond; Polkowska, Jolanta

    2002-02-01

    Neuropeptide Y (NPY) is a putative neuroregulator of the reproductive axis in the central nervous system. In this study we evaluated the effects of central infusion of exogenous NPY on the secretory activity of pituitary gonadotrophic cells in prepubertal lambs. Immature female Merino sheep (n=12) were infused of Ringer solution (control) or 50 microg of NPY to the third ventricle for 5 min and then slaughtered 3 h later. Immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) cells were localised by immunohistochemistry using antibody raised against LHbeta and FSHbeta. Messenger RNA analyses were performed by in situ hybridisation using sense and antisense riboprobes produced from beta subunits of LH and FSH cDNA clones. The results were generated by computer image analysis to determine the area fraction occupied by immunoreactive and/or hybridising cells and optical density for immunostaining and hybridisation signal. LH in the blood plasma was determined by radioimmunoassay. It was found, that in the lambs infused with NPY the area fraction and optical density for immunoreactive LH cells and mRNA LHbeta-expressing cells increased significantly (P<0.001), compared to the vehicle-infused animals. The concentration of LH in the blood plasma did not differ between control and treated groups. The NPY infusions had no effect on the immunoreactivity of FSH cells or on expression of mRNA for FSHbeta. In conclusion we suggest that NPY may be an important component of mechanisms stimulating the synthesis and storage but not the release of LH in the pituitary gonadotrophs from prepubertal female sheep. In addition, this effect is specific for LH, no such effect was apparent on FSH. PMID:11841917

  2. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows

    PubMed Central

    SHIMIZU, Takashi

    2016-01-01

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  3. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows.

    PubMed

    Shimizu, Takashi

    2016-08-25

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  4. Central stimulation of hormone release and the proliferative response of lymphocytes in humans.

    PubMed

    Juránková, E; Jezová, D; Vigas, M

    1995-01-01

    The central nervous system (CNS) may communicate with the immune system by direct innervation of lymphoid organs and/or by neurotransmitters and changes in neuroendocrine functioning and hormone release. The consequences of selective transient changes in circulating hormones on immune functioning in humans have not yet been studied. To address this problem, the authors evaluated the lymphoproliferative responses to optimal and suboptimal concentrations of phytohemagglutinin (PHA) and pokeweek mitogen (PWM) under selective enhancement of circulating growth hormone, prolactin, or norepinephrine. The authors failed to demonstrate any effect of elevated growth hormone levels after clonidine challenge on the lymphoproliferative response to mitogens. Similarly, the results did not show any effect of elevated prolactin concentrations induced by domperidone administration on the immune test. Exposure of volunteers to cold resulted in elevation of plasma norepinephrine levels without changes in growth hormone, epinephrine, or cortisol secretion. Cold exposure induced elevation of plasma norepinephrine and reduction of the lymphoproliferative response to the suboptimal dosage of PHA. The reduction was significant 180 and 240 min after exposure. These results are indicative of a relationship between norepinephrine and immunity. PMID:8534322

  5. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. PMID:26589365

  6. Upregulation of TSHR, TTF-1, and PAX8 in Nodular Goiter Is Associated with Iodine Deficiency in the Follicular Lumen

    PubMed Central

    Chen, Lijun; Liang, Bo; Cai, Huiyao; Cai, Qingyan; Shi, Yaxiong

    2016-01-01

    Objective. It has been testified that iodine regulates thyroid function by controlling thyroid-restricted genes expression and is closely related to diffuse goiter and thyroid dysfunction. However, the effects of follicular lumen iodine, the main form of iodine reserve in the body, on thyroid-restricted genes in nodular goiter are poorly understood. In this study, correlations between follicular lumen iodine and the expressions of thyroid stimulating hormone receptor (TSHR), its transcription factors TTF-1, and PAX8 in nodular goiter were investigated. Patients. In this study, 30 resection specimens clinically histopathologically confirmed to have nodular goiter and 30 normal thyroid specimens from adjacent tissues of nodular goiter are used. Measurement. Western blot immunohistochemistry was performed to assay TSHR, TTF-1, and PAX8 in thyrocytes of nodular goiter as well as in extranodular normal thyroid tissues. Meanwhile, follicular lumen iodine of both nodular goiter and extranodular normal thyroid tissues was detected as well. Results. The TSHR, TTF-1, and PAX8 in nodular goiter were significantly higher than those in the controls. The iodine content in nodular goiter was significantly lower than those in control tissues. Conclusion. Upregulation of TSHR, TTF-1, and PAX8 is associated with low follicular lumen iodine content in nodular goiter. PMID:27525008

  7. Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH

    PubMed Central

    Karakaya, Cengiz; Guzeloglu-Kayisli, Ozlem; Hobbs, Rebecca J.; Gerasimova, Tsilya; Uyar, Asli; Erdem, Mehmet; Oktem, Mesut; Erdem, Ahmet; Gumuslu, Seyhan; Ercan, Deniz; Sakkas, Denny; Comizzoli, Pierre; Seli, Emre; Lalioti, Maria D.

    2014-01-01

    Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35–37, 38–40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats—a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function. PMID

  8. Negative energy balance in a male songbird, the Abert's towhee, constrains the testicular endocrine response to luteinizing hormone stimulation

    PubMed Central

    Davies, Scott; Gao, Sisi; Valle, Shelley; Bittner, Stephanie; Hutton, Pierce; Meddle, Simone L.; Deviche, Pierre

    2015-01-01

    ABSTRACT Energy deficiency can suppress reproductive function in vertebrates. As the orchestrator of reproductive function, endocrine activity of the hypothalamo-pituitary–gonadal (HPG) axis is potentially an important mechanism mediating such effects. Previous experiments in wild-caught birds found inconsistent relationships between energy deficiency and seasonal reproductive function, but these experiments focused on baseline HPG axis activity and none have investigated the responsiveness of this axis to endocrine stimulation. Here, we present data from an experiment in Abert's towhees, Melozone aberti, using gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) challenges to investigate whether energy deficiency modulates the plasma testosterone responsiveness of the HPG axis. Wild-caught birds were either ad libitum fed or energetically constrained via chronic food restriction during photoinduced reproductive development. Energy deficiency did not significantly affect the development of reproductive morphology, the baseline endocrine activity of the HPG axis, or the plasma testosterone response to GnRH challenge. Energy deficiency did, however, decrease the plasma testosterone responsiveness to LH challenge. Collectively, these observations suggest that energy deficiency has direct gonadal effects consisting of a decreased responsiveness to LH stimulation. Our study, therefore, reveals a mechanism by which energy deficiency modulates reproductive function in wild birds in the absence of detectable effects on baseline HPG axis activity. PMID:26333925

  9. Increased daylength stimulates plasma growth hormone and gill Na+, K+ and -ATPase Atlantic salmon (Salmo salar )

    USGS Publications Warehouse

    McCormick, S.D.; Bjornsson, Bjorn Thrandur; Sheridan, M.; Eilertson, C.; Carey, J.B.; O'Dea, M.

    1995-01-01

    Atlantic salmon juveniles reared at constant temperature (9–10°C) were exposed to four photoperiod treatment and sampled every 2 weeks from January through May. Fish reared under normal photoperiod exhibited eight-and three fold increases in plasma growth hormone and gill Na+, K+-ATPase activity, respectively, between January and April. Fish exposed to abrupt increases in daylength (LD 15:9) in February or March responded with earlier increases in plasma growth hormone and gill Na+, K+-ATPase activity, and earlier decreases in condition factor relative to fish in the normal photoperiod group. Fish maintained under short daylength (LD 9:15) from January to May exhibited delayed and muted increases in plasma growth hormone and gill Na+, K+-ATPase activity. Plasma thyroxine exhibited a 2.5-fold increase from February to late March in the normal photoperiod group, was generally lower in the LD 9:15 group, but exhibited no obvious response to abrupt increases in daylength. There was an increase in plasma 3,5,3′-triiodo-l-thyronine with time in all groups (43–80%) but no significant response to photoperiod. Plasma levels of somatostatin-25 were highest in the LD 9:15 group, but there was no detectable response to increased daylength in any of the photoperiod treatments. The results indicate that plasma growth hormone is responsive to increased daylength and may be causally related to subsequent increases in gill Na+, K+-ATPase.

  10. Hyperstimulation syndrome: the levels of inhibin A and B in sera and follicular fluids.

    PubMed

    Ulcova-Gallova, Zdenka; Babcova, Katka; Micanova, Zdenka; Bibkova, Katarina; Rumpik, David

    2014-04-01

    Ovarial hyperstimulation syndrome (OHSS) represents a serious problem encountered during in vitro fertilization (IVF). We examined 10 patients with OHSS and 50 women also hormonally stimulated in the process of IVF who had no complications. In all women, we evaluated the number of obtained oocytes and the level of inhibins A and B in sera and follicular fluid collected at the time of ovarial puncture, the day embryo transfer and on the day of positivity for hCG. The level of inhibin B in both fluids was significantly higher (t = 0.0403) in women with high quality of oocytes. The higher level of inhibin A was detected in patients with OHSS at the time of oocyte collection and on the day of embryo transfer. Inhibin B was elevated only at the time of oocyte collection. The levels of inhibin A and B were identical in follicular fluids collected from both ovaries. We observed no statistically significant differences between the levels of inhibin A and B in follicular fluids of women in the absence of OHSS. Evaluation of serum levels of inhibin A and B at the time of oocyte collection may contribute to the prognosis and prevention of OHSS. PMID:24455972

  11. Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway

    PubMed Central

    LIU, TE; WANG, SUWEI; ZHANG, LINA; GUO, LIHE; YU, ZHIHUA; CHEN, CHUAN; ZHENG, JIN

    2016-01-01

    Premature ovarian failure (POF) is a condition affecting 1% of women in the general population, causing amenorrhea, hypergonadotropism and hypoestrogenism before the age of 40. Currently, POF cannot be reversed and, although treatments are available, there is an urgent need for improved treatment strategies. Growth hormone (GH) is a pleiotropic hormone that affects a broad spectrum of physiological functions, from carbohydrate and lipid metabolism to the immune response. GH has previously been used to treat POF in non-transgenic preclinical trials, but the biochemical mechanism underlying these effects are unclear. In the present study, a mouse model of POF was generated using cyclophosphamide. Treatment of POF mice with recombinant mouse growth hormone (rmGH) was revealed to markedly reduce POF histopathology in ovarian tissue, relieve ovarian granulosa cell injury, reduce the number of atretic follicles and significantly increase the number of mature oocytes. Furthermore, an enzyme-linked immunosorbent assay revealed that plasma estradiol levels increased and plasma follicle stimulating hormone levels decreased with time in a group of mice treated with a medium dose of rmGH (0.8 mg/kg) when compared with the POF model group (P<0.05). In addition, reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis demonstrated elevated levels of Notch-1 signaling pathway factors (Notch1, CBF1, and HES1) in wild-type mice and those treated with medium and high doses of rmGH, but not in those treated with low doses of rmGH. In conclusion, GH may promote ovarian tissue repair, estrogen release and oocyte maturation via activation of the Notch-1 signaling pathway in ovarian tissue. PMID:27347041

  12. The porcine ovarian follicle: I. Selected chemical analysis of follicular fluid at different developmental stages.

    PubMed

    Chang, S C; Jones, J D; Ellefson, R D; Ryan, R J

    1976-10-01

    Numerous parameters of the chemical composition of porcine follicular fluid, obtained at different stages of follicle development, were analyzed. The concentrations of electrolytes, glucose, uric acid, selected enzymes, lipids, amino acids, cyclic AMP, and steroid hormones were determined and compared with concentrations in serum. There were both quantitative and qualitative differences in the composition of follicular fluid and plasma. These differences are discussed with regard to follicular development. PMID:183842

  13. The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

    PubMed Central

    Yang, Yanzhou; Chen, Jie; Wu, Hao; Pei, Xiuying; Chang, Qing; Ma, Wenzhi; Ma, Huiming; Hei, Changchun; Zheng, Xiaomin; Cai, Yufang; Zhao, Chengjun; Yu, Jia; Wang, Yanrong

    2015-01-01

    Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID:26539488

  14. Benign follicular tumors*

    PubMed Central

    Tellechea, Oscar; Cardoso, José Carlos; Reis, José Pedro; Ramos, Leonor; Gameiro, Ana Rita; Coutinho, Inês; Baptista, António Poiares

    2015-01-01

    Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients. PMID:26734858

  15. [Acute effects of ventricular and bicameral stimulation on plasma levels of natriuretic hormone].

    PubMed

    Lo Bianco, F; Altamura, G; Bianconi, L; Toscano, S; Pandozi, C; Castro, A; Magliocca, V; Gentilucci, G; Magris, B; Santini, M

    1997-10-01

    Atrial natriuretic factor (ANF) is a peptide produced by the atrium in response to increases in atrial pressure. It is a potent vasodilator and recent studies suggest that ANF may modulate vasomotor changes in patients (pts) with pacemaker (PM) syndrome. To evaluate the incidence of pacing mode on peptide secretion, plasma concentrations of ANF were determined in 32 pts (18 men and 14 women, mean age 71 +/- 4 years) with a DDD PM implant. Blood samples were collected one hour after a randomly assigned PM programming either in VVI or DDD mode at 70 ppm. Mean plasma ANF levels were 84.12 +/- 51 pg/ml in DDD mode and 156.0 +/- 15 pg/ml in VVI mode (p < 0.05). In 12 pts presenting ventriculoatrial retroconduction, the ANF levels were 77.16 +/- 50 pg/ml during DDD stimulation and 219.0 +/- 16 pg/ml during VVI stimulation (p < 0.05). ANF level was 88.50 +/- 46 pg/ml in DDD mode and 114.25 +/- 65 pg/ml in VVI mode in the 20 pts without AV retroconduction (p < 0.05). During DDD mode, 18 patients showed a DVI stimulation whereas 14 showed a VDD stimulation: the mean ANF level was 67.40 +/- 15 pg/ml during DVI and 100.40 +/- 28 pg/ml during VDD stimulation; the difference between these data was not significant. The increase in ANF levels during VVI pacing confirms the lower haemodynamic performance of this stimulation mode. The increase of ANF levels during VVI stimulation, which was in the subgroup without AV retroconduction, confirms the benefits of DDD stimulation also in this group of patients as well. Atrial pacing at physiological rates does not trigger the release of ANF. PMID:9410771

  16. Human follicular fluid and effects on reproduction.

    PubMed

    Basuino, Laís; Silveira, Carolina F

    2016-01-01

    Fertility - the ability to produce offspring - is considered a prerequisite for the development and perpetuation of species. Several factors may positively or negatively affect one's reproductive capabilities, such as regular exercises and maintaining a healthy bodyweight, versus aging, obesity, and stress. Follicular fluid (FF) is a liquid composed primarily of hormones, enzymes, anticoagulants, electrolytes, reactive oxygen species and antioxidants, which fills the follicular antrum and acts as an important mediator in the communication between cells in the antral follicle while bathing and carrying nutrients to the oocyte. Thus, human FF is a key element to the success of natural fertilization present in every stage of the conception process, from the communication between gametes to the development of fully viable embryos, and a vital component in the occurrence of spontaneous pregnancies. This literature review aimed to describe the possible effects of human follicular fluid on the natural fertilization process and to assess its role in follicular growth, oocyte quality, sperm capacitation, fertilization, and early embryonic development. PMID:27203305

  17. Polymorphism of follicle stimulating hormone beta (FSHβ) subunit gene and its association with litter traits in giant panda.

    PubMed

    Huang, Xiaoyu; Li, Desheng; Wang, Jiwen; Huang, Yan; Han, Chunchun; Zhang, Guiquan; Huang, Zhi; Wu, Honglin; Wei, Ming; Wang, Guosong; Hu, Haiping; Deng, Tao; He, Tao; Zhou, Yingming; Song, Shixian; Luo, Bo; Zhang, Heming

    2013-11-01

    The different SSCP patterns of the follicle stimulating hormone beta (FSHβ) gene amplified by three pairs of primers were sequenced. Comparisons among the three nucleotide sequences of three genotypes indicated that three base substitutions (A213T, A91G, and A89C) were detected in FSHβ gene, which A213T substitution led to one amino acids mutation (Lys > Met), and the other two substitutions were synonymous mutations. The AA, AB and BB genotypes patterns obtained by FSHβ primer1 had evident relation with the litter traits, but the SSCP genotypes patterns obtained by FSHβ primer2 and primer3 had no evident relation with the litter traits in giant panda. The giant panda with AA and AB genotype had the largest litter size and multiparity rate compared with the BB genotypes (P < 0.05). We speculated that the giant pandas with the A allele have better litter traits than those with the B allele. PMID:24057246

  18. Ascorbic acid treatment elevates follicle stimulating hormone and testosterone plasma levels and enhances sperm quality in albino Wistar rats

    PubMed Central

    Okon, Uduak Akpan; Utuk, Ikponoabasi Ibanga

    2016-01-01

    Background: Infertility issues have been linked to the effect of oxidative reaction in the reproductive system. This study evaluated the effect of ascorbic acid, on fertility parameters of male albino Wistar rats was studied. Materials and Methods: Eighteen albino Wistar rats weighed between 178 g and 241 g were used, randomly assigned into three groups. Group 1 was the control group; oral gavaged 5 ml of distilled water; Groups 2 and 3 were administered medium dose (250 mg/kg) and high dose of ascorbic acid (400 mg/kg), respectively; twice daily for 21 days. Blood samples were obtained by cardiac puncture, and blood serum was obtained for hormonal assay, and the testes were harvested for sperm analysis. Results: Follicle stimulating hormone levels significantly increased in the high-dose group as compared to both the control and medium dose groups. Luteinizing hormone levels in the medium dose group decreased significantly as compared to the control group. Testosterone significantly increased in both the medium- and high-dose groups as compared to the control group. Sperm motility increased significantly in the high-dose group as compared to both control and medium-dose groups. Percentage sperm concentration decreased significantly in the medium-dose group when compared to the control and increased significantly in the high-dose group as compared to the medium-dose group. For percentage normal morphology, there was a dose-dependent increase in the test groups when compared to control group. Conclusion: These results are indicative of a positive influence of ascorbic acid on male fertility modulators and may therefore, serve as a potential adjuvant treatment for male infertility cases. PMID:27185976

  19. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats.

    PubMed

    Liu, Changjiang; Zhao, Letian; Wei, Li; Li, Lianbing

    2015-08-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones. PMID:25913319

  20. Identification of calcitonin expression in the chicken ovary: influence of follicular maturation and ovarian steroids.

    PubMed

    Krzysik-Walker, Susan M; Ocón-Grove, Olga M; Maddineni, Sreenivasa B; Hendricks, Gilbert L; Ramachandran, Ramesh

    2007-10-01

    Calcitonin (CALCA), a hormone primarily known for its role in calcium homeostasis, has recently been linked to reproduction, specifically as a marker for embryo implantation in the uterus. Although CALCA expression has been documented in several tissues, there has been no report of production of CALCA in the ovary of any vertebrate species. We hypothesized that the Calca gene is expressed in the chicken ovary, and its expression will be altered by follicular maturation or gonadal steroid administration. Using RT-PCR, we detected Calca mRNA and the calcitonin receptor (Calcr) mRNA in the granulosa and theca layers of preovulatory and prehierarchial follicles. Both CALCA and Calca mRNA were localized in granulosa and thecal cells by confocal microscopy. Using quantitative PCR analysis, F1 follicle granulosa layer was found to contain significantly greater Calca mRNA and Calcr mRNA levels compared with those of any other preovulatory or prehierarchial follicle. The granulosa layer contained relatively greater Calca and Calcr mRNA levels compared with the thecal layer in both prehierarchial and preovulatory follicles. Progesterone (P(4)) treatment of sexually immature chickens resulted in a significantly greater abundance of ovarian Calca mRNA, whereas estradiol (E(2)) or P(4) + E(2) treatment significantly reduced ovarian Calca mRNA quantity. Treatment of prehierarchial follicular granulosa cells in vitro with CALCA significantly decreased FSH-stimulated cellular viability. Collectively, our results indicate that follicular maturation and gonadal steroids influence Calca and Calcr gene expression in the chicken ovary. We conclude that ovarian CALCA is possibly involved in regulating follicular maturation in the chicken ovary. PMID:17582014

  1. Thyroid-Stimulating Hormone Increases HNF-4α Phosphorylation via cAMP/PKA Pathway in the Liver

    PubMed Central

    Song, Yongfeng; Zheng, Dongmei; Zhao, Meng; Qin, Yejun; Wang, Tingting; Xing, Wanjia; Gao, Ling; Zhao, Jiajun

    2015-01-01

    Hepatocyte nuclear factor-4 alpha (HNF-4α) is an orphan nuclear receptor with important roles in hepatic metabolism. Protein phosphorylation plays a functional role in its nuclear localization, DNA binding, and transactivation. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland, whose direct effect on the metabolic pathway has been observed. Our previous study demonstrated that TSH significantly decreases hepatic nuclear HNF-4α expression. However, whether TSH can influence HNF-4α phosphorylation is unclear. Here, we discovered that TSH can increase HNF-4α phosphorylation and modulate its subcellularlocalization. When HepG2 cells were treated with TSH, the phosphorylation of HNF-4α increased and its nuclear localization was interrupted. Cytoplasmic HNF-4α increased, while nuclear HNF-4α decreased. When the cAMP/PKA pathway was inhibited by the PKA inhibitor H89 and the adenylate cyclase (AC) inhibitor SQ22536, the TSH-mediated phosphorylation of HNF-4α was disrupted. When Tshr was silenced in mice, the phosphorylation of HNF-4α decreased, and cytoplasmic HNF-4α decreased while nuclear HNF-4α increased. In conclusion, our study revealed a novel mechanism by which TSH regulated the hepatic HNF-4α subcellular localization, suggesting the possibility that one of the effects of TSH is to reduce the expression of HNF-4α target genes. PMID:26302721

  2. Helodermin-like peptides in thyroid C cells: stimulation of thyroid hormone secretion and suppression of calcium incorporation into bone.

    PubMed Central

    Grunditz, T; Persson, P; Håkanson, R; Absood, A; Böttcher, G; Rerup, C; Sundler, F

    1989-01-01

    Helodermin is a vasoactive intestinal peptide-like peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides coexist with calcitonin. The results of radioimmunoassay agreed with the immunocytochemical findings. HPLC of rat thyroid extracts revealed one major peak of helodermin-like immunoreactivity, which eluted in a position close to that of lizard helodermin. Helodermin stimulated basal thyroid hormone secretion and colloid droplet formation in conscious mice. The effect of large doses of helodermin was quite long-lasting and the maximal response occurred after 2-6 hr. In addition, helodermin suppressed the incorporation of calcium into bone in conscious rats. The findings suggest that helodermin-like peptides in C cells may be involved in the local regulation of thyroid hormone secretion and in the maintenance of calcium homeostasis. Images PMID:2645580

  3. Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

    PubMed Central

    2012-01-01

    Background The placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas. Methods We aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR. Results CRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h. Conclusion The relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction. PMID

  4. Thyroid-Stimulating Hormone Suppression for Protection Against Hypothyroidism Due to Craniospinal Irradiation for Childhood Medulloblastoma/Primitive Neuroectodermal Tumor

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Collini, Paola; Seregni, Ettore; Marchiano, Alfonso; Serra, Annalisa; Pignoli, Emanuele Ph.D.; Spreafico, Filippo; Pallotti, Federica; Terenziani, Monica; Biassoni, Veronica; Bombardieri, Emilio; Fossati-Bellani, Franca

    2007-10-01

    Purpose: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. Patients and Methods: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered L-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 {mu}M/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Results: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the 'adequately TSH-suppressed' group and 20% for the 'inadequately TSH-suppressed' group (p = 0.02). Conclusions: Thyroid-stimulating hormone suppression with L-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.

  5. Diagnosis and discrimination of autoimmune Graves' disease and Hashimoto's disease using thyroid-stimulating hormone receptor-containing recombinant proteoliposomes.

    PubMed

    Fukushima, Hidetaka; Matsuo, Hideaki; Imamura, Koji; Morino, Kazuhiko; Okumura, Katsuzumi; Tsumoto, Kanta; Yoshimura, Tetsuro

    2009-12-01

    Graves' disease (GD) is an autoimmune disease of the thyroid gland caused by autoantibodies against thyroid-stimulating hormone receptor (TSHR). Currently, the diagnostic test for TSHR autoantibodies is based on an indirect competitive binding assay that measures the ability of TSHR autoantibodies to inhibit the binding of thyroid-stimulating hormone (TSH) to TSHR. Here, we have developed a specific and direct diagnostic method for autoantibodies in GD that incorporates immobilized TSHR-containing recombinant proteoliposomes into an enzyme-linked immunosorbent assay (ELISA). To reduce non-specific binding of autoantibodies to recombinant proteoliposomes, we investigated the effect of polyethylene glycol (PEG)-lipid on the binding of commercially available anti-TSHR antibodies (aTSHRAb). The incorporation of PEG-lipids into liposomes decreased non-specific binding, as compared to liposomes that did not contain PEG-lipids, and the addition of blocking reagents further decreased non-specific reactivity. aTSHRAb exhibited higher reactivity towards PEG-modified TSHR recombinant proteoliposomes than PEG-modified liposomes without TSHR (bare liposomes). Importantly, serum autoantibodies from patients with GD, which is associated with hyperthyroidism, exhibited remarkably specific binding to TSHR recombinant proteoliposomes. Serum autoantibodies from patients with Hashimoto's disease (HD), which is associated with hypothyroidism, also reacted specifically with proteoliposomal TSHR. These results suggest that immobilized TSHR recombinant proteoliposomes can serve as a direct diagnostic test for GD and HD. Furthermore, given that there is no competition test currently available for detecting autoantibodies in HD, the combination of TSHR recombinant proteoliposome ELISA and indirect competitive TSHR binding assay might be an effective way to discriminate between GD and HD. PMID:19914592

  6. Follicle Stimulating Hormone and Anti-Müllerian Hormone per Oocyte in Predicting in vitro Fertilization Pregnancy in High Responders: A Cohort Study

    PubMed Central

    Weghofer, Andrea; Kim, Ann; Barad, David H.; Gleicher, Norbert

    2012-01-01

    Background Follicle stimulating hormone (FSH) and Anti-Müllerian hormone (AMH) are utilized to differentiate between good and poor response to controlled ovarian hyperstimulation. Their respective roles in defining functional ovarian reserve remain, however, to be elucidated. To better understand those we investigated AMH and FSH per oocyte retrieved (AMHo and FSHo). Methodology/Principal Findings Three-hundred and ninety-six women, undergoing first in vitro fertilization cycles, were retrospectively evaluated. Women with oocyte yields >75th percentile for their age group were identified as high responders. In a series of logistic regression analyses, AMHo and FSHo levels were then evaluated as predictive factors for pregnancy potential in high responders. Patients presented with a mean age of 38.0±5.0 years, mean baseline FSH of 11.8±8.7 mIU/mL and mean AMH of 1.6±2.1 ng/mL. Those 88 women, who qualified as high responders, showed mean FSH of 9.7±6.5 mIU/mL, AMH of 3.1±3.1 ng/mL and oocyte yields of 15.8±7.1. Baseline FSH and AMH did not predict pregnancy in high responders. However, a statistically significant association between FSHo and pregnancy was observed in high responders, both after univariate regression (p = 0.02) and when adjusted for age, percentage of usable embryos, and number of embryos transferred (p = 0.03). Rate of useable embryos also significantly affected pregnancy outcome independently of FSHo (p = 0.01). AMHo was also associated with clinical pregnancy chances in high responders (p = 0.03) and remained significant when adjusted for usable embryos and number of embryos transferred (p = 0.04). Conclusions AMHo and FSHo are predictive of pregnancy potential in high responders, but likely reflect different responsibilities in recruitment and maturation of growing follicle cohorts. PMID:22545082

  7. The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

    PubMed Central

    Barbakadze, Ludmila; Kristesashvili, Jenara; Khonelidze, Natalia; Tsagareishvili, Gia

    2015-01-01

    Background The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and antral follicle count (AFC) and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39), group II 35-40 years (n=31), and group III 41-46 years (n=42). AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results There was a significantly elevated negative correlation between age and AMH level (rs=-0.67, p<0.0001) and AFC (rs=-0.55, p<0.0001). We observed a significantly positive correlation between age and FSH (rs=0.38, p<0.0001). AMH negatively correlated with FSH (rs=-0.48, p<0.0001) and positively with AFC (r=-0.71, p=0.0001). There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001) and moderate positive relation between age and FSH (rs=0.38, p<0.0001). The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001), group II (r=0.69, p<0.0001) and group III (r=0.47, p<0.002). A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02) and II (r=-0.55, p<0.0001). A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006), as well as between age and AFC only in group I (r=-0.35, p<0.03). Conclusion Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation. PMID:25780521

  8. [Stimulation of somatotropin hormone by piribedil, a dopaminergic agonist, in endogenous depression. Preliminary study].

    PubMed

    Guillaume, R; Charles, G; Mesters, P; Schittecatte, M; Wilmotte, J

    1988-01-01

    Piribedil, a dopaminergic agonist, was administered intravenously (0.5 mg over 10 minutes) to two unipolar endogenous depressed. The two patients, a 38-year-old man and a 60-year-old woman, were matched for age and sex with two volunteers without any mental illness. Effects of piribedil on plasma levels of growth hormone and on blood pressure were studied. The two volunteers evaluated their "feelings" of anxiety and of physical comfort using visual analogue scales. The experimentation was repeated in a double blind fashion with a placebo. Piribedil induced an elevation of GH in the normal man but not in the depressed man. In contrast, no increase was noted in women. No elevation of GH was observed after placebo. Importance of factors such as depression, sexual steroid environment and influence of stress are discussed. PMID:2905110

  9. Purification of bovine thyroid-stimulating hormone by a monoclonal antibody

    SciTech Connect

    Lock, A.J.; van Denderen, J.; Aarden, L.A.

    1988-01-01

    A monoclonal antibody directed against bovine TSH was obtained by hybridoma technology. This antibody was specific for TSH and did not react with bovine LH and FSH. Affinity chromatography of crude TSH was performed on anti-TSH Sepharose. Bovine TSH was purified in a single step to near homogeneity by this technique, as shown by cation exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified TSH. The biological activity of the hormone was not affected during the purification, as determined by (/sup 3/H)thymidine incorporation of the TSH-dependent FRTL5 cell line. The results indicate that affinity purification of TSH by means of a monoclonal antibody is a simple one-step procedure for the production of biologically active, highly purified TSH.

  10. Dehydroepiandrosterone Sulfate (DHEAS) Stimulates the First Step in the Biosynthesis of Steroid Hormones

    PubMed Central

    Neunzig, Jens; Bernhardt, Rita

    2014-01-01

    Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid in human, with the highest concentrations between age 20 and 30, but displaying a significant decrease with age. Many beneficial functions are ascribed to DHEAS. Nevertheless, long-term studies are very scarce concerning the intake of DHEAS over several years, and molecular investigations on DHEAS action are missing so far. In this study, the role of DHEAS on the first and rate-limiting step of steroid hormone biosynthesis was analyzed in a reconstituted in vitro system, consisting of purified CYP11A1, adrenodoxin and adrenodoxin reductase. DHEAS enhances the conversion of cholesterol by 26%. Detailed analyses of the mechanism of DHEAS action revealed increased binding affinity of cholesterol to CYP11A1 and enforced interaction with the electron transfer partner, adrenodoxin. Difference spectroscopy showed Kd-values of 40±2.7 µM and 24.8±0.5 µM for CYP11A1 and cholesterol without and with addition of DHEAS, respectively. To determine the Kd-value for CYP11A1 and adrenodoxin, surface plasmon resonance measurements were performed, demonstrating a Kd-value of 3.0±0.35 nM (with cholesterol) and of 2.4±0.05 nM when cholesterol and DHEAS were added. Kinetic experiments showed a lower Km and a higher kcat value for CYP11A1 in the presence of DHEAS leading to an increase of the catalytic efficiency by 75%. These findings indicate that DHEAS affects steroid hormone biosynthesis on a molecular level resulting in an increased formation of pregnenolone. PMID:24586990

  11. Follicular cell-derived thyroid cancer.

    PubMed

    Dralle, Henning; Machens, Andreas; Basa, Johanna; Fatourechi, Vahab; Franceschi, Silvia; Hay, Ian D; Nikiforov, Yuri E; Pacini, Furio; Pasieka, Janice L; Sherman, Steven I

    2015-01-01

    Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies. PMID:27188261

  12. Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver

    PubMed Central

    Zhang, Xiujuan; Song, Yongfeng; Feng, Mei; Zhou, Xinli; Lu, Yingli; Gao, Ling; Yu, Chunxiao; Jiang, Xiuyun; Zhao, Jiajun

    2015-01-01

    Cholesterol homeostasis is strictly regulated through the modulation of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis. Phosphorylation of HMGCR inactivates it and dephosphorylation activates it. AMP-activated protein kinase (AMPK) is the major kinase phosphorylating the enzyme. Our previous study found that thyroid-stimulating hormone (TSH) increased the hepatocytic HMGCR expression, but it was still unclear whether TSH affected hepatic HMGCR phosphorylation associated with AMPK. We used bovine TSH (bTSH) to treat the primary mouse hepatocytes and HepG2 cells with or without constitutively active (CA)-AMPK plasmid or protein kinase A inhibitor (H89), and set up the TSH receptor (Tshr)-KO mouse models. The p-HMGCR, p-AMPK, and related molecular expression were tested. The ratios of p-HMGCR/HMGCR and p-AMPK/AMPK decreased in the hepatocytes in a dose-dependent manner following bTSH stimulation. The changes above were inversed when the cells were treated with CA-AMPK plasmid or H89. In Tshr-KO mice, the ratios of liver p-HMGCR/HMGCR and p-AMPK/AMPK were increased relative to the littermate wild-type mice. Consistently, the phosphorylation of acetyl-CoA carboxylase, a downstream target molecule of AMPK, increased. All results suggested that TSH could regulate the phosphorylation of HMGCR via AMPK, which established a potential mechanism for hypercholesterolemia involved in a direct action of the TSH in the liver. PMID:25713102

  13. Quantification of follicle stimulating hormone (follitropin alfa): is in vivo bioassay still relevant in the recombinant age?

    PubMed

    Driebergen, R; Baer, G

    2003-01-01

    Quantification of follicle-stimulating hormone (FSH) for clinical use has traditionally involved the use of in vivo bioassays, particularly the Steelman-Pohley bioassay. This assay has limited precision, requires large numbers of laboratory animals and involves cumbersome procedures for data generation and interpretation. Recent advances in manufacturing procedures for recombinant human FSH (r-hFSH) have resulted in a preparation (follitropin alfa; Gonal-F) that is highly consistent in both isoform profile and glycan species distribution. As a result, follitropin alfa can be reliably quantified using an optimised size exclusion high-performance liquid chromatography (SE-HPLC) method, and vials can be filled by mass. Preliminary clinical studies suggest that the fill-by-mass process results in a product that delivers a more consistent clinical response and is more effective than follitropin alfa vials filled by bioassay in women undergoing controlled ovarian stimulation. Non-bioassay methods such as SE-HPLC are likely to become increasingly important for quality testing and regulatory purposes, provided that the manufacturing process is well controlled and produces a protein of highly consistent physico-chemical properties. PMID:12661779

  14. Association of inhibin-α gene polymorphisms with follicular cysts in large white sows.

    PubMed

    Li, Wanhong; Sun, Lina; Chen, Shuxiong; Chen, Lu; Liu, Zhuo; Hou, Xiaofeng; Chen, Chao; Han, Yamei; Wang, Chunqiang; Li, Chunjin; Zhou, Xu

    2015-10-01

    Ovarian follicular cysts are anovulatory follicular structures that have been identified in sows and are known to cause infertility. The pathogenesis of follicular cysts remains poorly understood. Hormones play key roles in the formation and persistence of cysts. The hormone inhibin is a member of the TGF-β superfamily and is named for its negative regulation of FSH, another hormone that controls follicular recruitment and growth. In the present study, 48 sows with follicular cysts and 60 normal sows with no cysts were screened for mutations in the inhibin-α gene to examine the association of inhibin-α gene polymorphisms with the presence of follicular cysts. The results show that the c.-42G>A and c.3222G>A polymorphisms are significantly associated with follicular cysts and that sows with c.-42GG and c.3222GG genotypes have lower risk of developing cysts. Our findings may provide novel biological biomarkers and promising gene therapy candidates for follicular cyst formation in sows, which would greatly benefit pig breeding programs. PMID:26208435

  15. Clonidine-stimulated growth hormone concentrations (cut-off values) measured by immunochemiluminescent assay (ICMA) in children and adolescents with short stature

    PubMed Central

    de Fátima Borges, Maria; Teixeira, Flávia Carolina Cândida; Feltrin, Aline Karin; Ribeiro, Karina Alvarenga; Nascentes, Gabriel Antonio Nogueira; Resende, Elisabete Aparecida Mantovani Rodrigues; Ferreira, Beatriz Pires; Silva, Adriana Paula; Palhares, Heloísa Marcelina Cunha

    2016-01-01

    OBJECTIVES: To establish cut-off values for growth hormone concentrations using clonidine as a secretagogue and an immunochemiluminescent assay as the method of measurement and to analyze the response time as well as the influence of gender, nutritional status and pubertal stage. METHODS: A total of 225 tests were performed in 3 patient groups, categorized as group 1 (normal), group 2 (idiopathic short stature) and group 3 (growth hormone deficiency). Among the 199 disease-free individuals, 138 were prepubertal, and 61 were pubertal. Clonidine (0.1 mg/m2) was orally administered, and the growth hormone level was measured by immunochemiluminescent assay. The growth hormone peak and the difference between the growth hormone peak and the baseline level were then analyzed. Statistical analyses were performed using Student's t-test or the Mann-Whitney test and Kruskal-Wallis test followed by Dunn's post hoc test. Cut-off values were determined using a receiver operating characteristic curve. RESULTS: Group 1 and group 2 had no difference in growth hormone peak, gender, body mass index standard deviation score, or pubertal stage. Group 3 exhibited a significantly lower growth hormone peak than the other groups did. The receiver operating characteristic curve demonstrated that growth hormone concentrations ≥ 3.0 ng/mL defined responsiveness to clonidine. In total, 3.02% of individuals in group 1 and group 2 were considered false positive, i.e., these children lacked growth hormone deficiency and had a peak below 3.0 ng/mL. CONCLUSION: Clonidine-stimulated growth hormone concentrations ≥3 ng/mL, as measured by immunochemiluminescent assay, suggest responsiveness to the stimulus regardless of gender, body mass index standard deviation score or pubertal stage. PMID:27166774

  16. Ca2+-Activated K+ Channels in Gonadotropin-Releasing Hormone-Stimulated Mouse Gonadotrophs

    PubMed Central

    Waring, Dennis W.; Turgeon, Judith L.

    2009-01-01

    GnRH receptor activation elicits release of intracellular Ca2+, which leads to secretion and also activates Ca2+-activated ion channels underlying membrane voltage changes. The predominant Ca2+-activated ion channels in rat and mouse gonadotrophs are Ca2+-activated K+ channels. To establish the temporal relationship between GnRH-induced changes in intracellular [Ca2+] ([Ca2+]i) and membrane current (Im), and to identify specific Ca2+-activated K+ channels linking GnRH-induced increase in [Ca2+]i to changes in plasma membrane electrical activity, we used single female mouse gonadotrophs in the perforated patch configuration of the patch-clamp technique, which preserves signaling pathways. Simultaneous measurement of [Ca2+]i and Im in voltage-clamped gonadotrophs revealed that GnRH stimulates an increase in [Ca2+]i that precedes outward Im, and that activates two kinetically distinct currents identified, using specific toxin inhibitors, as small conductance Ca2+-activated K+ (SK) current (ISK) and large (big) conductance voltage- and Ca2+-activated K+ (BK) current (IBK). We show that the apamin-sensitive current has an IC50 of 69 pM, consistent with the SK2 channel subtype and confirmed by immunocytochemistry. The magnitude of the SK current response to GnRH was attenuated by 17β-estradiol (E2) pretreatment. Iberiotoxin, an inhibitor of BK channels, completely blocked the residual apamin-insensitive outward Im, substantiating that IBK is a component of the GnRH-induced outward Im. In contrast to its suppression of ISK, E2 pretreatment augmented peak IBK. SK or BK channel inhibition modulated GnRH-stimulated LH secretion, implicating a role for these channels in gonadotroph function. In summary, in mouse gonadotrophs the GnRH-stimulated increase in [Ca2+]i activates ISK and IBK, which are differentially regulated by E2 and which may be targets for E2 positive feedback in LH secretion. PMID:19106218

  17. Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

    PubMed

    Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-07-20

    The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist. PMID:27135265

  18. CXCL10/CXCR3 signaling mediates inhibitory action by interferon-gamma on CRF-stimulated adrenocorticotropic hormone (ACTH) release.

    PubMed

    Horiguchi, Kotaro; Fujiwara, Ken; Tsukada, Takehiro; Yoshida, Saishu; Higuchi, Masashi; Tateno, Kozue; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Yashiro, Takashi; Kato, Takako; Kato, Yukio

    2016-05-01

    Secretion of hormones by the anterior pituitary gland can be stimulated or inhibited by paracrine factors that are produced during inflammatory reactions. The inflammation cytokine interferon-gamma (IFN-γ) is known to inhibit corticotropin-releasing factor (CRF)-stimulated adrenocorticotropin (ACTH) release but its signaling mechanism is not yet known. Using rat anterior pituitary, we previously demonstrated that the CXC chemokine ligand 10 (CXCL10), known as interferon-γ (IFN-γ) inducible protein 10 kDa, is expressed in dendritic cell-like S100β protein-positive (DC-like S100β-positive) cells and that its receptor CXCR3 is expressed in ACTH-producing cells. DC-like S100β-positive cells are a subpopulation of folliculo-stellate cells in the anterior pituitary. In the present study, we examine whether CXCL10/CXCR3 signaling between DC-like S100β-positive cells and ACTH-producing cells mediates inhibition of CRF-activated ACTH-release by IFN-γ, using a CXCR3 antagonist in the primary pituitary cell culture. We found that IFN-γ up-regulated Cxcl10 expression via JAK/STAT signaling and proopiomelanocortin (Pomc) expression, while we reconfirmed that IFN-γ inhibits CRF-stimulated ACTH-release. Next, we used a CXCR3 agonist in primary culture to analyze whether CXCL10 induces Pomc-expression and ACTH-release using a CXCR3 agonist in the primary culture. The CXCR3 agonist significantly stimulated Pomc-expression and inhibited CRF-induced ACTH-release, while ACTH-release in the absence of CRF did not change. Thus, the present study leads us to an assumption that CXCL10/CXCR3 signaling mediates inhibition of the CRF-stimulated ACTH-release by IFN-γ. Our findings bring us to an assumption that CXCL10 from DC-like S100β-positive cells acts as a local modulator of ACTH-release during inflammation. PMID:26572542

  19. Growth Hormone

    MedlinePlus

    ... the dose of glucose. Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1) . ... regular intervals for years afterward to monitor GH production and to detect tumor recurrence. Other blood tests ...

  20. Genetically Determined Dosage of Follicle-Stimulating Hormone (FSH) Affects Male Reproductive Parameters

    PubMed Central

    Grigorova, Marina; Punab, Margus; Ẑilaitienė, Birutė; Erenpreiss, Juris; Ausmees, Kristo; Matuleviĉius, Valentinas; Tsarev, Igor; Jørgensen, Niels

    2011-01-01

    Context: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, −211 bp from the mRNA start) and significantly reduced male serum FSH. Objective: In the current study, the T-allele carriers of the FSHB −211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. Design and Subjects: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. Results: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10−6; T-allele effect, −0.41 IU/liter), inhibin-B (P = 2.16 × 10−3; T-allele effect, −14.67 pg/ml), and total testosterone (P = 9.30 × 10−3; T-allele effect, −1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10−4; TT genotype effect, −9.47 ml) and increased serum LH (P = 2.25 × 10−2; TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. Conclusion: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential. PMID:21733993

  1. Association Between Autoantibodies Against Thyroid Stimulating Hormone Receptor and Thyroid Diseases

    PubMed Central

    Latifi-Pupovci, Hatixhe

    2014-01-01

    Aim: The aim of this study is to determine the relationship between TRAb and different diseases. The highest percentage of increased TRAb levels can be found at patients with Graves’ diseases. Material and methods: Study was performed in 70 patients, grouped in three groups, and 14 persons who based on the clinical status and the levels of thyroid hormones do not have any thyroid disease. The TRAb levels has been determined in patients with Graves’ disease (N=40), Hashimoto’s disease (N=15), Plummer’s disease (N=15) and the control group (N=14). Results: The highest mean TRAb levels exist in patients with Graves’ disease. There exists a positive correlation between TRAb levels and T3, and T4, while there is no correlation between TSH and TRAb levels in patients with Graves’ disease,. On the other hand, the correlation between TRAb and T3 and T4 in patients with Hashimoto’s diseases and Plummers disease was shown to be positive, but of a low levels.

  2. AGE-RELATED ALTERATIONS IN THE STIMULATED RELEASE IN VITRO OF CATECHOLAMINES AND LUTEINIZING HORMONE-RELEASING HORMONE FROM THE MALE RAT HYPOTHALAMUS

    EPA Science Inventory

    Using an in vitro perifusion system, the present study investigated the possibility that alterations in catecholamine and luteinizing hormone-releasing hormone (LHRH) secretion from the male rat mediobasal hypothalamus are present during the period of middle-age. The results indi...

  3. A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.

    PubMed

    de Roux, N; Polak, M; Couet, J; Leger, J; Czernichow, P; Milgrom, E; Misrahi, M

    1996-06-01

    Until recently, neonatal hyperthyroidism has been considered to be related to the transplacental passage of thyroid-stimulating Ig present in the serum of the mother. We report here the case of a newborn who presented with severe hyperthyroidism, diffuse goiter, and important ocular signs (eyelid retraction and possibly proptosis). However, the absence of thyroid pathology in the parents and the lack of antithyroid antibodies in the mother and in the patient led us to suspect a nonimmune aetiology. Direct genomic sequencing of the last exon of the TSH receptor in the patient revealed a T-->C transversion yielding to a Met453-->Thr heterozygous substitution in the second transmembrane domain of the receptor. The mutation was absent in both parents. Eukaryotic expression analysis in COS-7 cells yielded a mutated receptor that produced constitutive activation of adenylate cyclase without enhancement of phospholipase C activity. PMID:8964822

  4. Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus.

    PubMed

    Burel, Delphine; Li, Jian Hua; Do-Rego, Jean-Luc; Wang, Ai Fen; Luu-The, Van; Pelletier, Georges; Tillet, Yves; Taragnat, Catherine; Kwon, Hyuk Bang; Seong, Jae Young; Vaudry, Hubert

    2013-06-01

    The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of Δ(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior preoptic area, two hypothalamic regions that are richly innervated by GnRH1-containing fibers. This observation suggests that GnRH1 may regulate the formation of sulfated neurosteroids to control sexual activity. Double labeling of frog brain slices with HST and GnRH1 antibodies revealed that GnRH1-immunoreactive fibers are located in close vicinity of HST-positive neurons. The cDNAs encoding 3 GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned from the frog brain. RT-PCR analyses revealed that riGnRHR-1 is strongly expressed in the hypothalamus and the pituitary whereas riGnRHR-2 and -3 are primarily expressed in the brain. In situ hybridization histochemistry indicated that GnRHR-1 and GnRHR-3 mRNAs are particularly abundant in preoptic area and magnocellular nucleus whereas the concentration of GnRHR-2 mRNA in these 2 nuclei is much lower. Pulse-chase experiments using tritiated Δ(5)P and DHEA as steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate as a sulfonate moiety donor, showed that GnRH1 stimulates, in a dose-dependent manner, the biosynthesis of Δ(5)PS and DHEAS in frog diencephalic explants. Because Δ(5)PS and DHEAS, like GnRH, stimulate sexual activity, our data strongly suggest that some of the behavioral effects of GnRH could be mediated via the modulation of sulfated neurosteroid production. PMID:23554453

  5. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I.

    PubMed

    Zoidis, E; Ghirlanda-Keller, C; Schmid, C

    2011-02-01

    Insulin and parathyroid hormone (PTH) regulate glucose metabolism in bone cells. In order to differentiate between the effects of these hormones and to compare the potency of insulin with that of insulin-like growth factor (IGF) I, we treated rat bone-derived osteoblastic (PyMS) cells for different time periods and at different concentrations with insulin, IGF I, or PTH, and measured [1-(14)C]-2-deoxy-D-glucose (2DG) uptake and incorporation of D-[U-(14)C] glucose into glycogen. 2DG uptake was Na-independent with an apparent affinity constant (K (M)) of ~2 mmol/l. Expression of the high affinity glucose transporters (GLUT), GLUT1 and GLUT3 but not of GLUT4, was found by Northern and Western analysis. Similar to the findings with primary rat osteoblasts, but distinct from those in rat fibroblasts, 2DG uptake and glycogen synthesis were increased in this cell line after exposure to low concentrations (0.1 nmol/l and above) of PTH. IGF I at low doses (0.3 nmol/l and above) or insulin at higher doses (1 nmol/l and above) stimulated 2DG uptake and [(3)H] thymidine incorporation into DNA. 2DG transport was enhanced already after 30 min of IGF I treatment whereas the effect of PTH became significant after 6 h. It is concluded that IGF I rather than insulin may be a physiological regulator of 2DG transport and glycogen synthesis in osteoblasts. PMID:21076856

  6. Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica.

    PubMed

    Kim, Dae-Jung; Park, Chae-Won; Kim, Dong-Wan; Park, Hong-Kyu; Byambaragchaa, Munkhzaya; Lee, Nam-Sil; Hong, Sun-Mee; Seo, Mi-Young; Kang, Myung-Hwa; Min, Kwan-Sik

    2016-07-01

    We prepared monoclonal antibodies (mAbs) against a recombinant tethered follicle-stimulating hormone (rec-FSH) from Japanese eel Anguilla japonica that was produced in Escherichia coli. Positive hybridomas (clones eFA-C5, eFA-C10, eFA-C11, eFA-C12, eFA-C13, and eFB-C14) were selected by using the eel FSH antigen in ELISA, and anti-eel FSH mAbs were purified from culture supernatants by performing affinity chromatography. Three of the 6mAbs were characterized and their isotypes were identified as IgG2b (eFA-C5 and eFA-C11) and IgG1 (eFB-C14). In western blotting assays, the mAbs recognized the antigen as a 24.3-kDa band, and further detected bands of 34 and 32kDa in the supernatants of CHO cells transfected with cDNA encoding tethered eel FSHβ/α and LHβ/α, respectively. PNase F-mediated deglycosylation of the recombinant proteins resulted in a drastic reduction in their molecular weight, to 7-9kDa. The mAbs eFA-C5 and eFA-C11 recognized the eel FSHα-subunit that is commonly encoded among glycoprotein hormones, whereas eFB-C14 recognized the eel FSHβ-subunit, and immunohistochemical analysis revealed that the staining by these mAbs was specifically localized in the eel pituitary. We also established an ELISA system for detecting rec-tethered FSHβ/α and LHβ/α produced from CHO cell lines. Measurement of biological activities in vitro revealed that only weak activity of rec-FSHβ/α was detected. The activity of rec-LHβ/α was found to be increased in a dose-dependent manner for eel oocyte maturation. PMID:27174750

  7. Inherent Suppression of Thyroid Stimulating Hormone in Newly Diagnosed Dyslipidemic Patients – Indication for Use of Thyromimetics?

    PubMed Central

    Udupa, Sridevi V.; D’Souza, Vivian; Udupa, Vinit A.

    2014-01-01

    Background: Dyslipidemia triggers a sequel of metabolic derangements such as insulin resistance, hyperglycemia and oxidative stress via vicious cycle. Dyslipidemia is characterised by elevation of plasma cholesterol, triglycerides (TGs), or both, or a low level of high-density lipoprotein (HDL) which in turn can progress to atherosclerosis a forerunner for ischemic heart disease (IHD). Dyslipidemia is seen even in subclinical hypothyroid patients. Objectives: The aim of the study was to look for thyroid & glycemic abnormalities in dyslipidemic patients and compare it with euthyroid, normolipidemic group. Materials and Methods: Thirty primarily dyslipidemic patients and 30 euthyroid normolipidemic subjects aged 25-55 years were tested for fasting plasma glucose (FPG), fructosamine, lipid profile, thyroid hormones - T3, T4 and thyroid stimulating hormone (TSH). The values were compared with those of age matched euthyroid normolipidemic control group. Results: The dyslipidemic pool showed small but significant decrease in the TSH levels with comparable T3, T4 levels as compared to euthyroid group. The group also had significantly higher FPG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) levels and lower high density lipoprotein (HDL) levels as compared to the euthyroid normolipidemic group. The plasma fructosamine levels were similar in both the groups. The observed results reflected a picture of subclinical hyperthyroidism in dyslipidemic patients. Conclusion: The observations of the present study preclude a need to assess the thyroid status in patients of primary dyslipidemia as both conditions per se have an increased risk of cardio vascular diseases. A subclinical hyperthyroid state may essentially be helpful in maintaining the lipid metabolism. The prevailing mild hyperthyroid status also makes it important to reconsider the accuracy of long term glycemic indicators like fructosamine and possibly glycated haemoglobin in these patients

  8. Thyroid hormone stimulates Na-K-ATPase activity and its plasma membrane insertion in rat alveolar epithelial cells.

    PubMed

    Lei, Jianxun; Nowbar, Sogol; Mariash, Cary N; Ingbar, David H

    2003-09-01

    Na-K-ATPase protein is critical for maintaining cellular ion gradients and volume and for transepithelial ion transport in kidney and lung. Thyroid hormone, 3,3',5-triiodo-l-thyronine (T3), given for 2 days to adult rats, increases alveolar fluid resorption by 65%, but the mechanism is undefined. We tested the hypothesis that T3 stimulates Na-K-ATPase in adult rat alveolar epithelial cells (AEC), including primary rat alveolar type II (ATII) cells, and determined mechanisms of the T3 effect on the Na-KATPase enzyme using two adult rat AEC cell lines (MP48 and RLE-6TN). T3 at 10-8 and 10-5 M increased significantly hydrolytic activity of Na-K-ATPase in primary ATII cells and both AEC cell lines. The increased activity was dose dependent in the cell lines (10-9-10-4 M) and was detected within 30 min and peaked at 6 h. Maximal increases in Na-K-ATPase activity were twofold in MP48 and RLE-6TN cells at pharmacological T3 of 10-5 and 10-4 M, respectively, but increases were statistically significant at physiological T3 as low as 10-9 M. This effect was T3 specific, because reverse T3 (3,3',5'-triiodo-l-thyronine) at 10-9-10-4 M had no effect. The T3-induced increase in Na-K-ATPase hydrolytic activity was not blocked by actinomycin D. No significant change in mRNA and total cell protein levels of Na-K-ATPase were detected with 10-9-10-5 M T3 at 6 h. However, T3 increased cell surface expression of Na-K-ATPase alpha1- or beta1-subunit proteins by 1.7- and 2-fold, respectively, and increases in Na-K-ATPase activity and cell surface expression were abolished by brefeldin A. These data indicate that T3 specifically stimulates Na-K-ATPase activity in adult rat AEC. The upregulation involves translocation of Na-K-ATPase to plasma membrane, not increased gene transcription. These results suggest a novel nontranscriptional mechanism for regulation of Na-K-ATPase by thyroid hormone. PMID:12740220

  9. Inhibition of autophagy stimulate molecular iodine-induced apoptosis in hormone independent breast tumors

    SciTech Connect

    Singh, Preeti; Godbole, Madan; Rao, Geeta; Annarao, Sanjay; Mitra, Kalyan; Roy, Raja; Ingle, Arvind; Agarwal, Gaurav; Tiwari, Swasti

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Molecular iodine (I{sub 2}) causes non-apoptotic cell death in MDA-MB231 breast tumor cells. Black-Right-Pointing-Pointer Autophagy is activated as a survival mechanism in response to I{sub 2} in MDA-MB231. Black-Right-Pointing-Pointer Autophagy inhibition sensitizes tumor cells to I{sub 2}-induced apoptotic cell death. Black-Right-Pointing-Pointer Autophagy inhibitor potentiates apoptosis and tumor regressive effects of I{sub 2} in mice. -- Abstract: Estrogen receptor negative (ER{sup -ve}) and p53 mutant breast tumors are highly aggressive and have fewer treatment options. Previously, we showed that molecular Iodine (I{sub 2}) induces apoptosis in hormone responsive MCF-7 breast cancer cells, and non-apoptotic cell death in ER{sup -ve}-p53 mutant MDA-MB231 cells (Shrivastava, 2006). Here we show that I{sub 2} (3 {mu}M) treatment enhanced the features of autophagy in MDA-MB231 cells. Since autophagy is a cell survival response to most anti-cancer therapies, we used both in vitro and in vivo systems to determine whether ER{sup -ve} mammary tumors could be sensitized to I{sub 2}-induced apoptosis by inhibiting autophagy. Autophagy inhibition with chloroquine (CQ) and inhibitors for PI3K (3MA, LY294002) and H+/ATPase (baflomycin) resulted in enhanced cell death in I{sub 2} treated MDA-MB231 cells. Further, CQ (20 {mu}M) in combination with I{sub 2}, showed apoptotic features such as increased sub-G1 fraction ({approx}5-fold), expression of cleaved caspase-9 and -3 compared to I{sub 2} treatment alone. Flowcytometry of I{sub 2} and CQ co-treated cells revealed increase in mitochondrial membrane permeability (p < 0.01) and translocation of cathepsin D activity to cytosol relative to I{sub 2} treatment. For in vivo studies ICRC mice were transplanted subcutaneously with MMTV-induced mammary tumors. A significant reduction in tumor volumes, as measured by MRI, was found in I{sub 2} and CQ co-treated mice relative to I{sub 2} or

  10. Vasoactive intestinal peptide enhanced aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone

    SciTech Connect

    George, F.W.; Ojeda, S.R.

    1987-08-01

    The authors have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of /sup 3/H/sub 2/O formed from (1..beta..-/sup 3/H)testosterone) is low prior to birth and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone, ovine luteinizing hormone, or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenouse cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation.

  11. Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA binding activity.

    PubMed Central

    Gouilleux, F; Pallard, C; Dusanter-Fourt, I; Wakao, H; Haldosen, L A; Norstedt, G; Levy, D; Groner, B

    1995-01-01

    The molecular components which mediate cytokine signaling from the cell membrane to the nucleus were studied. Upon the interaction of cytokines with their receptors, members of the janus kinase (Jak) family of cytoplasmic protein tyrosine kinases and of the signal transducers and activators of transcription (Stat) family of transcription factors are activated through tyrosine phosphorylation. It has been suggested that the Stat proteins are substrates of the Jak protein tyrosine kinases. MGF-Stat5 is a member of the Stat family which has been found to confer the prolactin response. MGF-Stat5 can be phosphorylated and activated in its DNA binding activity by Jak2. The activation of MGF-Stat5 is not restricted to prolactin. Erythropoietin (EPO) and growth hormone (GH) stimulate the DNA binding activity of MGF-Stat5 in COS cells transfected with vectors encoding EPO receptor and MGF-Stat5 or vectors encoding GH receptor and MGF-Stat5. The activation of DNA binding by prolactin, EPO and GH requires the phosphorylation of tyrosine residue 694 of MGF-Stat5. The transcriptional induction of a beta-casein promoter luciferase construct in transiently transfected COS cells is specific for the prolactin activation of MGF-Stat5; it is not observed in EPO- and GH-treated cells. In the UT7 human hematopoietic cell line, EPO and granulocyte-macrophage colony stimulating factor activate the DNA binding activity of a factor closely related to MGF-Stat5 with respect to its immunological reactivity, DNA binding specificity and molecular weight. These results suggest that MGF-Stat5 regulates physiological processes in mammary epithelial cells, as well as in hematopoietic cells.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:7744007

  12. Follicle Stimulating Hormone (FSH) Dosage Based on Body Weight Enhances Ovulatory Responses and Subsequent Embryo Production in Goats

    PubMed Central

    Rahman, M. R.; Rahman, M. M.; Wan Khadijah, W. E.; Abdullah, R. B.

    2014-01-01

    An experiment was conducted to evaluate the efficacy of porcine follicle stimulating hormone (pFSH) dosage based on body weight (BW) on ovarian responses of crossbred does. Thirty donor does were divided into 3 groups getting pFSH dosages of 3, 5, and 8 mg pFSH per kg BW, respectively, and were named as pFSH-3, pFSH-5 and pFSH-8, respectively. Estrus was synchronized by inserting a controlled internal drug release (CIDR) device and a single injection of prostaglandin F2α (PGF2α). The pFSH treatments were administered twice a day through 6 decreasing dosages (25, 25, 15, 15, 10, and 10% of total pFSH amount; decreasing daily). Ovarian responses were evaluated on Day 7 after CIDR removal. After CIDR removal, estrus was observed 3 times in a day and pFSH treatments were initiated at 2 days before the CIDR removal. All does in pFSH-5 and pFSH-8 showed estrus signs while half of the does in pFSH-3 showed estrus signs. No differences (p>0.05) were observed on the corpus luteum and total ovarian stimulation among the treatment groups, while total and transferable embryos were higher (p<0.05) in pFSH-5 (7.00 and 6.71) than pFSH-3 (3.00 and 2.80) and pFSH-8 (2.00 and 1.50), respectively. In conclusion, 5 mg pFSH per kg BW dosage gave a higher number of embryos than 3 and 8 mg pFSH per kg BW dosages. The results indicated that the dosage of pFSH based on BW is an important consideration for superovulation in goats. PMID:25178370

  13. Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs

    SciTech Connect

    Feyen, J.H.; van der Wilt, G.; Moonen, P.; Di Bon, A.; Nijweide, P.J.

    1984-12-01

    The effects of parathyroid hormone (PTH), dihydroxycholecalciferol (1,25-(OH)2 D3), thrombin, epidermal growth factor (EGF) and 12-o-tetradecanoylphorbol-13-acetate (PMA) on the biosynthesis and release of arachidonic acid metabolites were studied in primary cultures of osteoblast-like cells isolated from 18-day-old chick embryo calvaria. Cells were labelled with (/sup 14/C)-arachidonic acid for 30 h. The radioactive eicosanoids were extracted from the cell culture media after a further 30 h stimulation period and analysed on a PRP-1 column by HPLC. The radioactive products were characterized by co-elution of (/sup 3/H) standard prostanoids. Osteoblasts showed a basal release of the prostanoids 6-keto-PGF1 alpha, TXB2, PGF2 alpha, PGE2, PGD2 and PGB2, the latter being the most abundant one. Indomethacin (10(-5) M) effectively inhibited the basal release, but not that of an as yet unidentified compound. The release of prostanoids was stimulated by PTH (2 U/ml), thrombin (0.4 NIH/ml), EGF (50 ng/ml) and PMA (25 ng/ml), the latter being by far the most potent one. 1,25-(OH)2D3 was found to slightly inhibit the prostanoid release. These results indicate: (1) primary cultures of osteoblasts synthesize several prostaglandins, thromboxane B2 and one unidentified product. (2) the action on bone of PTH and the various drugs tested may be, at least partly, mediated by an increased prostaglandin production by osteoblasts. Clearly this does not apply to 1,25-(OH)2D3.

  14. Follicle-stimulating hormone increases the intramuscular fat content and expression of lipid biosynthesis genes in chicken breast muscle*

    PubMed Central

    Cui, Xiao-yan; Li, Ying-ying; Liu, Ran-ran; Zhao, Gui-ping; Zheng, Mai-qing; Li, Qing-he; Wen, Jie

    2016-01-01

    Intramuscular fat (IMF) is a crucial factor in the quality of chicken meat. The genetic basis underlying it is complex. Follicle-stimulating hormone (FSH), well-known as an effector in reproductive tissues, was recently discovered to stimulate abdominal fat accumulation in chicken. The effect of FSH on IMF accumulation and the underlying molecular regulatory mechanisms controlling both IMF and abdominal fat deposition in vivo are largely unknown. In this study, two groups of chickens were treated with chicken FSH or a placebo. The lipid content of breast muscle, abdominal fat volume, and serum concentrations of FSH were examined. Related genes implicated in breast muscle and abdominal fat accumulation were also investigated. Compared to the control group, the triglyceride (TG) content of breast muscle and the percentage of abdominal fat in FSH-treated chickens were significantly increased by 64.9% and 56.5% (P<0.01), respectively. The FSH content in the serum of FSH-treated chickens was 2.1 times than that of control chickens (P<0.01). Results from quantitative real-time polymerase chain reaction (qRT-PCR) assays showed that relative expression levels of fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerol acyltransferase 2 (DGAT2), adipocyte fatty acid binding protein (A-FABP), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly upregulated in breast muscle following FSH treatment (P<0.01). Treatment with FSH also significantly increased relative expression levels of FAS, LPL, DGAT2, A-FABP, and PPARγ in abdominal fat tissue (P<0.05). The results of principal component analysis (PCA) for gene expression (breast muscle and abdominal fat) showed that the control and FSH treatment groups were well separated, which indicated the reliability of the data. This study demonstrates that FSH plays an important role in IMF accumulation in female chickens, which likely involves the regulation of biosynthesis genes related to lipid

  15. Effects of 3, 5, 3'-triiodothyronine (t3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells.

    PubMed

    Zhang, Cheng; Guo, Li; Zhu, Baochang; Feng, Yun; Yu, Shangyu; An, Na; Wang, Xiaoxia

    2013-10-31

    Thyroid hormone (TH) is important for normal reproductive functions and dysregulation of TH support is associated with reproductive disorders. We have previously reported that 3,5,3'-triiodothyronine (T₃) increases follicle stimulating hormone (FSH)-induced preantral follicle growth in vitro. Interaction of hormones with apoptosis and proliferation of granulosa cells is poorly understood. The present study investigated the role and the mechanism of T₃ and/or FSH on granulosa cell apoptosis and proliferation. Granulosa cells harvested from DES-primed immature rats were exposed to T₃ (1 nM) and/or FSH (100 ng/ml) for 24-48 h. We demonstrated by TUNEL assays that the hormones prevented cells from C8-ceramide-induced apoptosis. The Src/PI3K/Akt pathway was involved in the regulation of granulosa cell survival. While ineffective alone, T₃ significantly enhanced the proliferating cell nuclear antigen (PCNA) content of FSH-induced granulosa cells, consistent with the cell number pattern after treatment. Moreover, the action of the hormones on cell proliferation was also shown to be mediated by the Src/PI3K/Akt pathway. Taken together, these results suggest that T₃ potentiates the cell survival action of FSH through inhibiting cell apoptosis and promoting cell proliferation. Moreover, the protective and survival effects of hormones are mediated by the activation of Src/PI3K/Akt pathway. PMID:24032715

  16. Variability in Thyroid-Stimulating Hormone Suppression by Human Chronic Gonadotropin during Early Pregnancy

    PubMed Central

    Haddow, James E.; McClain, Monica R.; Lambert-Messerlian, Geralyn; Palomaki, Glenn E.; Canick, Jacob A.; Cleary-Goldman, Jane; Malone, Fergal D.; Porter, T. Flint; Nyberg, David A.; Bernstein, Peter; D'Alton, Mary E.

    2008-01-01

    Objective: The objective of the study was to further explore relationships between human chorionic gonadotropin (hCG), TSH, and free T4 in pregnant women at 11 through 18 wk gestation. Study Design: The design of the study was to analyze hCG in comparison with TSH and free T4, in paired first- and second-trimester sera from 9562 women in the First and Second Trimester Evaluation of Risk for Fetal Aneuploidy trial study. Results: hCG is strongly correlated with body mass index, smoking, and gravidity. Correlations with selected maternal covariates also exist for TSH and free T4. As hCG deciles increase, body mass index and percent of women who smoke both decrease, whereas the percent of primigravid women increases (P < 0.0001). hCG/TSH correlations are weak in both trimesters (r2 = 0.03 and r2 = 0.02). TSH concentrations at the 25th and fifth centiles become sharply lower at higher hCG levels, whereas 50th centile and above TSH concentrations are only slightly lower. hCG/free T4 correlations are weak in both trimesters (r2 = 0.06 and r2 = 0.003). At 11–13 wk gestation, free T4 concentrations rise uniformly at all centiles, as hCG increases (test for trend, P < 0.0001), but not at 15–18 wk gestation. Multivariate analyses with TSH and free T4 as dependent variables and selected maternal covariates and hCG as independent variables do not alter these observations. Conclusions: In early pregnancy, a woman’s centile TSH level appears to determine susceptibility to the TSH being suppressed at any given hCG level, suggesting that hCG itself may be the primary analyte responsible for stimulating the thyroid gland. hCG affects lower centile TSH values disproportionately. PMID:18544616

  17. Corifollitropin alfa versus recombinant follicle-stimulating hormone: an individual patient data meta-analysis.

    PubMed

    Griesinger, Georg; Boostanfar, Robert; Gordon, Keith; Gates, Davis; McCrary Sisk, Christine; Stegmann, Barbara J

    2016-07-01

    A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of corifollitropin alfa versus rFSH: Engage (150 µg corifollitropin alfa n = 756; 200 IU rFSH n = 750), Ensure (100 µg corifollitropin alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 µg corifollitropin alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or ≤60 kg (Ensure), or women aged 35-42 years and body weight ≥50 kg (Pursue), received a single injection (100 µg or 150 µg) of corifollitropin alfa (based on body weight and age) or daily rFSH. The difference (corifollitropin alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of corifollitropin alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH. PMID:27178762

  18. Misfolding Ectodomain Mutations of the Lutropin Receptor Increase Efficacy of Hormone Stimulation.

    PubMed

    Charmandari, E; Guan, R; Zhang, M; Silveira, L G; Fan, Q R; Chrousos, G P; Sertedaki, A C; Latronico, A C; Segaloff, D L

    2016-01-01

    We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention. However, we made the unusual discovery that the intrinsic efficacy for agonist-stimulated cAMP in the reduced numbers of receptors on the cell surface was greatly increased relative to the same low number of cell surface wild-type receptor. Remarkably, this appears to be a general attribute of misfolding mutations in the ectodomains, but not serpentine domains, of the gonadotropin receptors. These findings suggest that there must be a common, shared mechanism by which disparate mutations in the ectodomain that cause misfolding and therefore reduced cell surface expression concomitantly confer increased agonist efficacy to those receptor mutants on the cell surface. Our data further suggest that, due to their increased agonist efficacy, extremely small changes in cell surface expression of misfolded ectodomain mutants cause larger than expected alterations in the cellular response to agonist. Therefore, for inactivating LHCGR mutations causing ectodomain misfolding, the numbers of cell surface mutant receptors on fetal Leydig cells of 46,XY individuals exert a more exquisite effect on the relative severity of the clinical phenotypes than already appreciated. PMID:26554443

  19. Response to hypogravity of normal in vitro cultured follicular cells from thyroid

    NASA Astrophysics Data System (ADS)

    Meli, Antonella; Perrella, Giuseppina; Curcio, Francesco; Saverio, F.; Impiombato, Ambesi

    Aim of this investigation is the study of molecular modifications occurring in differentiated mammalian cells exposed to gravitational changes. The test system chosen is a well characterized clone of differentiated, normal thyroid follicular cells (FRTL5) in long-term culture. As a follow-up to our recent experiment performed during the MASER-7 sounding rocket mission, flown for European Space Agency by Swedish Space Corporation in May 1996, we evaluated FRTL5 cells responses to Thyroid Stimulating Hormone dependent cAMP production under acute hypogravity conditions obtained in a fast rotating clinostat. Following this approach, we evaluated the FRTL5 cells response to TSH under microgravity conditions in order to optimize experimental tools and strategies in preparation to, and in between real flight missions.

  20. Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age

    PubMed Central

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

    2015-01-01

    The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4–6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45–15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence—third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration—a surrogate marker for MID—was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10–15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children. PMID:26540070

  1. Corticotropin Releasing Hormone and Urocortin 3 Stimulate Vascular Endothelial Growth Factor Expression through the cAMP/CREB Pathway.

    PubMed

    Rhee, Sang Hoon; Ma, Elise L; Lee, Yunna; Taché, Yvette; Pothoulakis, Charalabos; Im, Eunok

    2015-10-23

    Colonic epithelium is the first line of defense against various pathological offenses in the gut. Previous studies have shown that the peptides of the corticotropin-releasing hormone (CRH) family modulate vascular endothelial growth factor (VEGF)-A production in other cells. Here we sought to investigate whether CRH and urocortin (Ucn) 3 regulate VEGF-A secretion in colonocytes through CRH receptors and to elucidate the underlying mechanism of action. CRH and Ucn 3 significantly increased the expression levels of VEGF-A mRNA and protein through CRH receptor 1 and 2, respectively, in human colonic epithelial cells and primary mouse intestinal epithelial cells. Underlying mechanisms involve activation of adenylyl cyclase with subsequent increase of intracellular cAMP level and increased DNA binding activity of transcription factor CREB on VEGF-A promoter region. Finally, genetic deficiency of CREB decreased intestinal inflammation and VEGF-A expression in a dextran sodium sulfate-induced colitis model. These results show that activation of CRH receptors by CRH ligands stimulates VEGF-A expression in intestinal epithelial cells through the cAMP/CREB pathway. Since VEGF-A boosts inflammatory responses through angiogenesis, these data suggest that CREB may be a key effector of CRH and Ucn 3-dependent inflammatory angiogenesis. PMID:26350463

  2. Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

    NASA Astrophysics Data System (ADS)

    Zhou, Wen; Håkansson, Kristina

    2013-11-01

    Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

  3. The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes

    PubMed Central

    Ryu, Sunhyo; Johnson, Andrew; Park, Yoonkyung; Kim, Beomjoon; Norris, David; Armstrong, Cheryl A.; Song, Peter I.

    2015-01-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). α-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-κB nuclear translocation in HK cells. The inhibitory effect of α-MSH was blocked by agouti signaling protein (ASP), an α-MSH receptor-1 antagonist. To investigate the mechanism of this response in more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized in these studies. The α-MSH suppressive effect on IL-8 production and NF-κB transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that α-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of α-MSH in normal human keratinocytes. PMID:26309029

  4. Wide-range quantification of human thyroid-stimulating hormone using gold-nanopatterned single-molecule sandwich immunoassay chip.

    PubMed

    Lee, Seungah; Kang, Seong Ho

    2012-09-15

    We performed wide-range quantification of human thyroid-stimulating hormone (hTSH) using a gold nano-patterned sandwich immunoassay chip. Objective-type total internal reflection fluorescence microscopy (TIRFM) was used to detect hTSH at the single-molecule level. A gold spot with a diameter of 100 nm on a 10-mm square glass substrate was fabricated by electron beam nanolithography. When hTSH bound to antibodies conjugated to each 100-nm gold spot, there was an increase in the relative fluorescent intensity (RFI). The detection limit of this "TSH-nanoarray chip" was 360 zM (equivalent to five molecules), which demonstrated that a TSH-nanoarray chip could be used for detection at the single-molecule level. A linear response was observed over a wide dynamic range (from 360 zM to 36 pM, R=0.9812) without a fluorescence quenching effect. A significant enhancement in the sensitivity (~12,000-fold) was achieved with the 100-nm gold nano-patterned chip compared with results obtained using a traditional chemiluminescence immunoassay for the evaluation of TSH in human serum. PMID:22967658

  5. Weight loss results in a small decrease in follicle stimulating hormone in overweight glucose-intolerant postmenopausal women

    PubMed Central

    Kim, Catherine; Randolph, John F.; Golden, Sherita H.; Labrie, Fernand; Kong, Shengchun; Nan, Bin; Barrett-Connor, Elizabeth

    2014-01-01

    Structured Abstract Objective To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. Design and Methods Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n=382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, metformin 850 mg, or placebo administered twice a day. Results Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, p<0.01). Increases in FSH were correlated with decreases in weight (r=-0.165, p<0.01) and E2 (r=-0.464, p<0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. Conclusions Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways. PMID:25294746

  6. The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes.

    PubMed

    Ryu, Sunhyo; Johnson, Andrew; Park, Yoonkyung; Kim, Beomjoon; Norris, David; Armstrong, Cheryl A; Song, Peter I

    2015-01-01

    Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). α-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-κB nuclear translocation in HK cells. The inhibitory effect of α-MSH was blocked by agouti signaling protein (ASP), an α-MSH receptor-1 antagonist. To investigate the mechanism of this response in more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized in these studies. The α-MSH suppressive effect on IL-8 production and NF-κB transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that α-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of α-MSH in normal human keratinocytes. PMID:26309029

  7. Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

    PubMed Central

    Zhou, Wen; Håkansson, Kristina

    2013-01-01

    Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information. PMID:23982932

  8. Effect of thyroid peroxidase antibodies on thyroid-stimulating hormone reference limits in a primarily Latina population

    PubMed Central

    Lee, Richard H; Spencer, Carole A; Montoro, Martin N; Aghajanian, Paola; Goodwin, T Murphy; Miller, Erin A; Petrovic, Ivana; Braverman, Lewis E; Mestman, Jorge H

    2009-01-01

    The aim of the paper is to determine the prevalence of thyroid peroxidase antibodies (TPOAb) and assess its effect on the thyroid-stimulating hormone (TSH) reference range during pregnancy in a primarily Latina population. Serum samples were collected from healthy pregnant women and non-pregnant controls. TSH reference ranges were calculated when TPOAb-positive patients were either included or excluded. A total of 134 pregnant women and 107 non-pregnant controls were recruited. Positive TPOAb titres were found in 23 (17.2%) of the 134 pregnant women, and in 14 (13.1%) of the 107 non-pregnant controls. When the TPOAb-positive women were included in the TSH analysis, the upper reference limit using two different methods was consistently higher: 0–2.2 fold in the non-pregnant women, 2.01–2.78 fold in the first trimester, 3.18–4.7 fold in the second and 1.05–1.42 fold in the third. The lower TSH reference limit was not affected by the inclusion of TPOAb-positive subjects. In conclusion, inclusion of TPOAb-positive patients results in higher upper reference limits during pregnancy.

  9. Neuropeptide Y and gamma-melanocyte stimulating hormone (γ-MSH) share a common pressor mechanism of action

    PubMed Central

    Gruber, Kenneth A.; Fan, Wei; Akerberg, Helena; Larhammar, Dan; Chee, Melissa J. S.; Colmers, William F.; Cone, Roger D.

    2009-01-01

    Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes both of these C-terminal motifs. We now present evidence that an antagonist with Y1 and RFamide receptor activity, BIBO3304, will attenuate the central cardiovascular effects of both gamma-melanocyte stimulating hormone (γ-MSH) and NPY. The use of synthetic melanocortin and NPY peptide analogs excluded an interaction with melanocortin or Y family receptors. We suggest that the anatomical convergence of NPY and melanocortin neurons on cardiovascular control centers may have pathophysiological implications through a common or similar RFamide receptor(s), much as they converge on other nuclei to coordinately control energy homeostasis. PMID:19363600

  10. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1989-02-01

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days.

  11. Regulation of the mesocorticolimbic and mesostriatal dopamine systems by α-melanocyte stimulating hormone and agouti-related protein.

    PubMed

    Roseberry, Aaron G; Stuhrman, Katherine; Dunigan, Anna I

    2015-09-01

    The melanocortin system of the hypothalamus, including the neuropeptides α-melanocyte stimulating hormone (αMSH) and agouti-related protein (AgRP), and their receptors, the melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), have been well-studied for their roles in the central control of feeding and body weight. In this review, we discuss the evidence demonstrating that αMSH and AgRP also act on the mesocorticolimbic and mesostriatal dopamine systems to regulate a wide variety of behaviors. In addition to the well described ability of αMSH to increase dopamine transmission and to increase grooming and rearing when injected directly into the ventral tegmental area, a growing body of evidence indicates that αMSH and AgRP can also act on dopamine pathways to regulate feeding and drug abuse, including reward-related behaviors toward food and drugs. Increasing our understanding of how αMSH and AgRP act on dopamine pathways to affect behavior may allow for identification of new strategies to combat disorders involving dysfunction of dopamine pathways, such as obesity and drug abuse. PMID:26116876

  12. The epidemiology of iodine-deficiency disorders in relation to goitrogenic factors and thyroid-stimulating-hormone regulation.

    PubMed

    Thilly, C H; Swennen, B; Bourdoux, P; Ntambue, K; Moreno-Reyes, R; Gillies, J; Vanderpas, J B

    1993-02-01

    In children aged 5-7 y from goiter-endemic areas in Ubangi, Zaire, and Ntcheu, Malawi, mean serum thyroxin (T4) concentrations were 53 +/- 49 vs 81 +/- 33 nmol/L (P < 0.05), and thyroid-stimulating hormone (TSH) values were 24.3 +/- 9.6 vs 4.5 +/- 3.3 mU/L respectively (P < 0.01); mean urinary iodine concentrations were 0.14 +/- 0.02 vs 0.09 +/- 0.02 mumol/L, and mean thiocyanate concentrations were 0.33 +/- 0.05 vs 0.17 +/- 0.05 nmol/L, respectively (P < 0.05). Mean serum selenium concentrations were 0.343 +/- 0.176 mumol/L in Ubangi and 0.437 +/- 0.178 mumol/L in Ntcheu (P < 0.05). In two groups of 11 adolescent girls from Ubangi, the mean values for excretion of urinary iodine were 1.31 +/- 0.14 and 0.58 +/- 0.17 mumol/L (P < 0.05) after a meal of cassava or a control meal of rice, respectively. In euthyroid subjects from Ubangi, mean serum TSH for a given serum T4 was approximately twice as high for children aged < 15 y than for those aged 16-25 y. The high frequency of myxedematous cretins observed in Ubangi very probably result from both severe iodine and selenium deficiency together with thiocyanate overload. PMID:8427202

  13. Follicular mucinosis - Case report*

    PubMed Central

    Passos, Paola C. Vieira da Rosa; Zuchi, Manuela Ferrasso; Fabre, Andréa Buosi; Martins, Luis Eduardo A. Machado

    2014-01-01

    Follicular mucinosis, also known as alopecia mucinosa, is a cutaneous mucinosis histologically characterized by accumulation of dermal type mucin in the pilosebaceous follicle and sebaceous glands. It presents in two forms, a primary or idiopathic form and a secondary form associated with various benign or malignant processes. Among the malignant processes, the main association is with mycosis fungoides. The frequent overlap of clinical, histopathological, immunohistochemical and molecular biology characteristics makes the correct classification of these conditions difficult, therefore a long follow-up of all cases is recommended. We report the case of an adolescent with disseminated lesions and discuss the difficulty of early identification of secondary follicular mucinosis associated with cutaneous lymphoma. PMID:24770517

  14. Follicular thyroid carcinoma.

    PubMed

    Haigh, Philip I

    2002-08-01

    Follicular carcinomas are rare thyroid malignancies that are difficult to diagnose preoperatively. Fine needle aspiration is an excellent diagnostic tool and should be the initial step in managing the solitary thyroid nodule. Follicular carcinoma cannot be diagnosed with certainty by cytologic features alone; the diagnosis rests on the histologic findings of blood vessel or tumor capsule invasion. Surgical resection is the primary option for treatment. The extent of thyroidectomy for optimal survival outcome has not been determined scientifically. The outcome is excellent in minimally invasive follicular carcinoma with lobectomy and isthmusectomy; it is difficult to argue that total thyroidectomy is necessary. In a low risk prognostic group, for tumors other than minimally invasive carcinoma, lobectomy and isthmusectomy or total thyroidectomy can be justified. However, if total thyroidectomy can be done safely with a minimum of complications, then it has definite advantages for staging, postoperative surveillance, treatment, and possibly a lower recurrence rate and better survival rate. For all patients at high risk of recurrence, total thyroidectomy is preferred. PMID:12074771

  15. Endocrine and paracrine control of follicular development and ovulation rate in farm species.

    PubMed

    Hunter, M G; Robinson, R S; Mann, G E; Webb, R

    2004-07-01

    Productivity in farm species is controlled by many factors, including ovulation rate. In cattle, single ovulations occur most frequently and in sheep (and goats) the number of ova released can range from one to many depending upon the breed, whilst the pig is polyovular. The processes of recruitment and selection determine the number of ovulatory follicles in all these species with FSH and subsequently LH playing major roles. GnRH-agonist models in which endogenous gonadotrophin secretion is suppressed and exogenous LH and/or FSH are administered at specific concentrations in defined patterns, are useful in all three species for elucidating the precise roles of specific hormones in stimulating follicular development. Differences in the hypothalamic-pituitary-ovarian feedback response lead to the differences in the number of ovulatory follicles, as does the pool of antral follicles from which the ovulatory ones are selected. Precocious development of follicles is also associated with more ovulations, as is the case with the Booroola due to the single gene acting through bone morphogenetic proteins (BMPs). It is well established that ovulation rate can also be influenced by exogenous hormone administration and by environmental factors such as nutrition. It has become apparent that these nuritional effects are mediated by a direct action at the level of the ovary, involving insulin, insulin-like growth factors (IGF) I and II and their binding proteins among other factors. These factors can also affect the quality of the oocyte and consequently embryo development and survival. Recently, the regulation of follicular angiogenesis has been shown to be important for the development of ovulatory follicles, particularly vascular endothelial growth factor (VEGF) which is produced primarily by the granulosa cells within the ovary and can be stimulated by gonadotrophins. Administration of VEGF has been shown to stimulate pre-antral follicular growth and increase the number of

  16. Effect of estradiol-17β on follicle-stimulating hormone secretion and egg-laying performance of Japanese quail.

    PubMed

    Çiftci, H B

    2012-12-01

    The aim of this study was to measure the effect of estradiol-17β (E2) injection on follicle-stimulating hormone (FSH) secretion and egg-laying performance of Japanese quail. Female Japanese quail were housed in cages and fed ad libitum. After a 7-day adaptation period, the birds were randomly assigned to three groups, that is, one control group and two test groups. The birds were weighed, before every injection. The control group was subcutaneously injected with 0.2 ml sesame oil-ethanol mixture, whereas test groups were injected, twice in a week, with 0.2 ml sesame oil-ethanol mixture containing 0.1 or 0.2 mg E2 along the study. One day after the first injection, egg number, egg weight, eggshell strength and food conception were daily recorded. On the last day of the experiment, the birds were injected and 3 h later seven birds from each group were randomly selected for bleeding. Blood samples (2 ml/bird) were collected from the jugular vein for the measurements of serum concentrations of E2, FSH, calcium (Ca) and phosphorus (P). E2 injection did not cause any significant changes in serum FSH concentrations, daily egg laid/bird, food conception/bird, serum concentrations of the Ca and the P. Egg weight was significantly increased in the 0.1 mg E2-injected group as compared with the control and 0.2 mg E2-injected groups. Eggshell strength in the 0.2 mg E2-injected group was significantly high as compared with the control, whereas the difference between the 0.1 mg E2- and 0.2 mg E2-injected groups was not statistically important. These results show that serum FSH concentration was not increased even when slightly suppressed by subcutaneous injection of 0.1 or 0.2 mg E2. Different doses of E2 have different functions. The increase in BWs in the 0.1 mg E2-injected group was a result of the dose effect, which probably increased growth hormone secretion from the pituitary or IGF-1 synthesis from the liver or both. The dose, 0.2 mg E2, was ineffective in increasing the

  17. Profiling follicle stimulating hormone-induced gene expression changes in normal and malignant human ovarian surface epithelial cells.

    PubMed

    Ho, Shuk-Mei; Lau, Kin-Mang; Mok, Samuel Chi-Ho; Syed, Viqar

    2003-07-01

    Epidemiological data have implicated the pituitary gonadotropin follicle stimulating hormone (FSH) as both a risk factor for and a protective agent against epithelial ovarian cancer. Yet, little is known about how this hormone could play such opposing roles in ovarian carcinogenesis. Complementary DNA microarrays containing 2400 named genes were used to examine FSH-induced gene expression changes in ovarian cancer (OC) and immortalized normal human ovarian surface epithelial (HOSE) cell lines. Two-way t-statistics analyses of array data identified two distinct sets of FSH-regulated genes in HOSE and in established OC cell lines established from patients (OVCA cell lines). Among the HOSE cell lines, FSH increased expression of 57% of the 312 genes and downregulated 43%. In contrast, FSH diminished expression of 92% of the 177 genes in the OVCA cell lines. All but 18 of the genes affected by FSH in HOSE cell lines were different from those altered in OVCA cell lines. Among the 18 overlapping genes, nine genes exhibited the same direction of change following FSH challenge, while the other nine showed discordance in response between HOSE and OVCA cell lines. The FSH-induced differential expression of seven out of nine genes was confirmed by real-time RT-PCR. Gene-specific antisense oligonuleotides (ODNs) were used to inhibit the expression of genes encoding GTPase activating protein (rap1GAP), neogenin, and restin in HOSE and OVCA cells. Antisense ODNs to neogenin and restin, but not an antisense ODN to rap1GAP, were effective in inhibiting OVCA cell growth, diminishing proliferating cell nuclear antigen expression, and increasing caspase 3 activities. Furthermore, the ODN to rap1GAP was further shown to be ineffective in altering migration properties of OVCA cell lines. HOSE cell proliferation was not affected by treatment with any of the antisense ODNs. In summary, gene profiling data reveal for the first time that FSH may exert different biological actions on OVCA

  18. Assignment of the gene for the. beta. subunit of thyroid-stimulating hormone to the short arm of human chromosome 1

    SciTech Connect

    Dracopoli, N.C.; Rettig, W.J.; Whitfield, G.K.; Darlington, G.J.; Spengler, B.A.; Biedler, J.L.; Old, L.J.; Kourides, I.A.

    1986-03-01

    The chromosomal locations of the genes for the ..beta.. subunit of human thyroid-stimulating hormone (TSH) and the glycoprotein hormone ..cap alpha.. subunit have been determined by restriction enzyme analysis of DNA extracted from rodent-human somatic cell hybrids. Human chorionic gonadotropin (CG) ..cap alpha..-subunit cDNA and a cloned 0.9-kilobase (kb) fragment of the human TSH ..beta..-subunit gene were used as hybridization probes in the analysis of Southern blots of DNA extracted from rodent-human hybrid clones. Analysis of the segregation of 5- and 10-kb EcoRI fragments hybridizing to CG ..cap alpha..-subunit cDNA confirmed the previous assignment of this gene to chromosome 6. Analysis of the patterns of segregation of a 2.3-kb EcoRI fragment containing human TSH ..beta..-subunit sequences permitted the assignment of the TSH ..beta..-subunit gene to human chromosome 1. The subregional assignment of TSH ..beta.. subunit to chromosome 1p22 was made possible by the additional analysis of a set of hybrids containing partially overlapping segments of this chromosome. Human TSH ..beta.. subunit is not syntenic with genes encoding the ..beta.. subunits of CG, luteinizing hormone, or follicle-stimulating hormone and is assigned to a conserved linkage group that also contains the structural genes for the ..beta.. subunit of nerve growth factor (NGFB) and the proto-oncogene N-ras (NRAS).

  19. In vitro fertilization and development of porcine oocytes matured in follicular fluid.

    PubMed

    Agung, Budiyanto; Otoi, Takeshige; Fuchimoto, Dai-ichiro; Senbon, Shoichiro; Onishi, Akira; Nagai, Takashi

    2013-01-01

    This study was conducted to assess the fertilization and development of porcine oocytes matured in a solo follicular fluid (pFF) using different in vitro culture systems and insemination periods. Cumulus-oocyte complexes (COCs), follicular cells (FCs), and pFF were collected from the follicles of ovaries. The pFF was used as a maturation medium (MpFF) after supplementation with follicle stimulating hormone (FSH) and antibiotics. The COCs were matured in a 15 ml test tube containing 3.5 ml of MpFF with FCs (5.2 × 10(6) cells/ml; rotating culture system) or 2 ml of MpFF without FCs in a 35-mm petri dish (static culture system) for 44 to 48 h. After maturation culture, oocytes were co-incubated with frozen-thawed spermatozoa for 5 h and then cultured for 7 days. The total mean rates of sperm penetration, normal fertilization, male pronucleus (MPN) formation, cleavage, and development to the blastocyst stage of oocytes after insemination were significantly higher (P<0.01) in the rotating culture system than in the static culture system. In conclusion, compared with the static culture system, the rotating culture system is adequate for the production of developmentally competent porcine oocytes when MpFF is used as a maturation medium. PMID:23428620

  20. Regulation of the phosphoinositide pathway in cultured Sertoli cells from immature rats: effects of follicle-stimulating hormone and fluoride

    SciTech Connect

    Quirk, S.M.; Reichert, L.E. Jr.

    1988-07-01

    Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-(2-3H) inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total (3H)inositol phosphates ((3H)inositol mono-, di-, and triphosphates (IP, IP2, and IP3)) in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. Addition of testosterone and the combination of testosterone plus retinoic acid, agents that have been shown to potentiate effects of FSH in other systems, did not affect accumulation of inositol phosphates in response to FSH. In contrast to the lack of effect on accumulation of inositol phosphates, FSH stimulated 4- to 11-fold increases in estradiol secretion over 24 h of culture, indicating that Sertoli cells were viable and responsive to FSH. AIF4- has been shown to activate G-proteins involved in regulation of adenylate cyclase activity. In the present study, AIF4- induced 4- to 5-fold increases in IP, IP2, and IP3 in experiments wherein FSH had no effect. Pretreatment of Sertoli cells with pertussis toxin (100 and 1000 ng/ml) for 24 h inhibited fluoride-induced generation of IP, IP2, and IP3 by 24-51%. Similar treatment with cholera toxin had no effect on basal or fluoride-induced generation of IP2 or IP3, but increased fluoride-induced generation of IP by 20-34%.

  1. Histamine released from epidermal keratinocytes plays a role in α-melanocyte-stimulating hormone-induced itching in mice.

    PubMed

    Shimizu, Kyoko; Andoh, Tsugunobu; Yoshihisa, Yoko; Shimizu, Tadamichi

    2015-11-01

    Sunburn, wound repair, and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching. Proopiomelanocortin-derived α-melanocyte-stimulating hormone (α-MSH) is produced in response to external stimuli, such as UV irradiation, and is involved in cutaneous pigmentation. However, it is unclear whether α-MSH is also involved in the itching. We therefore investigated whether α-MSH elicited itch-related responses in mice. We found that an intradermal injection of α-MSH induced hind-paw scratching, an itch-related response, in mice. The α-MSH-induced scratching was inhibited by the μ-opioid receptor antagonist naltrexone and the H1 histamine receptor antagonist terfenadine. In mast cell-deficient mice, α-MSH also elicited scratching, which was inhibited by terfenadine. The immunoreactivity for l-histidine decarboxylase, a key enzyme required for the production of histamine, histamine, and the melanocortin 1 and 5 receptors were shown in not only mast cells but also keratinocytes in murine skin. In addition to the expression of l-histidine decarboxylase and melanocortin 1 and 5 receptors, the mouse keratinocyte cell lines (Pam212) also showed immunoreactivity for l-histidine decarboxylase, histamine, and melanocortin 1 and 5 receptors. The application of α-MSH induced the release of histamine from Pam212 cells. These findings indicate that α-MSH may play an important role in the itching associated with pigmented cutaneous lesions and that the histamine released from keratinocytes is involved in this α-MSH-induced itching. PMID:26358220

  2. Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis

    PubMed Central

    Xiong, Haibo; Wu, Mingxing; Yi, Hong; Wang, Xiuqing; Wang, Qian; Nadirshina, Sophia; Zhou, Xiyuan; Liu, Xueqin

    2016-01-01

    Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I2 = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I2 = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO. PMID:27456991

  3. A domestication related mutation in the thyroid stimulating hormone receptor gene (TSHR) modulates photoperiodic response and reproduction in chickens.

    PubMed

    Karlsson, Anna-Carin; Fallahshahroudi, Amir; Johnsen, Hanna; Hagenblad, Jenny; Wright, Dominic; Andersson, Leif; Jensen, Per

    2016-03-01

    The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a "domestication locus" in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects of a mutation in the gene on several domestication related traits, indicate that the gene has been important for chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We used birds from an advanced intercross line between ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects of the mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wild type allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling for background variation in the rest of the genome. TSHR gene expression in brain was significantly lower in both d/d females and males and d/d females showed a faster onset of egg laying at sexual maturity than w/w. Furthermore, d/d males showed a reduced testicular size response to decreased day length, and lower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under natural short day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3 expression compared to Red Junglefowl females kept under similar conditions. Our study indicates that the TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction, a typical domestication feature, and may therefore have been important for chicken domestication. PMID:26873630

  4. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    SciTech Connect

    Miao, Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  5. Follicle-stimulating hormone-induced rescue of cumulus cell apoptosis and enhanced development ability of buffalo oocytes.

    PubMed

    Jain, A; Jain, T; Kumar, P; Kumar, M; De, S; Gohain, M; Kumar, R; Datta, T K

    2016-04-01

    The effect of follicle-stimulating hormone (FSH) on apoptotic status of cumulus cells, expression of proapoptotic and antiapoptotic genes, and development rate of in vitro fertilization-produced buffalo embryos were investigated. FSH supplementation in in vitro maturation-medium resulted in a dose-dependent reduction in the expression of proapoptotic genes namely, BCL2-associated X protein (BAX), cytochrome c, and caspase-3 and increase in the expression of antiapoptotic genes such as B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) in cumulus cells of mature oocyte. Cumulus expansion, oocyte maturation, cleavage, and blastocyst development rates were significantly higher (P < 0.05) in 5 and 10-μg/mL FSH-supplemented groups as compared with control. Significant increase in the expression of FSH receptor messenger RNA was also found with 5 and 10-μg/mL FSH (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay confirmed that the population of apoptotic cumulus cells of matured oocytes was reduced in the FSH-treated groups as compared with control (P < 0.05). In conclusion, our data suggest that FSH may attenuate apoptosis in cumulus cells via mitochondria-dependent apoptotic pathway by increasing XIAP expression, resulting in a more favorable ratio of BCL2/BAX expression and decreasing the cytochrome c and caspase-3 expression, eventually contributing to developmental competence of oocytes. The information generated will help in improving the in vitro embryo production program in buffalo. PMID:26774556

  6. Impacts of incorporation of follicle stimulating hormone into an estrous synchronization protocol for timed artificial insemination of crossbred beef cattle.

    PubMed

    Gentry, G T; Walker, R S; Gentry, L R

    2016-05-01

    One-hundred-eighty crossbred beef cows and 66 crossbred beef heifers across three locations were stratified by body weight (BW), body condition score (BCS), and age (within location) to evaluate administration of follicle stimulating hormone (FSH) on Day 2 using a modified 7-day CO-Synch plus CIDR(®) protocol (Day 0=CIDR insertion) with timed-artificial insemination (TAI) at 72h (cows) or 54h (heifers) following CIDR removal. Estrous response following CIDR removal was determined using an Estrotect patch and TAI and final pregnancy rates were determined by transrectal ultrasonography 42-45days following TAI and ≥45days following removal of clean-up bulls. Estrous response rate, TAI and final pregnancy rates for cows were not affected (P≥0.65) by treatment. Cows that exhibited estrus had greater (P<0.01) TAI pregnancy rate (66%) than cows not exhibiting estrus (38%). There was an estrous response by postpartum length interaction (P=0.02) where cows exhibiting estrus and ≥55days postpartum had greater TAI pregnancy rates (75%) compared to cows not exhibiting estrus and <55days postpartum (39%) or ≥55days postpartum (28%). For heifers, timed AI (P=0.46) and final pregnancy rates (P=0.45) were similar across treatments and estrous response had no effect (P=0.30) on TAI pregnancy rates. In conclusion, the addition of FSH to the CO-Synch plus CIDR estrous synchronization protocol did not increase TAI pregnancy rates in beef cows or heifers. However, a positive estrous response to the synchronization protocol was associated with increased TAI pregnancy rates in cows. PMID:26968244

  7. How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

    PubMed Central

    Pokrovska, Tzveta; Jones, Jeremy; Shaikh, M Guftar; Smith, Sarah; Donaldson, Malcolm D C

    2016-01-01

    Objectives To determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of <10 pmol/L is unlikely, so that treatment with levo-thyroxine (L-T4) might be deferred until venous thyroid function tests (TFTs) become available. Subjects and methods All infants referred in Scotland since 1979 with capillary TSH elevation were studied, with particular focus on infants screened using the AutoDELFIA assay between 2002 and 2013. Results Of the 321 infants referred with capillary TSH elevation using AutoDELFIA, 35 were excluded (fT4/TSH unavailable (12), venous sample either preceding or >10 days after capillary sampling (13, 10)), leaving 286 eligible for analysis (208 definite/probable hypothyroidism, 61 transient TSH elevation, 17 of uncertain thyroid status). Capillary TSH and venous T4 were strongly correlated (Spearman's rank correlation coefficient −0.707355). The optimal capillary TSH threshold for predicting a venous fT4 of <10 pmol/L was found to be >40 mU/L (90.3% sensitivity and 65.9% specificity compared with 90.25% and 59.1% for >35 mU/L and 88.3% and 68.2% for >45 mU/L). 93 infants (32.5%) had capillary TSH ≤40 mU/L at referral of whom 15 (9.7%) had venous fT4 <10 pmol/L, comprising seven with true congenital hypothyroidism, five with transient TSH elevation and three with uncertain status, two of whom died. Conclusion For infants in whom capillary TSH is ≤40 mU/L, it is reasonable to defer L-T4 treatment until venous TFT results are known provided that the latter become available quickly. PMID:26966265

  8. Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis.

    PubMed

    Xiong, Haibo; Wu, Mingxing; Yi, Hong; Wang, Xiuqing; Wang, Qian; Nadirshina, Sophia; Zhou, Xiyuan; Liu, Xueqin

    2016-01-01

    Graves' disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61-0.73, P = 0.000, I(2) = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53-1.83, P = 0.000, I(2) = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO. PMID:27456991

  9. Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism.

    PubMed

    Watson, S G; Radford, A D; Kipar, A; Ibarrola, P; Blackwood, L

    2005-09-01

    Hyperthyroidism is the most common endocrinopathy in cats, and is both clinically and histopathologically very similar to human toxic nodular goitre (TNG). Molecular studies on human TNG have revealed the presence of mis-sense mutations in the thyroid-stimulating hormone receptor (TSHR) gene, most frequently in exon 10. Our hypothesis was that similar mutations exist in hyperthyroid cats. Genomic DNA was extracted from 134 hyperplastic/adenomatous nodules (from 50 hyperthyroid cats), and analysed for the presence of mutations in exon 10 of the TSHR gene. 11 different mutations were detected, one silent and 10 mis-sense, of which nine were somatic mutations. 28 of the 50 cats (67/134 nodules) had at least one mis-sense mutation. The mis-sense mutations were Met-452-->Thr in 17 cats (35 nodules), Ser-504-->Arg (two different mutational forms) in two cats (two nodules), Val-508-->Arg in one cat (three nodules), Arg-530-->Gln in one cat (two nodules), Val-557-->Leu in 13 cats (36 nodules), Thr-631-->Ala or Thr-631-->Phe (each mutation seen in one nodule of one cat), Asp-632-->Tyr in six cats (10 nodules) and Asp-632-->His in one cat (one nodule). Five of these mutations have been associated previously with human hyperthyroidism. Of the 41 cats for which more than one nodule was available, 14 had nodules with different mutations. The identification of a potential genetic basis for feline hyperthyroidism is novel, increases our understanding of the pathogenesis of this significant feline disease, and confirms its similarity to TNG. PMID:16135672

  10. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... medicines you take. These include: Birth control pills Hormone therapy Testosterone DHEA (a supplement) If you are ...

  11. Loss of GATA-6 and GATA-4 in Granulosa Cells Blocks Folliculogenesis, Ovulation, and Follicle Stimulating Hormone Receptor Expression Leading to Female Infertility

    PubMed Central

    Bennett, Jill; Wu, Yan-Guang; Gossen, Jan; Zhou, Ping

    2012-01-01

    Single GATA-6 (G6gcko), GATA-4 (G4gcko), and double GATA-4/6 (G4/6gcko) granulosa cell-specific knockout mice were generated to further investigate the role of GATA transcription factors in ovarian function in vivo. No reproductive defects were found in G6gcko animals. G4gcko animals were subfertile as indicated by the reduced number of pups per litter and the release of significantly fewer oocytes at ovulation. In marked contrast, G4/6gcko females fail to ovulate and are infertile. Furthermore, G4/6gcko females had irregular estrous cycles, which correlate with the abnormal ovarian histology found in unstimulated adult G4/6gcko females showing lack of follicular development and increased follicular atresia. Moreover, treatment with exogenous gonadotropins did not rescue folliculogenesis or ovulation in double-knockout G4/6gcko mice. In addition, ovary weight and estradiol levels were significantly reduced in G4gcko and G4/6gcko animals when compared with control and G6gcko mice. Aromatase, P450scc, and LH receptor expression was significantly lower in G4gcko and G4/6gcko mice when compared with control animals. Most prominently, FSH receptor (FSHR) protein was undetectable in granulosa cells of G4gcko and G4/6gcko. Accordingly, gel shift and reporter assays revealed that GATA-4 binds and stimulates the activity of the FSHR promoter. These results demonstrate that GATA-4 and GATA-6 are needed for normal ovarian function. Our data are consistent with a role for GATA-4 in the regulation of the FSHR gene and provide a possible molecular mechanism to explain the fertility defects observed in animals with deficient GATA expression in the ovary. PMID:22434075

  12. Treatment with recombinant equine follicle stimulating hormone (reFSH) followed by recombinant equine luteinizing hormone (reLH) increases embryo recovery in superovulated mares.

    PubMed

    Meyers-Brown, G; Bidstrup, L A; Famula, T R; Colgin, M; Roser, J F

    2011-10-01

    The dynamics of ovarian follicular development depend on a timely interaction of gonadotropins and gonadal feedback in the mare. The development and efficacy of genetically cloned recombinant equine gonadotropins (reFSH and reLH) increase follicular activity and induce ovulation, respectively, but an optimum embryo recovery regimen in superovulated mares has not been established. The objective of this study was to determine if treatment with reFSH followed by reLH would increase the embryo per ovulation ratio and the number of embryos recovered after superovulation in mares. Sixteen estrous cycling mares of light horse breeds (4-12 years) were randomly assigned to one of two groups: Group 1; reFSH (0.65mg)/PBS (n=8) and Group 2; reFSH (0.65mg)/reLH (1.5mg) (n=8). On the day of a 22-25mm follicle post-ovulation mares were injected IV twice daily with reFSH for 3 days (PGF(2α) given IM on the second day of treatment) and once per day thereafter until a follicle or cohort of follicles reached 29mm after which either PBS or reLH was added and both groups injected IV twice daily until the presence of a 32mm follicles, when reFSH was discontinued. Thereafter, mares were injected three times daily IV with only PBS or reLH until a majority of follicles reached 35-38mm when treatment was discontinued. Mares were given hCG IV (2500IU) to induce ovulation and bred. Embryo recovery was performed on day 8 day post-treatment ovulation. Daily jugular blood samples were collected from the time of first ovulation until 8 days post-treatment ovulation. Blood samples were analyzed for LH, FSH, estradiol, progesterone and inhibin by validated RIA. Duration of treatment to a ≥35mm follicle(s) and number of ovulatory size follicles were similar between reFSH/reLH and reFSH/PBS treated mares. The number of ovulations was greater (P<0.01) in the reFSH/reLH group, while the number of anovulatory follicles was less (P<0.05) compared to the reFSH/PBS group. Number of total embryos

  13. Rapid breakdown of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in rat hepatocytes stimulated by vasopressin and other Ca2+-mobilizing hormones.

    PubMed Central

    Creba, J A; Downes, C P; Hawkins, P T; Brewster, G; Michell, R H; Kirk, C J

    1983-01-01

    Rat hepatocytes rapidly incorporate [32P]Pi into phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; their monoester phosphate groups approach isotopic equilibrium with the cellular precursor pools within 1 h. Upon stimulation of these prelabelled cells with Ca2+-mobilizing stimuli (V1-vasopressin, angiotensin, alpha 1-adrenergic, ATP) there is a rapid fall in the labelling of PtdIns4P and PtdIns(4,5)P2. Pharmacological studies suggest that each of the four stimuli acts at a different population of receptors. Insulin, glucagon and prolactin do not provoke disappearance of labelled PtdIns4P and PtdIns(4,5)P2. The labelling of PtdIns4P and PtdIns(4,5)P2 in cells stimulated with vasopressin or angiotensin initially declines at a rate of 0.5-1.0% per s, reaches a minimum after 1-2 min and then returns towards the initial value. The dose-response curves for the vasopressin- and angiotensin-stimulated responses lie close to the respective receptor occupation curves, rather than at the lower hormone concentrations needed to evoke activation of glycogen phosphorylase. Disappearance of labelled PtdIns4P and PtdIns(4,5)P2 is not observed when cells are incubated with the ionophore A23187. The hormone-stimulated polyphosphoinositide disappearance is reduced, but not abolished, in Ca2+-depleted cells. These hormonal effects are not modified by 8-bromo cyclic GMP, cycloheximide or delta-hexachlorocyclohexane. The absolute rate of polyphosphoinositide breakdown in stimulated cells is similar to the rate previously reported for the disappearance of phosphatidylinositol [Kirk, Michell & Hems (1981) Biochem. J. 194, 155-165]. It seems likely that these changes in polyphosphoinositide labelling are caused by hormonal activation of the breakdown of PtdIns(4,5)P2 (and may be also PtdIns4P) by the action of a polyphosphoinositide phosphodiesterase. We therefore suggest that the initial response to hormones is breakdown of PtdIns(4,5)P2

  14. Transmission Electron Microscopy (TEM) Observations of Female Oocytes From Nilaparvata lugens (Hemiptera: Delphacidae): Antibiotic Jinggangmycin (JGM)-Induced Stimulation of Reproduction and Associated Changes in Hormone Levels.

    PubMed

    Xu, Bing; You, Lin-Lin; Wu, You; Ding, Jun; Ge, Lin-Quan; Wu, Jin-Cai

    2016-08-01

    Previous studies have demonstrated that the agricultural antibiotic jinggangmycin (JGM) stimulates reproduction in the brown planthopper Nilaparvata lugens Stål and that the stimulation of brown planthopper reproduction induced by JGM is regulated by the fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) genes. However, a key issue in the stimulation of reproduction induced by pesticides involves the growth and development of oocytes. Therefore, the present study investigated oocyte changes via transmission electron microscopy (TEM) and changes in hormone levels (juvenile hormones (JH) and 20-hydroxyecdysone (20 E)) in JGM-treated females. TEM observations showed that the size of the lipid droplets in the oocytes of JGM-treated females, compared with those in the oocytes of the control females, significantly reduced by 32.6 and 29.8% at 1 and 2 d after emergence (1 and 2 DAE), respectively. In addition, the JH levels of JGM-treated females at 1 and 2 DAE were increased by 49.7 and 45.7%, respectively, whereas 20 E levels decreased by 36.0 and 30.0%, respectively. We conclude that JGM treatments lead to substantial changes in lipid metabolism, which are directly and indirectly related to stimulation of reproduction of brown planthopper together with our previous findings. PMID:27247297

  15. Transmission Electron Microscopy (TEM) Observations of Female Oocytes From Nilaparvata lugens (Hemiptera: Delphacidae): Antibiotic Jinggangmycin (JGM)-Induced Stimulation of Reproduction and Associated Changes in Hormone Levels

    PubMed Central

    You, Lin-Lin; Wu, You; Ding, Jun; Ge, Lin-Quan; Wu, Jin-Cai

    2016-01-01

    Previous studies have demonstrated that the agricultural antibiotic jinggangmycin (JGM) stimulates reproduction in the brown planthopper Nilaparvata lugens Stål and that the stimulation of brown planthopper reproduction induced by JGM is regulated by the fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) genes. However, a key issue in the stimulation of reproduction induced by pesticides involves the growth and development of oocytes. Therefore, the present study investigated oocyte changes via transmission electron microscopy (TEM) and changes in hormone levels (juvenile hormones (JH) and 20-hydroxyecdysone (20 E)) in JGM-treated females. TEM observations showed that the size of the lipid droplets in the oocytes of JGM-treated females, compared with those in the oocytes of the control females, significantly reduced by 32.6 and 29.8% at 1 and 2 d after emergence (1 and 2 DAE), respectively. In addition, the JH levels of JGM-treated females at 1 and 2 DAE were increased by 49.7 and 45.7%, respectively, whereas 20 E levels decreased by 36.0 and 30.0%, respectively. We conclude that JGM treatments lead to substantial changes in lipid metabolism, which are directly and indirectly related to stimulation of reproduction of brown planthopper together with our previous findings. PMID:27247297

  16. Growth hormone stimulation test

    MedlinePlus

    Arginine test; Arginine-GHRH test ... of re-inserting the needle each time. The test takes between 2 to 5 hours. The procedure ... eat for 10 to 12 hours before the test. Eating food can change the test results. Some ...

  17. Fine Structures of the Oocyte in Relation to Serum, Follicular Fluid Steroid Hormones and IGF-I in the Ovulatory-Sized Follicles in One-Humped Camel (Camelus dromedarius)

    PubMed Central

    Kafi, Mojtaba; Mesbah, Seyed Fakhroddin; Davoodian, Najmeh; Kadivar, Ali

    2014-01-01

    Background The following study was carried out to determine the ultrastructural features of the oocyte of the ovulatory-sized follicles in relation to concentrations of steroids and IGF-I in the Follicular Fluid (FF) and serum in the dromedary camel. Methods Camel follicles with a clear and healthy appearance were categorized into three classes: follicles 10 to 13.9, 14-17.9 and 18-30 mm diameter. The FF and serum samples were assayed for estradiol-17β, progesterone and IGF-I. Recovered Cumulus-Oocyte Complexes (COCs) were prepared for transmission electron microscopy. Results The mean (±SD) FF concentrations of progesterone and IGF-I was significantly (p < 0.05) higher in follicles 18 to 30 mm diameter compared to other groups of follicles. There was no difference in the mean (±SD) serum estradiol-17β, progesterone and IGF-I concentrations between camels with different ovulatory-sized follicles (p > 0.05). Oocytes from follicles 18 to 30 mm diameter (group 3) showed more advanced signs of maturation including the disappearance of the nuclear envelope, increased number of microvilli in erect position, the increase in number and size of vesicles and more even distribution of the mitochondria throughout the ooplasm. Conclusion The final stages of oocyte maturation in dromedary camel is associated with increasing progesterone and IGF-I concentrations and constant high estradiol concentration in the follicular fluid which are paralleled with well-defined ultrastructural changes in oocytes. PMID:24551433

  18. ACTH (cosyntropin) stimulation test

    MedlinePlus

    ... The ACTH stimulation test measures how well the adrenal glands respond to adrenocorticotropic hormone ( ACTH ). ACTH is a ... produced in the pituitary gland that stimulates the adrenal glands to release a hormone called cortisol. How the ...

  19. Follicular Helper T Cells.

    PubMed

    Vinuesa, Carola G; Linterman, Michelle A; Yu, Di; MacLennan, Ian C M

    2016-05-20

    Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination. PMID:26907215

  20. The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans.

    PubMed

    Berkenstam, Anders; Kristensen, Jens; Mellström, Karin; Carlsson, Bo; Malm, Johan; Rehnmark, Stefan; Garg, Neeraj; Andersson, Carl Magnus; Rudling, Mats; Sjöberg, Folke; Angelin, Bo; Baxter, John D

    2008-01-15

    Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis. PMID:18160532

  1. The Effect of a Mutation in the Thyroid Stimulating Hormone Receptor (TSHR) on Development, Behaviour and TH Levels in Domesticated Chickens

    PubMed Central

    Karlsson, Anna-Carin; Svemer, Frida; Eriksson, Jonas; Darras, Veerle M.; Andersson, Leif; Jensen, Per

    2015-01-01

    The thyroid stimulating hormone receptor (TSHR) has been suggested to be a “domestication locus” in the chicken, due to a strong selective sweep over the gene found in domesticated chickens, differentiating them from their wild ancestor the Red Junglefowl (RJF). We investigated the effect of the mutation on development (incubation time), behaviour and thyroid hormone levels in intercross chickens homozygous for the mutation (d/d), wild type homozygotes (w/w) or heterozygotes (d/w). This allowed an assessment of the effect of genotype at this locus against a random mix of RJF and WL genotypes throughout the rest of the genome, controlling for family effects. The d/d genotype showed a longer incubation time, less fearful behaviours, lower number of aggressive behaviours and decreased levels of the thyroid hormone T4, in comparison to the w/w genotype. The difference between TSHR genotypes (d/d vs. w/w) in these respects mirrors the differences in development and behaviour between pure domesticated White Leghorns and pure RJF chickens. Higher individual T3 and T4 levels were associated with more aggression. Our study indicates that the TSHR mutation affects typical domestication traits, possibly through modifying plasma levels of thyroid hormones, and may therefore have been important during the evolution of the domestic chicken. PMID:26053744

  2. The Effect of a Mutation in the Thyroid Stimulating Hormone Receptor (TSHR) on Development, Behaviour and TH Levels in Domesticated Chickens.

    PubMed

    Karlsson, Anna-Carin; Svemer, Frida; Eriksson, Jonas; Darras, Veerle M; Andersson, Leif; Jensen, Per

    2015-01-01

    The thyroid stimulating hormone receptor (TSHR) has been suggested to be a "domestication locus" in the chicken, due to a strong selective sweep over the gene found in domesticated chickens, differentiating them from their wild ancestor the Red Junglefowl (RJF). We investigated the effect of the mutation on development (incubation time), behaviour and thyroid hormone levels in intercross chickens homozygous for the mutation (d/d), wild type homozygotes (w/w) or heterozygotes (d/w). This allowed an assessment of the effect of genotype at this locus against a random mix of RJF and WL genotypes throughout the rest of the genome, controlling for family effects. The d/d genotype showed a longer incubation time, less fearful behaviours, lower number of aggressive behaviours and decreased levels of the thyroid hormone T4, in comparison to the w/w genotype. The difference between TSHR genotypes (d/d vs. w/w) in these respects mirrors the differences in development and behaviour between pure domesticated White Leghorns and pure RJF chickens. Higher individual T3 and T4 levels were associated with more aggression. Our study indicates that the TSHR mutation affects typical domestication traits, possibly through modifying plasma levels of thyroid hormones, and may therefore have been important during the evolution of the domestic chicken. PMID:26053744

  3. Immunocytochemical Localization and Biochemical Characterization of alpha-Melanocyte-Stimulating Hormon in the Brain of the Rainbow Trout, Salmo gairdneri.

    PubMed

    Vallarino, M; Delbende, C; Ottonello, I; Tranchand-Bunel, D; Jegou, S; Vaudry, H

    1989-02-01

    Abstract The distribution of alpha-melanocyte-stimulating hormone (alpha-MSH)-like immunoreactivity in the central nervous system of the rainbow trout Salmo gairdneri was investigated by indirect immunofluorescence and peroxidase-antiperoxidase techniques, using a highly specific antiserum generated in rabbits against synthetic alpha-MSH. Immunoreactive perikarya were exclusively observed in the basal hypothalamus within the pars anterioris of the nucleus lateralis tuberis. In this region, a moderate number of small stained cell bodies were observed surrounding the dorsal wall of the anterior infundibular recess. These immunoreactive cells were organized in rostro-caudal rows extending over the whole portion of the nucleus. Positive fibres originating from these perikarya were visualized in the dorsal posterior lobe and the ventral hypothalamus. A dense tract of immunoreactive fibres projected ventrally through the pituitary stalk and terminated in the neurohypophysis. The concentrations of alpha-MSH in different regions of the brain were measured by means of a sensitive and specific radioimmunoassay. The dilution curves obtained with synthetic alpha-MSH and serial dilutions of diencephalon, mesencephalon, medulla oblongata, telencephalon or pituitary extracts were strictly parallel. The highest concentration of alpha-MSH in brain was found in the diencephalon (1.31 +/- 0.07 ng/mg protein). In contrast alpha-MSH was not detectable in cerebellar extracts. Reverse-phase high-performance liquid chromatography and radioimmunoassay were used to characterize alpha-MSH-like peptides in the trout brain and pituitary. Two major forms of immunoreactive alpha-MSH were resolved by high performance liquid chromatography in hypothalamic extracts; these peptides exhibited the same retention times as des-Na-acetyl alpha-MSH and its sulfoxide derivative, respectively. Additional peaks of alpha-MSH immunoreactive material were detected in pituitary extract. These latter peptides

  4. Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

    SciTech Connect

    Gallagher, Carolyn M.; Moonga, Baljit S.; Kovach, John S.

    2010-01-15

    Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal and perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH

  5. Human growth hormone (GH)-releasing factor stimulates and somatostatin inhibits the release of rat GH variants.

    PubMed

    Yokoya, S; Friesen, H G

    1986-11-01

    Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) was used for the analysis of proteins secreted by male rat pituitary cells in monolayer culture in the presence of 10 nM human GH-releasing factor (hGRF) or 30 nM somatostatin (SRIF) or in the absence of these factors. More than 300 medium proteins were reproducibly detected either by fluorographic autoradiography or by silver staining. Immunoreactivity of each protein was examined after 2D PAGE followed by Western blotting and immunostaining with affinity-purified antirat GH (rGH) antibody. While there was a cluster of immunoreactive spots in the GH dimer range (40,000-50,000 mol wt), at least 16 medium proteins of mol wt 22,000 or less were also stained. Among these 16 proteins the release of 15 was stimulated and the release of 14 was inhibited by hGRF and SRIF, respectively. On the other hand, there were 3 proteins of approximate mol wt 16,000 whose secretion was regulated in a coordinate manner as rGH by the hypothalamic factors but which did not cross-react with anti-rGH antibodies. The increase or decrease in the radioactivity of each protein spot obtained from media after pituitary cells were incubated with [35S]methionine and hypothalamic factors was analyzed statistically. A pulse-chase study suggested that at least 7 of the hormonally regulated proteins, including rGH, were synthesized very rapidly. Finally, the 2D PAGE analysis of cell-free translation products of messenger RNA derived from male rat anterior pituitaries revealed the presence of about 40 rGH-immunoreactive proteins which included pre-GH. These data suggest that there are multiple forms of rGH-variants or rGH-related proteins. The biological significance(s) of all the rGH immunoreactive proteins and of the GRF- and SRIF-regulated pituitary proteins remains unclear. It is evident that a number of these proteins are synthesized and released rapidly by pituitary cells in culture. Furthermore, the presence of multiple genes for

  6. Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression.

    PubMed

    Ibrahim, Sherif A; El-Ghonaimy, Eslam A; Hassan, Hebatallah; Mahana, Noha; Mahmoud, Mahmoud Abdelbaky; El-Mamlouk, Tahani; El-Shinawi, Mohamed; Mohamed, Mona M

    2016-09-01

    Hormonal-receptor positive (HRP) breast cancer patients with positive metastatic axillary lymph nodes are characterized by poor prognosis and increased mortality rate. The mechanisms by which cancer cells invade lymph nodes have not yet been fully explored. Several studies have shown that expression of IL-6 and the proteolytic enzyme cathepsin B (CTSB) was associated with breast cancer poor prognosis. In the present study, the effect of different concentrations of recombinant human IL-6 on the invasiveness capacity of HRP breast cancer cell line MCF-7 was tested using an in vitro invasion chamber assay. The impact of IL-6 on expression and activity of CTSB was also investigated. IL-6 treatment promoted the invasiveness potential of MCF-7 cells in a dose-dependent manner. Furthermore, MCF-7 cells displayed elevated CTSB expression and activity associated with loss of E-cadherin and upregulation of vimentin protein levels upon IL-6 stimulation. To validate these results in vivo, the level of expression of IL-6 and CTSB in the carcinoma tissues of HRP-breast cancer patients with positive and negative axillary metastatic lymph nodes (pLNs and nLNs) was assessed. Western blot and immunohistochemical staining data showed that expression of IL-6 and CTSB was higher in carcinoma tissues in HRP-breast cancer with pLNs than those with nLNs patients. ELISA results showed carcinoma tissues of HRP-breast cancer with pLNs exhibited significantly elevated IL-6 protein levels by approximately 2.8-fold compared with those with nLNs patients (P < 0.05). Interestingly, a significantly positive correlation between IL-6 and CTSB expression was detected in clinical samples of HRP-breast cancer patients with pLNs (r = 0.78, P < 0.01). Collectively, this study suggests that IL-6-induced CTSB may play a role in lymph node metastasis, and that may possess future therapeutic implications for HRP-breast cancer patients with pLNs. Further studies are necessary to fully identify IL-6/CTSB

  7. Tc-99m-labeled RGD-conjugated alpha-melanocyte stimulating hormone hybrid peptides with reduced renal uptake

    PubMed Central

    Yang, Jianquan; Hu, Chien-An

    2015-01-01

    The purpose of this study was to examine whether the replacement of the positively-charged Lys or Arg linker with a neutral linker could reduce the renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3–13 {(Arg11)CCMSH} through the neutral βAla or Ahx {aminohexanoic acid} linker (replacing the Lys or Arg linker) to generate novel RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH hybrid peptides. The receptor binding affinity and cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma cells. The melanoma targeting and imaging properties of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The replacement of the Lys or Arg linker with the βAla or Ahx linker retained nanomolar receptor binding affinities and remarkable cytotoxicity of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH. The receptor binding affinities of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH were 0.8 and 1.3 nM. Three-hour incubation with 0.1 µM of RGD-βAla-(Arg11)CCMSH and RGD-Ahx-(Arg11)CCMSH decreased the survival percentages of B16/F1 cells by 71 and 67% as compared to the untreated control cells five days post the treatment. The replacement of the Arg linker with the βAla or Ahx linker reduced the non-specific renal uptake of 99mTc-RGD-βAla-(Arg11)CCMSH and 99mTc-RGD-Ahx-(Arg11)CCMSH by 62% and 61% at 2 h post-injection. 99mTc-RGD-βAla-(Arg11)CCMSH displayed higher melanoma uptake than 99mTc-RGD-Ahx-(Arg11)CCMSH at 0.5, 2, 4 and 24 h post-injection. Enhanced tumor to kidney uptake ratio of 99mTc-RGD-βAla-(Arg11)CCMSH warranted the further evaluation of 188Re-labeled RGD-βAla-(Arg11)CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future. PMID:25557051

  8. Targeted Photothermal Ablation of Murine Melanomas with Melanocyte-Stimulating Hormone Analog-Conjugated Hollow Gold Nanospheres

    PubMed Central

    Lu, Wei; Xiong, Chiyi; Zhang, Guodong; Huang, Qian; Zhang, Rui; Zhang, Jin Z.; Li, Chun

    2009-01-01

    Purpose To develop melanoma-targeted hollow gold nanospheres (HAuNS) and evaluate their potential utility for selective photothermal ablation (PTA) in melanoma. Experimental Design A new class of photothermal coupling agents based on HAuNS was synthesized. HAuNS were stabilized with poly(ethylene-glycol) coating and attached with α-melanocyte-stimulating hormone analog, [Nle4,D-Phe7]α-MSH (NDP-MSH), which is a potent agonist of melanocortin type-1 receptor overexpressed in melanoma. The intracellular uptake of the NDP-MSH-conjugated PEGylated HAuNS (NDP-MSH-PEG-HAuNS) and the distribution of β-arrestin were examined in murine B16/F10 melanoma cells. The biodistribution of NDP-MSH-PEG-HAuNs was assessed at 4 h post intravenous injection in tumor-bearing nude mice. PTA effect of the nanoparticles was evaluated both histologically using excised tissue and functionally by [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Results NDP-MSH-PEG-HAuNS consist only of a thin gold wall with hollow interior (outer diameter, 43.5±2.3 nm; shell thickness, 3–4 nm), which display strong and tunable resonance absorption in near-infrared region (NIR, peak 808 nm). The nanoparticles were specifically taken up by melanoma cells, which initiated the recruitment of β-arrestins, the adapters to link the activated G-protein-coupled receptors to clathrin, indicating the involvement of receptor-mediated endocytosis. This resulted in enhanced extravasation of NDP-MSH-PEG-HAuNS from tumor blood vessels and their dispersion into tumor matrix compared with non-specific PEGylated HAuNS. Successful selective PTA of B16/F10 melanoma with targeted HAuNS was confirmed by histological and [18F]FDG-PET evaluation at 24 h post NIR laser irradiation at a low dose energy of 30 J/cm2. Conclusion NDP-MSH-PEG-HAuNS have the potentials to mediate targeted photothermal ablation of melanoma. PMID:19188158

  9. Microinjections of α-melanocyte stimulating hormone into the nucleus ambiguus of the rat elicit vagally mediated bradycardia

    PubMed Central

    Chitravanshi, Vineet C.; Bhatt, Suresh; Sapru, Hreday N.

    2009-01-01

    Neurons that immunostain for alpha-melanocyte stimulating hormone (α-MSH) have been identified in the nucleus ambiguus (nAmb). The presence of mRNA for melanocortin type 4 receptors (MC4Rs) has also been reported in this nucleus. On the basis of this information, it was hypothesized that activation of MC4Rs in the nAmb may play a role in the regulation of cardiac function. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (30 nl) of α-MSH (0.1, 0.2, 0.4, 0.8, and 1.2 mM) into the nAmb of anesthetized rats elicited decreases in heart rate (HR; 1.3 ± 0.6, 3 ± 1, 11 ± 2, 46.3 ± 3, and 43.3 ± 7 bpm, respectively) and no changes in mean arterial pressure (MAP). Maximum decreases in HR were elicited by 0.8 mM concentration of α-MSH. Bradycardic responses to α-MSH were similar in unanesthetized midcollicular decerebrate rats. Microinjections of artificial cerebrospinal fluid (30 nl) into the nAmb did not elicit a HR response. Bilateral vagotomy completely abolished α-MSH-induced bradycardia. The decreases in HR elicited by α-MSH (0.8 mM) were completely blocked by a selective MC4R antagonist. Direct application of α-MSH on the nAmb neurons increased their firing, which was blocked by prior applications of the MC4R antagonist. Microinjections of the MC4R antagonist into the nAmb did not alter reflex bradycardic responses elicited by intravenous infusions of phenylephrine, suggesting that MC4Rs did not play a role in mediating the parasympathetic component of baroreflex-induced bradycardia. These results indicated that α-MSH microinjections into the nAmb exert excitatory effects on parasympathetic preganglionic nAmb neurons via MC4Rs, leading to bradycardic responses. PMID:19297540

  10. The association between serum thyroid-stimulating hormone in its reference range and bone status in postmenopausal American women.

    PubMed

    Morris, Martha Savaria

    2007-04-01

    Evidence suggests that hyperthyroidism adversely affects bone, but the condition is rare and probably contributes little to postmenopausal osteoporosis. Subclinical hyperthyroidism, which can result from treatment with L-thyroxine, is more common, but its relationship to osteoporosis and fracture is uncertain. A recent study of healthy, postmenopausal Koreans with no history of thyroid disease reported associations between both below-normal and low-normal circulating thyroid-stimulating hormone (TSH) levels and osteoporosis. These findings raise the hypothesis that variation in thyroid function, or TSH itself, affects bone in normal women. In the present research, we used data collected in the third U.S. National Health and Nutrition Examination Survey to examine associations between TSH, as it varies over its reference range, and bone status in healthy, postmenopausal American women. In some analyses, we used osteoporosis and osteopenia defined according to World Health Organization guidelines as the outcome variable. In others, we used bone mineral density (BMD) as a continuum. After adjustment for age, race/ethnicity, body mass index, serum T(4), estrogen replacement therapy, smoking, and physical activity level, the odds ratios (95% CI) relating TSH between 0.39 and 1.8 mIU/L (the median of the reference range) versus TSH between 1.8 and 4.5 to osteoporosis and osteopenia were 3.4 (95% CI, 1.3-9.2) and 2.2 (1.2-3.8), respectively. Furthermore, BMD increased significantly as TSH increased over its reference range in both black and white women. After multivariate adjustment, least-square mean BMD for non-Hispanic white women in the bottom serum TSH quintile category was 0.79 g/cm(2) (95% CI, 0.76-0.82), as compared to 0.83 g/cm(2) (95% CI, 0.8-0.85) for those in the top quintile category. Least-square mean BMD (95% CI) for non-Hispanic black women in the bottom serum TSH quintile category was 0.85 g/cm(2) (95% CI, 0.81-0.89). For non-Hispanic black women in the

  11. The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation.

    PubMed

    Kol, Shahar; Homburg, Roy; Alsbjerg, Birgit; Humaidan, Peter

    2012-06-01

    Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-releasing hormone antagonist protocol should be the protocol of choice for the PCOS patient undergoing ovarian stimulation with gonadotropins for in vitro fertilization. If an excessive ovarian response is encountered, the clinician will always have two options: either to trigger final oocyte maturation with a bolus of GnRHa and supplement the luteal phase with a small bolus of human chorionic gonadotropin in addition to the standard luteal phase support and transfer in the fresh cycle or, alternatively, to trigger with GnRHa and perform a total freeze, resulting in a complete elimination of OHSS and high ongoing pregnancy rates in the subsequent frozen-thawed transfer cycles. PMID:22428986

  12. Dynamics of lipid droplet-associated proteins during hormonally stimulated lipolysis in engineered adipocytes: stabilization and lipid droplet binding of adipocyte differentiation-related protein/adipophilin.

    PubMed

    Gross, Danielle N; Miyoshi, Hideaki; Hosaka, Toshio; Zhang, Hui-Hong; Pino, Elizabeth C; Souza, Sandra; Obin, Martin; Greenberg, Andrew S; Pilch, Paul F

    2006-02-01

    In mature adipocytes, triglyceride is stored within lipid droplets, which are coated with the protein perilipin, which functions to regulate lipolysis by controlling lipase access to the droplet in a hormone-regulatable fashion. Adipocyte differentiation-related protein (ADRP) is a widely expressed lipid droplet binding protein that is coexpressed with perilipin in differentiating fat cells but is minimally present in fully differentiated cultured adipocytes. We find that fibroblasts ectopically expressing C/EBPalpha (NIH-C/EBPalpha cells) differentiate into mature adipocytes that simultaneously express perilipin and ADRP. In response to isoproterenol, perilipin is hyperphosphorylated, lipolysis is enhanced, and subsequently, ADRP expression increases coincident with it surrounding intracellular lipid droplets. In the absence of lipolytic stimulation, inhibition of proteasomal activity with MG-132 increased ADRP levels to those of cells treated with 10 mum isoproterenol, but ADRP does not surround the lipid droplet in the absence of lipolytic stimulation. We overexpressed a perilipin A construct in NIH-C/EBPalpha cells where the six serine residues known to be phosphorylated by protein kinase A were changed to alanine (Peri A Delta1-6). These cells show no increase in ADRP expression in response to isoproterenol. We propose that ADRP can replace perilipin on existing lipid droplets or those newly formed as a result of fatty acid reesterification, under dynamic conditions of hormonally stimulated lipolysis, thus preserving lipid droplet morphology/structure. PMID:16239256

  13. The meiotic response of cumulus cell-enclosed mouse oocytes to follicle-stimulating hormone in the presence of different macromolecules.

    PubMed

    Downs, S M; Dow, M P; Fagbohun, C F

    1991-06-01

    Experiments were carried out to determine the effect of different macromolecules on the follicle-stimulating hormone (FSH)-induced maturation of mouse oocytes in culture. Cumulus cell-enclosed oocytes (CEO) were isolated from gonadotropin-primed mice and maintained in meiotic arrest for 17-18 h with the cAMP analogue, dibutyryl cAMP (dbcAMP). Germinal vesicle breakdown (GVB) was stimulated by the addition of FSH. Medium was supplemented with either no macromolecule or with varying concentrations of polyvinylpyrrolidone (PVP), polyvinylalcohol (PVA), crystallized bovine serum albumin (BSA), or fetal bovine serum (FBS). Oocyte maturation in all FSH-free cultures occurred at a frequency of about 30% or below. High frequencies of maturation were achieved when FSH was added to macromolecule-free medium or to cultures containing PVP, PVA, or BSA. Crystallized BSA was the most effective of these in supporting stimulation of maturation (94% GVB at 3 mg/ml, compared with 72-74% with synthetic polymer-supplemented or macromolecule-free media). The BSA effect was not due to contaminating fatty acids, and a less pure fraction V BSA was not as effective in supporting FSH-induced maturation. FBS suppressed FSH stimulation of maturation in a dose-dependent fashion. Sera from pigs, goats, horses, and rats were also inhibitory, but bovine calf serum (BCS) permitted a high maturation frequency (80% GVB). When added to medium containing either FBS or BCS, crystallized BSA had no effect on FSH-stimulated maturation, but fraction V BSA suppressed maturation in both serum-supplemented media. Under no conditions did FSH stimulate maturation in cumulus cell-free oocytes. These results demonstrate that hormone-induced oocyte maturation is supported in vitro by nonprotein polymers as well as BSA and that the behavior of the oocyte-cumulus cell complex depends on the purity of the BSA sample. In addition, serum contains inhibitory factors that suppress the positive response to FSH. Thus, the

  14. Ovine corticotropin-releasing hormone stimulation test in patients with chronic renal failure: pharmacokinetic properties, and plasma adrenocorticotropic hormone and serum cortisol responses.

    PubMed

    Siamopoulos, K C; Eleftheriades, E G; Pappas, M; Sferopoulos, G; Tsolas, O

    1988-01-01

    The data on the status of the hypothalamic-pituitary-adrenal (HPA) axis in haemodialysis (HD) patients are conflicting. Moreover, a state reminiscent of Cushing's syndrome has been reported in this group of patients. Corticotropin-releasing hormone (CRH), that is produced by the hypothalamus and modulates the secretion of adrenocorticotropic hormone (ACTH), has been shown to be useful as a provocative test of the HPA axis. We investigated the effect of exogenous ovine CRH (oCRH) on plasma levels of ACTH and cortisol in 13 chronic HD patients. The plasma concentrations of immunoreactive CRH following oCRH administration were similar in patients and controls. In all patients, oCRH given intravenously as bolus injection caused a further increase in the already elevated levels of cortisol. The mean basal plasma levels of ACTH were within the normal range. There was, however, a blunted ACTH response to oCRH. We conclude that the HPA axis in chronic HD patients retains the ability to respond to exogenous oCRH. The patterns of the ACTH and cortisol response to this peptide resemble those observed in chronic stress (depression, anorexia nervosa). Besides, the kinetics of disappearance of oCRH indicate that the kidney may not be the major organ that metabolizes oCRH. PMID:2851525

  15. Evidence that copper-amino acid complexes are potent stimulators of the release of luteinizing hormone-releasing hormone from isolated hypothalamic granules.

    PubMed

    Barnea, A; Cho, G

    1984-09-01

    Chelated copper has been previously shown to stimulate the release of LHRH from isolated hypothalamic granules. In this study, we evaluated the chelator specificity, the kinetic constants, and the characteristics of copper interaction with LHRH granules. LHRH granules were isolated from the median eminence area of adult male rats and then incubated in a buffered medium at 37 C. Release of LHRH into the incubation medium was assessed by RIA of LHRH remaining in the granules after incubation. It was found that CuHistidine (CuHis) as well as CuCysteine markedly stimulated LHRH release from the isolated granules, release being 56% and 63%, respectively, of the total LHRH content of granules incubated in buffer alone. In contrast, neither CuGly-His-Lys nor CuBSA stimulated LHRH release. The CuHis-stimulated release of LHRH was a saturable function of the concentration of CuHis. The Michaelis-Menten constants of this release process were estimated; the apparent Km for copper was found to be 4 microM, and the maximal velocity was 65% of the granule content of LHRH released in 5 min. In addition, we noted that CuHis-stimulated release of LHRH, assessed 6 min after CuHis, was completely abolished when dithiothreitol (DTT) was added immediately after CuHis, partially abolished when added 1 or 2 min after CuHis, and not affected at all when added 3 min after CuHis. This time course of DTT inhibition of LHRH release suggests that a period of 2-3 min of copper interaction with the granules is required for the 6-min manifestation of copper action. Furthermore, this DTT-inhibitable interaction of copper did not occur when granules were incubated at 4 C. In summary the findings that copper, chelated to putative circulating chelators, markedly stimulates LHRH release and that the apparent Km of 4 microM for copper in this process is within the concentration range for the physiological action of copper support the proposal that blood-borne copper can interact rapidly with the LHRH

  16. Stimulating effect of glycoprotein hormone free alpha-subunit and daily gonadotropin releasing hormone treatment on prolactin release from 50-day ovine foetal pituitary explants.

    PubMed

    Chabot, V; Gauthier, C; Combarnous, Y; Taragnat, C

    2001-02-01

    The aim of our study was to determine whether free alpha of glycoprotein hormones (free alpha) plays a role in lactotroph function during early pituitary development in the sheep foetus. Detection and quantification of free alpha, luteinzing hormone beta-subunit (LHbeta) and prolactin immunolabelling were determined by immunocytochemistry at days 32, 37, 42, 50 and 63 of gestation. Free alpha- and LHbeta-containing cells were first detected in the ovine foetal pituitary gland on day 37 of gestation, while prolactin-containing cells were first identified on day 42. Analysis of serial sections suggested that free alpha immunoreactive cells were also LHbeta-positive, indicating that free alpha was mainly synthesized by gonadotrophs. In early foetal stages, free alpha occurred in the antero-medio ventral region of the pituitary gland, whereas prolactin-containing cells were more dorsally and more caudally localized. The free alpha-, LHbeta- and prolactin-immunostained area increased markedly between days 50 and 63 of gestation. To evaluate a possible functional relationship between gonadotrophs and lactotrophs, the effects of free alpha or gonadotropin releasing hormone (GnRH) on prolactin release were assayed. Chronic treatment of pituitary explants from male and female 42-day-old ovine foetuses for 8 days with 10-9 or 10-7 M ovine free alpha did not affect prolactin release. By contrast, free alpha administration on pituitary explants from male and female 50-day-old foetuses resulted in enhanced prolactin release. At this age, a daily (2 h per day) treatment with 10-8 M GnRH had similar stimulatory effect to free alpha whereas a 'first day' treatment (24 h on the first day) reduced prolactin release throughout the culture in males and had no effect in females. These results indicate that, despite early detection of free alpha at day 37 in the ovine foetal pituitary, its stimulatory effect on prolactin release occurs from day 50 of gestation, corresponding to the

  17. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    SciTech Connect

    Rettori, V.; Aguila, M.C.; McCann, S.M. ); Gimeno, M.F.; Franchi, A.M. )

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  18. Follicular dynamics in Mangalarga mares.

    PubMed

    Buratini, J; Rosa e Silva, A A; Barros, C M; Papa, F O; Caldas, M C; Meira, C

    1997-12-01

    Ovarian follicular activity was studied by ultrasonography during 17 oestrous cycles in 9 Mangalarga mares during the second half of the ovulatory season. Sixteen oestrous cycles were considered normal and one 3-wave cycle showing a prolonged luteal phase was considered atypical. Daily ultrasonographic examinations were performed and the compiled data on follicular dynamics were studied retrospectively. One major wave of follicular growth was observed in 13 of the 16 normal cycles (81.25%), whereas 2 major waves occurred in 3 cycles (18.75%). The mean (+/- s.d.) days of emergence of the primary wave of follicular development in cycles containing one or 2 waves were Day 6.0 +/- 2.3 and Day 11.0 +/- 1.0, respectively. The secondary wave of follicular development in 2-wave cycles emerged on Day 0.0 +/- 3.6. The day of wave divergence for primary waves of follicular development in cycles which exhibited one or 2 major waves were Day 12.2 +/- 3.5 and Day 17.3 +/- 3.0, respectively. Divergence of secondary waves occurred in only one of the 3 cycles which exhibited 2 major follicular waves (Day 7). The mean (+/- s.d.) maximum diameters of the dominant follicle in the primary wave of oestrous cycles exhibiting one and 2 major waves were 39.0 +/- 3.9 mm and 34.7 +/- 2.5 mm, respectively. The mean (+/- s.d.) maximum diameter of the dominant follicle present in the secondary wave was 34.3 +/- 11.0 mm. The mean (+/- s.d.) lengths of the interovulatory intervals for cycles containing one and 2 major waves were 19.4 +/- 2.2 and 23.3 +/- 2.5 days, respectively. These data indicate that most Mangalarga mares show one major follicular wave during the oestrous cycle but a small percentage of mares show 2 major waves. PMID:9593519

  19. Melanoma-targeting properties of (99m)technetium-labeled cyclic alpha-melanocyte-stimulating hormone peptide analogues.

    PubMed

    Chen, J; Cheng, Z; Hoffman, T J; Jurisson, S S; Quinn, T P

    2000-10-15

    Preliminary reports have demonstrated that (99m)technetium (Tc)-labeled cyclic [Cys(3,4,10), D-Phe7]alpha-MSH(3-13) (CCMSH) exhibits high tumor uptake and retention values in a murine melanoma mouse model. In this report, the tumor targeting mechanism of 99mTc-CCMSH was studied and compared with four other radiolabeled alpha-melanocyte stimulating hormone (alpha-MSH) peptide analogues: 125I-(Tyr2)-[Nle4, D-Phe7]alpha-MSH [125I-(Tyr2)-NDP]; 99mTc-CGCG-NDP; 99mTc-Gly11-CCMSH; and 99mTc-Nle11-CCMSH. In vitro receptor binding, internalization, and cellular retention of radiolabeled alpha-MSH analogues in B16/F1 murine cell line demonstrated that >70% of the receptor-bound radiolabeled analogues were internalized together with the receptor. Ninety % of the internalized 125I-(Tyr2)-NDP, whereas only 36% of internalized 99mTc-CCMSH, was released from the cells into the medium during a 4-h incubation at 37 degrees C. Two mouse models, C57 mice and severe combined immunodeficient (Scid) mice, inoculated s.c. with B16/F1 murine and TXM-13 human melanoma cells were used for the in vivo studies. Tumor uptake values of 11.32 and 2.39 [% injected dose (ID)/g] for 99mTc-CCMSH at 4 h after injection, resulted in an uptake ratio of tumor:blood of 39.0 and 11.5 in murine melanoma-C57 and human melanoma-Scid mouse models, respectively. Two strategies for decreasing the nonspecific kidney uptake of 99mTc-CCMSH, substitution of Lys11 in CCMSH with Gly11 or Nle11, and lysine coinjection, were evaluated. The biodistribution data for the modified peptides showed that Lys11 replacement dramatically decreased the kidney uptake, whereas the tumor uptakes of 99mTc-Nle11- and 99mTc-Gly11-CCMSH were significantly lower than that of 99mTc-CCMSH. Lysine coinjection significantly decreased the kidney uptake (e.g., from 14.6% ID/g to 4.5% ID/g at 4 h after injection in murine melanoma-C57 mice) without significantly changing the value of tumor uptake of 99mTc-CCMSH. In conclusion, the compact

  20. 64Cu-labeled alpha-melanocyte-stimulating hormone analog for microPET imaging of melanocortin 1 receptor expression.

    PubMed

    Cheng, Zhen; Xiong, Zhengming; Subbarayan, Murugesan; Chen, Xiaoyuan; Gambhir, Sanjiv Sam

    2007-01-01

    The alpha-melanocyte-stimulating hormone (alpha-MSH) receptor (melanocortin type 1 receptor, or MC1R) plays an important role in the development and growth of melanoma cells. It was found that MC1R was overexpressed on most murine and human melanoma, making it a promising molecular target for melanoma imaging and therapy. Radiolabeled alpha-MSH peptide and its analogs that can specifically bind with MC1R have been extensively explored for developing novel agents for melanoma detection and radionuclide therapy. The goal of this study was to evaluate a 64Cu-labeled alpha-MSH analog, Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys(DOTA)-NH2 (DOTA-NAPamide), as a potential molecular probe for microPET imaging of melanoma and MC1R expression in melanoma xenografted mouse models. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugated NAPamide was synthesized and radiolabeled with 64Cu (t1/2=12 h) in NH4OAc (0.1 M; pH 5.5) buffered solution for 60 min at 50 degrees C. Cell culture studies reveal rapid and high uptake and internalization of 64Cu-DOTA-NAPamide in B16F10 cells. Over 90% of receptor-bound tracer is internalized at 3 h incubation. A cellular retention study demonstrates that the receptor-bound 64Cu-DOTA-NAPamide is slowly released from the B16F10 cells into the medium; 66% of the radioactivity is still associated with the cells even after 3 h incubation. The biodistribution of 64Cu-DOTA-NAPamide was then investigated in C57BL/6 mice bearing subcutaneous murine B16F10 melanoma tumors with high capacity of MC1R and Fox Chase Scid mice bearing human A375M melanoma with a relatively low number of MC1R receptors. Tumor uptake values of 64Cu-DOTA-NAPamide are found to be 4.63 +/- 0.45% and 2.49 +/- 0.31% ID/g in B16F10 and A375M xenografted melanoma at 2 h postinjection (pi), respectively. The B16F10 tumor uptake at 2 h pi is further inhibited to 2.29 +/- 0.24% ID/g, while A375M tumor uptake at 2 h pi remains 2.20 +/- 0.41% ID/g with a coinjection of excess

  1. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    SciTech Connect

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  2. Review on mechanisms of dairy summer infertility and implications for hormonal intervention.

    PubMed

    Wakayo, B U; Brar, P S; Prabhakar, S

    2015-01-01

    In dairy cows and buffaloes, summer heat stress (HS) reduces milk yield and delays return to pregnancy leading to financial loss. Clues for effective interventions against summer infertility (SI) lie in understanding the underlying mechanisms. This article reviews current knowledge on the mechanisms of bovine SI and their implication for hormonal management. Under HS dairy animals encounter anestrous, silent cycles and repeat breeding which extend their open period. These effects are attributed mainly to HS induced disturbances in luteinizing hormone (LH) secretion, follicular dominance and estrogen secretion, ovulation and oocyte competence, luteal development and progesterone secretion, utero-placental function and embryo-fetal development. Hormonal timed artificial insemination protocols and LH support around estrous improved summer pregnancy rates by avoiding need for estrus detection, assisting follicular development and ovulation, enhancing quality oocytes and stimulating luteal function. Progesterone supplementation to enhance embryonic development did not produce significant improvement in summer pregnancy rates. There is need for evaluating integrated approaches combining hormones, metabolic modifier and cyto-protective agents. PMID:26623355

  3. Effective Mobilization of Very Small Embryonic-Like Stem Cells and Hematopoietic Stem/Progenitor Cells but Not Endothelial Progenitor Cells by Follicle-Stimulating Hormone Therapy

    PubMed Central

    Zbucka-Kretowska, Monika; Eljaszewicz, Andrzej; Lipinska, Danuta; Grubczak, Kamil; Rusak, Malgorzata; Mrugacz, Grzegorz; Dabrowska, Milena; Ratajczak, Mariusz Z.; Moniuszko, Marcin

    2016-01-01

    Recently, murine hematopoietic progenitor stem cells (HSCs) and very small embryonic-like stem cells (VSELs) were demonstrated to express receptors for sex hormones including follicle-stimulating hormone (FSH). This raised the question of whether FSH therapy at clinically applied doses can mobilize stem/progenitor cells in humans. Here we assessed frequencies of VSELs (referred to as Lin−CD235a−CD45−CD133+ cells), HSPCs (referred to as Lin−CD235a−CD45+CD133+ cells), and endothelial progenitor cells (EPCs, identified as CD34+CD144+, CD34+CD133+, and CD34+CD309+CD133+ cells) in fifteen female patients subjected to the FSH therapy. We demonstrated that FSH therapy resulted in statistically significant enhancement in peripheral blood (PB) number of both VSELs and HSPCs. In contrast, the pattern of responses of EPCs delineated by different cell phenotypes was not uniform and we did not observe any significant changes in EPC numbers following hormone therapy. Our data indicate that FSH therapy mobilizes VSELs and HSPCs into peripheral blood that on one hand supports their developmental origin from germ lineage, and on the other hand FSH can become a promising candidate tool for mobilizing HSCs and stem cells with VSEL phenotype in clinical settings. PMID:26635885

  4. Effective Mobilization of Very Small Embryonic-Like Stem Cells and Hematopoietic Stem/Progenitor Cells but Not Endothelial Progenitor Cells by Follicle-Stimulating Hormone Therapy.

    PubMed

    Zbucka-Kretowska, Monika; Eljaszewicz, Andrzej; Lipinska, Danuta; Grubczak, Kamil; Rusak, Malgorzata; Mrugacz, Grzegorz; Dabrowska, Milena; Ratajczak, Mariusz Z; Moniuszko, Marcin

    2016-01-01

    Recently, murine hematopoietic progenitor stem cells (HSCs) and very small embryonic-like stem cells (VSELs) were demonstrated to express receptors for sex hormones including follicle-stimulating hormone (FSH). This raised the question of whether FSH therapy at clinically applied doses can mobilize stem/progenitor cells in humans. Here we assessed frequencies of VSELs (referred to as Lin(-)CD235a(-)CD45(-)CD133(+) cells), HSPCs (referred to as Lin(-)CD235a(-)CD45(+)CD133(+) cells), and endothelial progenitor cells (EPCs, identified as CD34(+)CD144(+), CD34(+)CD133(+), and CD34(+)CD309(+)CD133(+) cells) in fifteen female patients subjected to the FSH therapy. We demonstrated that FSH therapy resulted in statistically significant enhancement in peripheral blood (PB) number of both VSELs and HSPCs. In contrast, the pattern of responses of EPCs delineated by different cell phenotypes was not uniform and we did not observe any significant changes in EPC numbers following hormone therapy. Our data indicate that FSH therapy mobilizes VSELs and HSPCs into peripheral blood that on one hand supports their developmental origin from germ lineage, and on the other hand FSH can become a promising candidate tool for mobilizing HSCs and stem cells with VSEL phenotype in clinical settings. PMID:26635885

  5. Pregnancy-associated plasma protein-a production in rat granulosa cells: stimulation by follicle-stimulating hormone and inhibition by the oocyte-derived bone morphogenetic protein-15.

    PubMed

    Matsui, Motozumi; Sonntag, Barbara; Hwang, Seong Soo; Byerly, Tara; Hourvitz, Ariel; Adashi, Eli Y; Shimasaki, Shunichi; Erickson, Gregory F

    2004-08-01

    Pregnancy-associated plasma protein-A (PAPP-A) is the major IGF binding protein-4 (IGFBP-4) protease in follicular fluid, consistent with its proposed role in folliculogenesis. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. Here we show that FSH and oocytes regulate PAPP-A expression in granulosa cells (GCs). By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles. To explore the mechanism, we used primary cultures of rat GCs. Control (untreated) cells produced little or no PAPP-A spontaneously. Conversely, FSH markedly stimulated PAPP-A mRNA and protein in a dose- and time-dependent fashion. Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes. To investigate the nature of the inhibition, we tested the effect of oocyte-derived bone morphogenetic protein-15 (BMP-15). BMP-15 alone had no effect on basal levels of PAPP-A expression by cultures of membrana GCs or CGCs. However, BMP-15 markedly inhibited the FSH stimulation of PAPP-A production in a dose-dependent manner. The cleavage of IGFBP-4 by conditioned media from FSH-treated GCs was completely inhibited by anti-PAPP-A antibody, indicating the IGFBP-4 protease secreted by GCs is PAPP-A. These results demonstrate stimulatory and inhibitory roles for FSH and BMP-15, respectively, in regulating PAPP-A production by GCs. We propose that FSH and oocyte-derived BMP-15 form a controlling network that ensures the spatiotemporal pattern of GC PAPP-A expression in the dominant follicle. PMID:15087430

  6. Evidence for a daily rhythmicity in the acute release of luteinizing hormone in response to electrical stimulation in the Japanese quail.

    PubMed

    Konishi, H; Foster, R G; Follett, B K

    1987-08-01

    This study was undertaken to examine the effect of electrical stimulation of the hypothalamus at different times of day on luteinizing hormone (LH) secretion in male castrated quail on short days (8L:16D). The posterior hypothalamus was stimulated with square-wave pulses of 80 microA for 2 min through chronically-implanted platinum microelectrodes. Stimulation was carried out on each quail at 4 (treatment A), 10 (B), or 14 h (C) after dawn. Plasma LH levels were increased markedly within 2 min of ending the stimulation but reached basal levels again over the next 20 min or so. The absolute increase was significantly greater in treatment B (10 h after lights on) than at the other times tested. This is consistent with a rhythm in hypothalamic responsivity. The results are discussed in the context of the rhythm of photoinducibility which occurs early in the night and which is used by quail as a photoperiodic clock to regulate seasonal reproduction. PMID:3625579

  7. Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer.

    PubMed

    Zhang, John

    2016-01-01

    Minimal stimulation in vitro fertilization (mini-IVF) consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC), gonadotropin releasing hormone (GnRH) ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author's own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS). Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort. PMID:27441046

  8. Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer

    PubMed Central

    Zhang, John

    2016-01-01

    Minimal stimulation in vitro fertilization (mini-IVF) consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC), gonadotropin releasing hormone (GnRH) ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author’s own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS). Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort. PMID:27441046

  9. Effects of new sports tennis type exercise on aerobic capacity, follicle stimulating hormone and N-terminal telopeptide in the postmenopausal women

    PubMed Central

    Shin, Hyun-Jae; Lee, Ha-Yan; Cho, Hye-Young; Park, Yun-Jin; Moon, Hyung-Hoon; Lee, Sung-Hwan; Lee, Sung-Ki; Kim, Myung-Ki

    2014-01-01

    Menopause is characterized by rapid decreases in bone mineral density, aerobic fitness, muscle strength, and balance. In the present study, we investigated the effects of new sports tennis type exercise on aerobic capacity, follicle stimulating hormone (FSH) and N-terminal telopeptide (NTX) in the postmenopausal women. Subjects were consisted of 20 postmenopausal women, who had not menstruated for at least 1 yr and had follicle-stimulating hormone levels > 35 mIU/L, estradiol levels< 40 pg/mL. The subjects were randomly divided into two groups: control group (n= 10), new sports tennis type exercise group (n= 10). New sports tennis type exercise was consisted of warm up (10 min), new sports tennis type exercise (40 min), cool down (10 min) 3 days a per week for 12 weeks. The aerobic capacities were increased by 12 weeks new sports tennis type exercise. New sports tennis type exercise significantly increased FSH and NTx levels, indicating biochemical markers of bone formation and resorption. These findings indicate that 12 weeks of new sports tennis type exercise can be effective in prevention of bone loss and enhancement of aerobic capacity in postmenopausal women. PMID:24877043

  10. Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats: Roles of Neuropeptide Y and α-Melanocyte-Stimulating Hormone.

    PubMed

    Shi, Zhigang; Cassaglia, Priscila A; Gotthardt, Laura C; Brooks, Virginia L

    2015-12-01

    Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose-anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte-stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte-stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus. PMID:26483343

  11. Renal functional reserve in pigs: renal haemodynamics, renal tubular function and salt and water homeostatic hormones during amino acid and dopamine stimulation.

    PubMed

    Poulsen, E U; Frøkiaer, J; Jørgensen, T M; Pedersen, E B; Rehling, M

    1997-01-01

    The purpose of the study was to evaluate renal functional reserve [RFR is the difference between glomerular filtration rate (GFR) at rest and maximal GFR after stimulation] in a controlled study in normal pigs. Our basic hypothesis was that a decreased RFR may be used as an early indicator of renal deterioration, i.e. a test to disclose significant obstruction as opposed to simple dilatation in hydronephrosis. During various forms of stimulation (amino acids, captopril and dopamine), we measured changes in GFR, renal plasma flow (RPF), tubular reabsorption of sodium and water, net uptake from plasma to the kidney of three salt and water homeostatic hormones (angiotensin II, aldosterone and atrial natriuretic peptide) and of glucagon, which is thought to play a key role as mediator of the GFR increase during amino acid infusion. We found the largest GFR increase during combined infusion of amino acids and dopamine (+13%), but compared with a non-stimulated control group, the GFR increase was statistically non-significant. RPF increased by 57% during stimulation with amino acids plus dopamine (P < 0.001), while tubular reabsorption of sodium and water, and renal uptake of angiotensin II, aldosterone and atrial natriuretic peptide showed no significant differences between control and stimulation groups. The renal uptake of glucagon increased significantly during amino acid stimulation with no concomitant GFR increase. We conclude that in this experimental, non-obstructed model, RFR is a very insensitive measure, which cannot be used to discriminate between obstruction and simple dilatation in hydronephrosis. Further, our study does not support the hypothesis that glucagon is involved in GFR changes after amino acids. PMID:9015658

  12. Follicular Dendritic Cell Sarcoma

    PubMed Central

    Udayakumar, Achandira M.; Al-Bahri, Maiya; Burney, Ikram A.; Al-Haddabi, Ibrahim

    2015-01-01

    Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors’ knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour. PMID:26355964

  13. Ovarian follicular dynamics after aromatizable or non aromatizable neonatal androgenization.

    PubMed

    Anesetti, Gabriel; Chávez-Genaro, Rebeca

    2016-10-01

    The effects of neonatal testosterone or dihydrotestosterone exposure on ovarian follicular dynamics were analysed at prepubertal, pubertal or adult age in Wistar rats. Both androgens induced a transitory increase on follicular endowment that was partially corrected at puberty. At adult age testosterone prevented ovulation, without significant modifications on follicular dynamics. An increased number of cystic structures were observed from puberty to adult age. However, ovaries of rats treated with dihydrotestosterone showed follicles with evident morphological alterations in granulosa and thecal layers although several corpora lutea were observed. A significant increase in preantral follicles and few cystic structures were detected at advanced adulthood. The size of cyst increased with age. No immunohistochemical changes on growth factors or enzymes related to steroidogenesis in growing follicles were obvious in any group. In both androgenized groups, cysts shared immunohistochemical characteristics exhibited by preovulatory follicles but they were unable to ovulate spontaneously. Our results provide an insight into the role of different androgens in female reproductive system development, indicating a direct effect of dihydrotestosterone on ovarian tissues whereas a central effect would be the main feature of neonatal testosterone exposure. Heterogeneous clinical manifestations seen in pathologies such as polycystic ovary syndrome among women could be associated with subtle hormonal changes during follicular population development. PMID:27541036

  14. Serotonin interferes with Ca2+ and PKC signaling to reduce gonadotropin-releasing hormone-stimulated GH secretion in goldfish pituitary cells.

    PubMed

    Yu, Yi; Wong, Anderson O L; Chang, John P

    2008-10-01

    In goldfish, two endogenous gonadotropin-releasing hormones (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), are thought to stimulate growth hormone (GH) release via protein kinase C (PKC) and subsequent increases in intracellular Ca(2+) levels ([Ca(2+)](i)). In contrast, the signaling mechanism for serotonin (5-HT) inhibition of GH secretion is still unknown. In this study, whether 5-HT inhibits GH release by actions at sites along the PKC and Ca(2+) signal transduction pathways leading to hormone release were examined in primary cultures of goldfish pituitary cells. Under static incubation and column perifusion conditions, 5-HT reduced basal, as well as sGnRH- and cGnRH-II-stimulated, GH secretion. 5-HT also suppressed GH responses to two PKC activators but had no effect on the GH-releasing action of the Ca(2+) ionophore ionomycin. Ca(2+)-imaging studies with identified somatotropes revealed that 5-HT did not alter basal [Ca(2+)](i) but attenuated the magnitude of the [Ca(2+)](i) responses to the two GnRHs. Prior treatment with 5-HT and cGnRH-II reduced the magnitude of the [Ca(2+)](i) responses induced by depolarizing levels of K(+). Similar inhibition, however, was not observed with prior treatment of 5-HT and sGnRH. These results suggest that 5-HT, by direct actions at the somatotrope level, interferes with PKC and Ca(2+) signaling pathways to reduce the GH-releasing effect of GnRH. 5-HT action may occur at the level of PKC activation or its downstream signaling events prior to the subsequent rise in [Ca(2+)](i.). The differential Ca(2+) responses by depolarizing doses of K(+) is consistent with our previous findings that sGnRH and cGnRH-II are coupled to overlapping and yet distinct Ca(2+)-dependent mechanisms. PMID:18723020

  15. Neuromedin U partly mimics thyroid-stimulating hormone and triggers Wnt/β-catenin signalling in the photoperiodic response of F344 rats.

    PubMed

    Helfer, G; Ross, A W; Morgan, P J

    2013-12-01

    In seasonal animals, photoperiod exerts profound effects on physiology, such as growth, energy balance and reproduction, via changes in the neuroendocrine axes. A key element of the photoperiodic response is the thyroid hormone level in the hypothalamus, which is controlled via retrograde transport of thyroid-stimulating hormone (TSH) from the pars tuberalis of the pituitary. TSH regulates type II deiodinase (Dio2) expression, which transforms inactive thyroid hormone to its active form, via TSH receptors expressed in the ependymal cells of the hypothalamus. In the present study, we hypothesised that a second peptide hormone, neuromedin U (NMU), may play a role in the photoperiodic response alongside TSH because the gene for NMU is also expressed in a strongly photoperiod-dependent manner in the pars tuberalis and its receptor NMU2 is expressed in the ependymal layer of the third ventricle in photoperiod-sensitive F344 rats. Consistent with other studies conducted in nonseasonal mammals, we found that acute i.c.v. injections of NMU into the hypothalamus negatively regulated food intake and body weight and increased core body temperature in F344 rats. At the same time, NMU increased Dio2 mRNA expression in the ependymal region of the hypothalamus similar to the effects of TSH. These data suggest that NMU may affect acute and photoperiodically controlled energy balance through distinct pathways. We also showed that TSH inhibits the expression of type III deiodinase (Dio3) in F344 rats, a response not mimicked by NMU. Furthermore, NMU also increased the expression of genes from the Wnt/β-catenin pathway within the ependymal layer of the third ventricle. This effect was not influenced by TSH. These data indicate that, although NMU acts with some similarities to TSH, it also has completely distinct signalling functions that do not overlap. In summary, the present study of NMU signalling reveals the potential for a new player in the control of seasonal biology. PMID

  16. Neuromedin U Partly Mimics Thyroid-Stimulating Hormone and Triggers Wnt/β-Catenin Signalling in the Photoperiodic Response of F344 Rats

    PubMed Central

    Helfer, G; Ross, A W; Morgan, P J

    2013-01-01

    In seasonal animals, photoperiod exerts profound effects on physiology, such as growth, energy balance and reproduction, via changes in the neuroendocrine axes. A key element of the photoperiodic response is the thyroid hormone level in the hypothalamus, which is controlled via retrograde transport of thyroid-stimulating hormone (TSH) from the pars tuberalis of the pituitary. TSH regulates type II deiodinase (Dio2) expression, which transforms inactive thyroid hormone to its active form, via TSH receptors expressed in the ependymal cells of the hypothalamus. In the present study, we hypothesised that a second peptide hormone, neuromedin U (NMU), may play a role in the photoperiodic response alongside TSH because the gene for NMU is also expressed in a strongly photoperiod-dependent manner in the pars tuberalis and its receptor NMU2 is expressed in the ependymal layer of the third ventricle in photoperiod-sensitive F344 rats. Consistent with other studies conducted in nonseasonal mammals, we found that acute i.c.v. injections of NMU into the hypothalamus negatively regulated food intake and body weight and increased core body temperature in F344 rats. At the same time, NMU increased Dio2 mRNA expression in the ependymal region of the hypothalamus similar to the effects of TSH. These data suggest that NMU may affect acute and photoperiodically controlled energy balance through distinct pathways. We also showed that TSH inhibits the expression of type III deiodinase (Dio3) in F344 rats, a response not mimicked by NMU. Furthermore, NMU also increased the expression of genes from the Wnt/β-catenin pathway within the ependymal layer of the third ventricle. This effect was not influenced by TSH. These data indicate that, although NMU acts with some similarities to TSH, it also has completely distinct signalling functions that do not overlap. In summary, the present study of NMU signalling reveals the potential for a new player in the control of seasonal biology. PMID

  17. Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone.

    PubMed

    Anderson, E; Lee, M T; Lee, G Y

    1992-11-01

    Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a

  18. Noise exposure effect on testicular histology, morphology and on male steroidogenic hormone.

    PubMed

    Swami, Chandralekha G; Ramanathan, Jeganathan; Charan Jeganath, C

    2007-07-01

    The noise stress, after it passes through the hearing apparatus, not only affects the auditory apparatus but also other body functions. The alterations in the levels of cortical hormone, adrenocorticosterone, nor-epinephrine hormone (which are primarily considered as stress hormones) on follicular stimulating hormone, testosterone, and lutinizing hormone were reported in relation with stress. Male albino rats weighing 200 to 250 grams were exposed to 100 dB of noise for one hour and three hours in acute group and daily one hour exposure for 60 day, and 90 day in chronic group. The serum testosterone levels were measured in these animals. There was significant reduction in serum testosterone levels and this was similar with earlier reports. The tissues were collected for light and confocal microscopic study. 100dB of traffic noise exposure of varying duration had definite permanent effect on testicular histology and morphology and on the male sex hormone. The adaptation mechanism was noticed at the hormonal level only but the structural changes noticed were definite and permanent. The agglutinated dead sperms revealed the possibility of infertily when chronically exposed to noise stress. PMID:23515367

  19. Noise Exposure Effect on Testicular Histology, Morphology and on Male Steroidogenic Hormone

    PubMed Central

    Swami, Chandralekha G.; Ramanathan, Jeganathan; Charan Jeganath, C

    2007-01-01

    The noise stress, after it passes through the hearing apparatus, not only affects the auditory apparatus but also other body functions. The alterations in the levels of cortical hormone, adrenocorticosterone, nor-epinephrine hormone (which are primarily considered as stress hormones) on follicular stimulating hormone, testosterone, and lutinizing hormone were reported in relation with stress. Male albino rats weighing 200 to 250 grams were exposed to 100 dB of noise for one hour and three hours in acute group and daily one hour exposure for 60 day, and 90 day in chronic group. The serum testosterone levels were measured in these animals. There was significant reduction in serum testosterone levels and this was similar with earlier reports. The tissues were collected for light and confocal microscopic study. 100dB of traffic noise exposure of varying duration had definite permanent effect on testicular histology and morphology and on the male sex hormone. The adaptation mechanism was noticed at the hormonal level only but the structural changes noticed were definite and permanent. The agglutinated dead sperms revealed the possibility of infertily when chronically exposed to noise stress. PMID:23515367

  20. Ovarian stimulation in patients with breast cancer

    PubMed Central

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  1. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

    PubMed Central

    Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

    2015-01-01

    Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

  2. Stimulation of molt by RNA interference of the molt-inhibiting hormone in the crayfish Cherax quadricarinatus.

    PubMed

    Pamuru, Ramachandra R; Rosen, Ohad; Manor, Rivka; Chung, J Sook; Zmora, Nilli; Glazer, Lilah; Aflalo, Eliahu D; Weil, Simy; Tamone, Sherry L; Sagi, Amir

    2012-09-01

    In crustaceans, molting is known to be under the control of neuropeptide hormones synthesized and secreted from the eyestalk ganglia. While the role of molt-inhibiting hormone (MIH) in regulating molting has been described in several species using classical methods, an in vivo specific MIH targeted manipulation has not been described yet. In the present study, an MIH cDNA was isolated and sequenced from the eyestalk ganglia of the Australian freshwater red claw crayfish Cherax quadricarinatus (Cq) by 5' and 3' RACE. We analyzed the putative Cq-MIH based on sequence homology, a three dimensional structure model and transcript's tissue specificity. We further examined the involvement of Cq-MIH in the control of molt in the crayfish through RNAi by in vivo injections of Cq-MIH double-stranded RNA, which resulted in, similarly to eyestalk ablation, acceleration of molt cycles. This acceleration was reflected by a significant reduction (up to 32%) in molt interval and an increased rate in molt mineralization index (MMI), which correlated with the induction of ecdysteroid hormones compared to control. Altogether, this study provides a proof of function for the involvement of the Cq-MIH gene in molt regulation in the crayfish. PMID:22664421

  3. The effectiveness of recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal prior to radioiodine remnant ablation in thyroid cancer: a meta-analysis of randomized controlled trials.

    PubMed

    Pak, Kyoungjune; Cheon, Gi Jeong; Kang, Keon Wook; Kim, Seong-Jang; Kim, In-Joo; Kim, E Edmund; Lee, Dong Soo; Chung, June-Key

    2014-06-01

    We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative (131)I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW. PMID:24932083

  4. CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle-stimulating hormone and transforming growth factor β1 upregulation of steroidogenesis.

    PubMed

    Fang, Wei-Ling; Lee, Ming-Ting; Wu, Leang-Shin; Chen, Yun-Ju; Mason, Jian; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

    2012-06-01

    In vitro and in vivo studies implicate that follicle-stimulating hormone (FSH) and transforming growth factor β1 (TGFβ1) play crucial physiological roles in regulating ovarian granulosa cell function essential to fertility control in females. FSH induces cAMP and calcium signaling, thereby activating transcription factor CREB to upregulate steroidogenic gene expression, and TGFβ1 greatly enhances FSH-stimulated steroidogenesis. A CREB coactivator CRTC2/TORC2 was identified to function as a cAMP and calcium-sensitive coincidence sensor. This led us to explore the role of CRTC2 and its regulator calcineurin in FSH and TGFβ1-stimulated steroidogenesis. Primary culture of granulosa cells from gonadotropin-primed immature rats was used. Immunoblotting analysis shows that FSH rapidly and transiently induced dephosphorylation/activation of CRTC2, and FSH + TGFβ1 additionally induced late-phase CRTC2 dephosphorylation. Immunofluorescence analysis further confirms FSH ± TGFβ1 promoted CRTC2 nuclear translocation. Using selective inhibitors, we demonstrate that FSH activated CRTC2 in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor (TGFβRI)-modulated FSH action in a calcineurin-mediated and PKA-independent fashion. Next, we investigated the involvement of calcineurin and CRTC2 in FSH and TGFβ1-stimulated steroidogenesis. Calcineurin and TGFβRI inhibitor dramatically reduced the FSH ± TGFβ1-increased progesterone synthesis and protein levels of StAR, P450scc, and 3β-HSD enzyme. Furthermore, chromatin-immunoprecipitation and immunoprecipitation analyses demonstrate that FSH ± TGFβ1 differentially increased CRTC2, CREB, and CBP binding to these steroidogenic genes, and CREB nuclear association with CRTC2 and CBP. In all, this study reveals for the first time that CRTC2 and calcineurin are critical signaling mediators in FSH and TGFβ1-stimulated steroidogenesis in ovarian granulosa cells. PMID:21826657

  5. The role of LH in ovarian stimulation: exogenous LH: let's design the future.

    PubMed

    Lévy, D P; Navarro, J M; Schattman, G L; Davis, O K; Rosenwaks, Z

    2000-11-01

    Historically, follicular stimulation protocols have included both FSH and LH in an attempt to mimic the physiology of normal human folliculogenesis. However, many recent gonadotrophin administration regimens have completely eliminated LH bioactivity. The importance and the amount of LH necessary for optimal follicular stimulation has been a topic of debate. Several recent studies have added to our understanding of the actions of androgens, oestrogens, gonadotrophins, and insulin on the follicle-oocyte unit, allowing a less speculative approach. Moreover, the availability of human gonadotrophins synthesized by recombinant DNA technology and gonadotrophin-releasing hormone (GnRH) antagonists, should soon permit a precise in-vivo assessment and re-evaluation of the historical 2-cell, two-gonadotrophin hypothesis. These pharmacological tools may also provide essential insights into the physiological roles of FSH and LH in human follicular development and oocyte maturation. The recombinant gonadotrophins give clinicians the unique opportunity to tailor ovarian stimulation regimens according to the patient's medical history, in an effort both to maximize oocyte yield and to improve oocyte quality. PMID:11056116

  6. Low reversibility of intracellular cAMP accumulation in mouse Leydig tumor cells (MLTC-1) stimulated by human Luteinizing Hormone (hLH) and Chorionic Gonadotropin (hCG).

    PubMed

    Klett, Danièle; Meslin, Philippine; Relav, Lauriane; Nguyen, Thi Mong Diep; Mariot, Julie; Jégot, Gwenhaël; Cahoreau, Claire; Combarnous, Yves

    2016-10-15

    In order to study the intracellular cAMP response kinetics of Leydig cells to hormones with LH activity, we used MLTC-1 cells transiently expressing a chimeric cAMP-responsive luciferase so that real-time variations of intracellular cAMP concentration could be followed using oxiluciferin luminescence produced from catalyzed luciferin oxidation. The potencies of the different LHs and CGs were evaluated using areas under the curves (AUC) of their kinetics over 60 min stimulation. All mammalian LHs and CGs tested were found to stimulate cAMP accumulation in these cells. The reversibility of this stimulation was studied by removing the hormone from the culture medium after 10 min of incubation. The ratios of kinetics AUC after removing or not the hormone were used to evaluate the stimulation reversibility of each hormone. Natural and recombinant hLHs and hCGs were found to exhibit slowly reversible activation compared to pituitary rat, ovine, porcine, camel and equine LHs, serum-derived eCG (PMSG) and recombinant eLH/CGs. Carbohydrate side chains are not involved in this phenomenon since natural and recombinant homologous hormones exhibit the same reversibility rates. It is still unknown whether only one human subunit, α or β, is responsible for this behaviour or whether it is due to a particular feature of the hLH and hCG quaternary structure. PMID:27373440

  7. Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase*

    PubMed Central

    Cottom, Joshua; Salvador, Lisa M.; Maizels, Evelyn T.; Reierstad, Scott; Park, Youngkyu; Carr, Daniel W.; Davare, Monika A.; Hell, Johannes W.; Palmer, Stephen S.; Dent, Paul; Kawakatsu, Hisaaki; Ogata, Masato; Hunzicker-Dunn, Mary

    2006-01-01

    In this report we sought to elucidate the mechanism by which the follicle-stimulating hormone (FSH) receptor signals to promote activation of the p42/p44 extracellular signal-regulated protein kinases (ERKs) in granulosa cells. Results show that the ERK kinase MEK and upstream intermediates Raf-1, Ras, Src, and L-type Ca2+ channels are already partially activated in vehicle-treated cells and that FSH does not further activate them. This tonic stimulatory pathway appears to be restrained at the level of ERK by a 100-kDa phosphotyrosine phosphatase that associates with ERK in vehicle-treated cells and promotes dephosphorylation of its regulatory Tyr residue, resulting in ERK inactivation. FSH promotes the phosphorylation of this phosphotyrosine phosphatase and its dissociation from ERK, relieving ERK from inhibition and resulting in its activation by the tonic stimulatory pathway and consequent translocation to the nucleus. Consistent with this premise, FSH-stimulated ERK activation is inhibited by the cell-permeable protein kinase A-specific inhibitor peptide Myr-PKI as well as by inhibitors of MEK, Src, a Ca2+ channel blocker, and chelation of extracellular Ca2+. These results suggest that FSH stimulates ERK activity in immature granulosa cells by relieving an inhibition imposed by a 100-kDa phosphotyrosine phosphatase. PMID:12493768

  8. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells

    PubMed Central

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-01-01

    Previous research showed that resveratrol (trans-3,4′,5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4′,5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  9. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells.

    PubMed

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-06-01

    Previous research showed that resveratrol (trans-3,4',5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4',5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  10. Follicular Unit Extraction Hair Transplant

    PubMed Central

    Dua, Aman; Dua, Kapil

    2010-01-01

    Hair transplantation has come a long way from the days of Punch Hair Transplant by Dr. Orentreich in 1950s to Follicular Unit Hair Transplant (FUT) of 1990s and the very recent Follicular Unit Extraction (FUE) technique. With the advent of FUE, the dream of ‘no visible scarring’ in the donor area is now looking like a possibility. In FUE, the grafts are extracted as individual follicular units in a two-step or three-step technique whereas the method of implantation remains the same as in the traditional FUT. The addition of latest automated FUE technique seeks to overcome some of the limitations in this relatively new technique and it is now possible to achieve more than a thousand grafts in one day in trained hands. This article reviews the methodology, limitations and advantages of FUE hair transplant. PMID:21031064

  11. Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs.

    PubMed

    Ponglowhapan, S; Church, D B; Scaramuzzi, R J; Khalid, M

    2007-01-15

    In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The

  12. Effects of ionizing radiation and pretreatment with (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

    1987-10-01

    To assess the effects of a gonadotropin-releasing hormone agonist, (D-Leu6,des-Gly10) luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

  13. Increased abundance of aromatase and follicle stimulating hormone receptor mRNA and decreased insulin-like growth factor-2 receptor mRNA in small ovarian follicles of cattle selected for twin births.

    PubMed

    Echternkamp, S E; Aad, P Y; Eborn, D R; Spicer, L J

    2012-07-01

    follicles of Twinners support the hypothesis that increased follicular development and steroidogenesis in Twinner females result from increased extra-ovarian IGF-1 production. Furthermore, a reduction in follicular IGF2R mRNA expression accompanied by a reduction in receptor numbers would increase availability of free IGF-2 and its stimulation of follicular development in Twinners. PMID:22266997

  14. Hyposmolar stimulation of in vitro pituitary secretion of luteinizing hormone: a potential clue to the secretory process.

    PubMed

    Greer, M A; Greer, S E; Opsahl, Z; McCafferty, L; Maruta, S

    1983-10-01

    Diluting the perifusion medium with water caused a striking prompt increase in LH secretion from perifused, acutely dispersed adenohypophseal cells. The minimum effective proportion of water was 4%; the quantity of hormone secreted was proportional to the dilution of the medium up to greater than 50% water. Secretion was not induced if the dilution was made with 5% aqueous mannitol to maintain isotonicity. The LH secretory responses to hyposmolarity or to LHRH were qualitatively indistinguishable. We suggest that expansion of the outer cell membrane may be an important initial component of the mechanism of secretion from adenohypophyseal cells. PMID:6413197

  15. Inverted follicular keratosis successfully treated with imiquimod.

    PubMed

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  16. Inverted follicular keratosis successfully treated with imiquimod

    PubMed Central

    Karadag, Ayse Serap; Ozlu, Emin; Uzuncakmak, Tugba Kevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant

    2016-01-01

    Inverted follicular keratosis is a rare benign tumor of the follicular infundibulum characterized by exo-endophytic growing. It is thought to be a rare variant of the seborrheic keratosis. The diagnosis of inverted follicular keratosis is generally established histopathologically because clinical differentiation from other lesions is difficult. Herein, we present one such rare case, successfully treated with topical 5% imiquimod cream. PMID:27294052

  17. Synthetic peptides based upon a three-dimensional model for the receptor recognition site of follicle-stimulating hormone exhibit antagonistic or agonistic activity at low concentrations.

    PubMed Central

    Hage-van Noort, M; Puijk, W C; Plasman, H H; Kuperus, D; Schaaper, W M; Beekman, N J; Grootegoed, J A; Meloen, R H

    1992-01-01

    Follicle-stimulating hormone (follitropin, FSH) belongs to a group of closely related glycoprotein hormones that contain two noncovalently linked dissimilar subunits designated alpha and beta. By using synthetic peptides, several receptor interaction sites in these hormones have been identified; however, the peptides have a reduced potency (lowest effective concentration of 10(-4) to 10(-5) M) relative to the hormone itself (10(-8) to 10(-11) M). This suggests that the peptides represent only a portion of a larger recognition site in the intact hormone that comprises parts of both the beta and the alpha chains. To develop peptides that exhibit FSH-antagonistic activity at low concentrations, we have constructed a three-dimensional model for FSH, which is based on an alignment of both the beta and the alpha chains of glycoprotein hormones with thioredoxin, for which x-ray diffraction data are available. This model resulted in the prediction of a conformational receptor-binding site in FSH, in which (parts of) three earlier proposed binding regions on the FSH molecule [namely, the regions FSH alpha-(34-37), with the amino acid sequence SRAY; FSH beta-(40-43), with the amino acid sequence TRDL; and FSH beta-(87-94), the "determinant loop" with the amino acid sequence CDSDSTDC] are located within 10 A of one another. On the basis of this model, peptides have been synthesized in which two of these binding regions are linked by a synthetic amino acid whose length was derived from the model, Ac-TDSDS-NH-(CH2)5-CO-SRAY-NH2 and Ac-SRAY-NH-(CH2)4-CO-TRDL-NH2. Both peptides inhibited FSH-induced cAMP production in Sertoli cells at 1000-fold lower concentrations (10(-7) M) than the peptides Ac-TRDL-NH2, Ac-SRAY-NH2, or Ac-TDSDS-NH2. In another peptide, Ac-TDSDS-NH-(CH2)5-CO-SRAY-NH-(CH2)4-CO-TRDL-NH2, all three binding regions have been linked. This peptide appeared to be a strong agonist of FSH action, as measured by the ability to stimulate cAMP production, at concentrations

  18. Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer

    SciTech Connect

    Berthelsen, J.G.

    1984-02-01

    Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray (Gy)) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.

  19. Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein.

    PubMed Central

    Murphy, J R; Bishai, W; Borowski, M; Miyanohara, A; Boyd, J; Nagle, S

    1986-01-01

    The structural gene for diphtheria toxin, tox, has been modified at its Sph I site by the introduction of an oligonucleotide linker encoding a unique Pst I restriction endonuclease site and a synthetic oligonucleotide encoding alpha-melanocyte-stimulating hormone (alpha-MSH). The resulting fusion gene directs the expression of a diphtheria toxin-related alpha-MSH hybrid protein in which the diphtheria toxin receptor-binding domain has been replaced with alpha-MSH sequences. The chimeric toxin has been partially purified from periplasmic extracts of recombinant Escherichia coli K-12 and has been found to be selectively toxic for alpha-MSH receptor-positive human malignant melanoma NEL-M1 cells in vitro. Images PMID:3095831

  20. 2012 European Thyroid Association Guidelines for the Management of Familial and Persistent Sporadic Non-Autoimmune Hyperthyroidism Caused by Thyroid-Stimulating Hormone Receptor Germline Mutations

    PubMed Central

    Paschke, R.; Niedziela, M.; Vaidya, B.; Persani, L.; Rapoport, B.; Leclere, J.

    2012-01-01

    All cases of familial thyrotoxicosis with absence of evidence of autoimmunity and all children with persistent isolated neonatal hyperthyroidism should be evaluated for familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) or persistent sporadic non-autoimmune hyperthyroidism (PSNAH). First, all index patients should be analysed for the presence/absence of a thyroid-stimulating hormone (TSH) receptor (TSHR) germline mutation, and if they display a TSHR germline mutation, all other family members including asymptomatic and euthyroid family members should also be analysed. A functional characterization of all new TSHR mutations is necessary. Appropriate ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences, especially in children. Therefore, in children the diagnosis of FNAH or PSNAH needs to be established as early as possible in the presence of the clinical hallmarks of the disease. PMID:24783013

  1. 2012 European thyroid association guidelines for the management of familial and persistent sporadic non-autoimmune hyperthyroidism caused by thyroid-stimulating hormone receptor germline mutations.

    PubMed

    Paschke, R; Niedziela, M; Vaidya, B; Persani, L; Rapoport, B; Leclere, J

    2012-10-01

    All cases of familial thyrotoxicosis with absence of evidence of autoimmunity and all children with persistent isolated neonatal hyperthyroidism should be evaluated for familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) or persistent sporadic non-autoimmune hyperthyroidism (PSNAH). First, all index patients should be analysed for the presence/absence of a thyroid-stimulating hormone (TSH) receptor (TSHR) germline mutation, and if they display a TSHR germline mutation, all other family members including asymptomatic and euthyroid family members should also be analysed. A functional characterization of all new TSHR mutations is necessary. Appropriate ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences, especially in children. Therefore, in children the diagnosis of FNAH or PSNAH needs to be established as early as possible in the presence of the clinical hallmarks of the disease. PMID:24783013

  2. Use of Follicular Output Rate to Predict Intracytoplasmic Sperm Injection Outcome

    PubMed Central

    Rehman, Rehana; Mustafa, Rozina; Baig, Mukhtiar; Arif, Sara; Hashmi, Muhammad Faisal

    2016-01-01

    Background The measurement of follicular output rate (FORT) has been proposed as a good indicator for evaluating follicular response to the exogenous recombinant folliclestimulating hormone (rFSH). This places FORT as a promising qualitative marker for ovarian function. The objective of the study was to determine FORT as a predictor of oocyte competence, embryo quality and clinical pregnancy after intracytoplasmic sperm injection (ICSI). Materials and Methods This prospective study was carried out on a group of infer- tile females (n=282) at Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2010 till August 2013. Downregulated females were stimulated in injection gonadotropins and on ovulation induction day, pre-ovulatory follicle count (PFC) was determined using transvaginal ultrasound scan (TVUS), and FORT was determined as a ratio of PFC to antral follicle count (AFC)×100. Group I consisted of females with a negative pregnancy test, while group II had a positive pregnancy test that was confirmed with the appearance of fetal cardiac activity. Linear regression analyses of categorical variables of clinical pregnancy along with other independent variables, including FORT, were performed using SPSS version 15.0. Results Pregnancy occurred in 101/282 women who were tested, recording a clinical pregnancy rate of about 35.8%. FORT values were higher in group II as compared to group I females (P=0.0001). In multiple regression analysis, 97.7, 87.1, 78.2, and 83.4% variations were explained based on the number of retrieved oocytes per patients, number of metaphase II oocytes retrieved, number of fertilized oocytes, and number of cleaved embryos, respectively, indicating FORT as an independent predictor. Conclusion FORT is a predictor of oocyte competence in terms of a number of retrieved, mature and fertilized oocytes. It also gives information about the number of cleaved embryos and clinical pregnancy rate. PMID:27441049

  3. The direct cooling of the preoptic-hypothalamic area elicits the release of thyroid stimulating hormone during wakefulness but not during REM sleep.

    PubMed

    Martelli, Davide; Luppi, Marco; Cerri, Matteo; Tupone, Domenico; Mastrotto, Marco; Perez, Emanuele; Zamboni, Giovanni; Amici, Roberto

    2014-01-01

    Thermoregulatory responses to temperature changes are not operant during REM sleep (REMS), but fully operant in non-REM sleep and wakefulness. The specificity of the relationship between REMS and the impairment of thermoregulation was tested by eliciting the reflex release of Thyrotropin Releasing Hormone (TRH), which is integrated at hypothalamic level. By inducing the sequential secretion of Thyroid Stimulating Hormone (TSH) and Thyroid Hormone, TRH intervenes in the regulation of obligatory and non-shivering thermogenesis. Experiments were performed on male albino rats implanted with epidural electrodes for EEG recording and 2 silver-copper wire thermodes, bilaterally placed in the preoptic-hypothalamic area (POA) and connected to small thermoelectric heat pumps driven by a low-voltage high current DC power supply. In preliminary experiments, a thermistor was added in order to measure hypothalamic temperature. The activation of TRH hypophysiotropic neurons by the thermode cooling of POA was indirectly assessed, in conditions in which thermoregulation was either fully operant (wakefulness) or not operant (REMS), by a radioimmunoassay determination of plasmatic levels of TSH. Different POA cooling were performed for 120 s or 40 s at current intensities of 80 mA and 125 mA, respectively. At both current intensities, POA cooling elicited, with respect to control values (no cooling current), a significant increase in plasmatic TSH levels in wakefulness, but not during REMS. These results confirm the inactivation of POA thermal sensitivity during REMS and show, for the first time, that this inactivation concerns also the fundamental endocrine control of non-shivering thermogenesis. PMID:24498374

  4. The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine

    PubMed Central

    Xu, Cheng; Li, Ying-Chun; Yang, Hua; Long, Yan; Chen, Min-Jian; Qin, Yu-Feng; Xia, Yan-Kai; Song, Ling; Gu, Ai-Hua; Wang, Xin-Ru

    2014-01-01

    Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star™ (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels. PMID:24713829

  5. The preparation and application of N-terminal 57 amino acid protein of the follicle-stimulating hormone receptor as a candidate male contraceptive vaccine.

    PubMed

    Xu, Cheng; Li, Ying-Chun; Yang, Hua; Long, Yan; Chen, Min-Jian; Qin, Yu-Feng; Xia, Yan-Kai; Song, Ling; Gu, Ai-Hua; Wang, Xin-Ru

    2014-01-01

    Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star TM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels. PMID:24713829

  6. Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

    PubMed Central

    Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

    2015-01-01

    This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755

  7. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    SciTech Connect

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  8. Haplotype Structure of FSHB, the Beta-Subunit Gene for Fertility-Associated Follicle-Stimulating Hormone: Possible Influence of Balancing Selection

    PubMed Central

    Grigorova, M; Rull, K; Laan, M

    2007-01-01

    Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments. PMID:17227474

  9. Re-introduction and evaluation of an accurate, high capacity bioassay for melanocyte-stimulating hormone using the skin of Anolis carolinensis in vitro.

    PubMed

    Tilders, F J; van Delft, A M; Smelik, P G

    1975-08-01

    A simple and rapid assay for the quantitative determination of melanocyte-stimulating hormone (MSH) activity, using skin fragments of the lizard Anolis carolinensis in vitro, is described in detail. This assay, in which a quantal response (e.g. induction of a brownish-green colour) can be detected by visual observation, allows determination of MSH activity in up to 50 samples/day by one person, using the skin of one lizard. The mean dose found to induce this colour change was 0-15 ng synthetic alpha-MSH/ml (range 0-02-0-5 ng/ml). The assays shows high accuracy, reproducibility and specificity. Anterior and posterior lobe hormones as well as pituitary catecholamines do not interfere with the determination of pituitary MSH activitymthe method is compared with the assay using hypophysectomized frogs (Rana pipiens) in vivo. Determinations of MSH in pituitary extracts by both methods gave quantitatively similar results when determined with alpha-MSH as the reference substance. However, when beta-seryl MSH was used as a reference, the two assays gave different results for the MSH activity of the pituitary extractsmthis indicates that MSH from the rat pituitary gland has a biological activity similar to that of alpha-MSH rather than to that of beta-seryl MSH. PMID:170354

  10. Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

    PubMed

    Ghizzoni, L; Virdis, R; Ziveri, M; Lamborghini, A; Alberini, A; Volta, C; Bernasconi, S

    1989-10-01

    To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche. PMID:2550509

  11. Selection of Suitable Reference Genes for RT-qPCR Normalization under Abiotic Stresses and Hormone Stimulation in Persimmon (Diospyros kaki Thunb)

    PubMed Central

    Wang, Peihong; Xiong, Aisheng; Gao, Zhihong; Yu, Xinyi; Li, Man; Hou, Yingjun; Sun, Chao; Qu, Shenchun

    2016-01-01

    The success of quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to quantify gene expression depends on the stability of the reference genes used for data normalization. To date, systematic screening for reference genes in persimmon (Diospyros kaki Thunb) has never been reported. In this study, 13 candidate reference genes were cloned from 'Nantongxiaofangshi' using information available in the transcriptome database. Their expression stability was assessed by geNorm and NormFinder algorithms under abiotic stress and hormone stimulation. Our results showed that the most suitable reference genes across all samples were UBC and GAPDH, and not the commonly used persimmon reference gene ACT. In addition, UBC combined with RPII or TUA were found to be appropriate for the "abiotic stress" group and α-TUB combined with PP2A were found to be appropriate for the "hormone stimuli" group. For further validation, the transcript level of the DkDREB2C homologue under heat stress was studied with the selected genes (CYP, GAPDH, TUA, UBC, α-TUB, and EF1-α). The results suggested that it is necessary to choose appropriate reference genes according to the test materials or experimental conditions. Our study will be useful for future studies on gene expression in persimmon. PMID:27513755

  12. Selection of Suitable Reference Genes for RT-qPCR Normalization under Abiotic Stresses and Hormone Stimulation in Persimmon (Diospyros kaki Thunb).

    PubMed

    Wang, Peihong; Xiong, Aisheng; Gao, Zhihong; Yu, Xinyi; Li, Man; Hou, Yingjun; Sun, Chao; Qu, Shenchun

    2016-01-01

    The success of quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to quantify gene expression depends on the stability of the reference genes used for data normalization. To date, systematic screening for reference genes in persimmon (Diospyros kaki Thunb) has never been reported. In this study, 13 candidate reference genes were cloned from 'Nantongxiaofangshi' using information available in the transcriptome database. Their expression stability was assessed by geNorm and NormFinder algorithms under abiotic stress and hormone stimulation. Our results showed that the most suitable reference genes across all samples were UBC and GAPDH, and not the commonly used persimmon reference gene ACT. In addition, UBC combined with RPII or TUA were found to be appropriate for the "abiotic stress" group and α-TUB combined with PP2A were found to be appropriate for the "hormone stimuli" group. For further validation, the transcript level of the DkDREB2C homologue under heat stress was studied with the selected genes (CYP, GAPDH, TUA, UBC, α-TUB, and EF1-α). The results suggested that it is necessary to choose appropriate reference genes according to the test materials or experimental conditions. Our study will be useful for future studies on gene expression in persimmon. PMID:27513755

  13. Differentiation-specific alterations to glutathione synthesis in and hormonally stimulated release from human skeletal muscle cells.

    PubMed

    Cotgreave, Ian A; Goldschmidt, Lina; Tonkonogi, Michail; Svensson, Michael

    2002-03-01

    Muscle atrophy and cachexia are associated with many human diseases. These catabolic states are often associated with the loss of glutathione (GSH), which is thought to contribute to the induction of oxidative stress within the muscle. Glutathione synthesis and secretary characteristics were studied in human skeletal muscle myoblasts and myotube-like cells derived from the myoblasts by growth factor restriction. Differentiation was associated with a shift in the sulfur amino acid precursor specificity for synthesis of GSH from cystine to cysteine, as well as loss in ability to use extracellular glutathione and activation of methionine use. The thiol drug N-acetylcysteine was also shown to be an effective precursor irrespective of the state of differentiation. Additionally, myoblasts and myotube cultures were shown to secrete GSH continually, but only the differentiated cells responded to stress hormones such as glucagon, vasopressin, and phenylephrine, by increased secretion of the tripeptide. The data suggest that the skeletal muscle cells may provide an important hormonally regulated extra-hepatic source of systemic GSH and also shed light on the mechanisms of accelerated turnover of GSH operating during strenuous muscle activity and trauma. The data may also provide biochemical rationales for the nutritional and/or pharmacological manipulation of GSH with sulfur amino acid precursors during the treatment of muscle-specific oxidative stress and atrophy. PMID:11821257

  14. Genistein selectively inhibits estrogen-induced cell proliferation and other responses to hormone stimulation in the prepubertal rat uterus.

    PubMed

    Gaete, Leonardo; Tchernitchin, Andrei N; Bustamante, Rodrigo; Villena, Joan; Lemus, Igor; Gidekel, Manuel; Cabrera, Gustavo; Carrillo, Omar

    2011-12-01

    Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17β (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women. PMID:21612459

  15. Structure–Activity Relationships of Cyclic Lactam Analogues of α-Melanocyte-Stimulating Hormone (α-MSH) Targeting the Human Melanocortin-3 Receptor

    PubMed Central

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Dedek, Matthew M.; Cain, James P.; Van Scoy, April R.; Tan, Bahar; Vagner, Josef; Trivedi, Dev; Hruby, Victor J.

    2008-01-01

    A variety of dicarboxylic acid linkers introduced between the α-amino group of Pro6 and the ε-amino group of Lys10 of the cyclic lactam α-melanocyte-stimulating hormone (α-MSH)-derived Pro6-D-Phe7/D-Nal(2′)7-Arg8-Trp9-Lys10-NH2 pentapeptide template lead to nanomolar range and selective hMC3R agonists and antagonists. Replacement of the Pro6 residue and the dicarboxylic acid linker with 2,3-pyrazine-dicarboxylic acid furnished a highly selective nanomolar range hMC3R partial agonist (analogue 12, c[CO-2,3-pyrazine-CO-D-Phe-Arg-Trp-Lys]-NH2, EC50 = 27 nM, 70% max cAMP) and an hMC3R antagonist (analogue 13, c[CO-2,3-pyrazine-CO-D-Nal(2′)-Arg-Trp-Lys]-NH2, IC50 = 23 nM). Modeling experiments suggest that 2,3-pyrazinedicarboxylic acid stabilizes a β-turn-like structure with the D-Phe/D-Nal(2′) residues, which explains the high potency of the corresponding peptides. Placement of a Nle residue in position 6 produced a hMC3R/hMC5R antagonist (analogue 15, c[CO-(CH2)2-CO-Nle-D-Nal(2′)-Arg-Trp-Lys]-NH2, IC50 = 12 and 17 nM, respectively), similarly to the previously described cyclic γ-melanocyte-stimulating hormone (γ-MSH)-derived hMC3R/hMC5R antagonists. These newly developed melanotropins will serve as critical biochemical tools for elucidating the full spectrum of functions performed by the physiologically important melanocortin-3 receptor. PMID:18088090

  16. LPXRFamide peptide stimulates growth hormone and prolactin gene expression during the spawning period in the grass puffer, a semi-lunar synchronized spawner.

    PubMed

    Shahjahan, Md; Doi, Hiroyuki; Ando, Hironori

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) plays as a multifunctional neurohormone that controls reproduction in birds and mammals. LPXRFamide (LPXRFa) peptide, the fish ortholog of GnIH, has been shown to regulate the secretion of not only gonadotropin (GTH) but also growth hormone (GH) and prolactin (PRL), which are potentially important for gonadal function. To investigate the role of LPXRFa peptide on reproduction of the grass puffer, which spawns in semilunar cycles, we examined changes in the levels of gh and prl expression over the several months during the reproductive cycle, and the effects of goldfish LPXRFa peptide-1 (gfLPXRFa-1) on their expression were examined using primary pituitary cultures. The expression levels of both gh and prl showed significant changes during the reproductive cycle in both sexes with one peak in the spawning and pre-spawning periods for gh and prl, respectively. Particularly, gh showed substantial increase in expression in the spawning and post-spawning periods, indicative of its essentiality in the advanced stage of reproduction. gfLPXRFa-1 stimulated the expression of both gh and prl but there was a marked difference in response between them: gfLPXRFa-1 stimulated gh expression at a relatively low dose but little effect was observed on prl. Combined with the previous results of daily and circadian oscillations of lpxrfa expression, the present results suggest that LPXRFa peptide is important in the control of the cyclic reproduction by serving as a multifunctional hypophysiotropic factor that regulates the expression of gh and prl as well as GTH subunit genes. PMID:26385315

  17. Luteinizing hormone (LH) blood test

    MedlinePlus

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  18. Effects of Anesthetic Agent Propofol on Postoperative Sex Hormone Levels

    PubMed Central

    Kim, H.; Ku, S.-Y.; Kim, H. C.; Suh, C. S.; Kim, S. H.; Choi, Y. M.

    2016-01-01

    Introduction: Several studies have found anesthetic agents including propofol in ovarian follicular fluid. However, little is known about the effect of anesthetic agents on ovarian function. We aimed to investigate whether there were differences in the postoperative levels of sex hormones when propofol was used as the anesthetic agent. Methods: A retrospective review was done of 80 patients who underwent ovarian surgery, with 72 infertile women serving as controls. Patients were included in the study if their serum estradiol (E2) and follicle stimulating hormone (FSH) levels were measured during their first postoperative menstrual cycle. Results: Patients were grouped according to the use or non-use of propofol as follows: propofol group (n = 39) and non-propofol group (n = 41). The control group did not undergo surgery. Postoperative E2 levels did not differ between the three groups, but FSH levels were significantly higher in the patients who had undergone surgery compared to controls (p < 0.05). Post-hoc analysis of E2 and FSH levels in the propofol and non-propofol groups did not show any significant differences. Conclusions: The use of propofol did not result in any differences compared to other anesthetic agents in terms of postoperative sex hormone levels after gynecologic surgery. The type of anesthetic agent does not seem to affect the postoperative levels of female sex hormones. PMID:27134297

  19. Origin of bovine follicular fluid and its effect during in vitro maturation on the developmental competence of bovine oocytes.

    PubMed

    Ali, Atef; Coenen, Karine; Bousquet, Daniel; Sirard, Marc-André

    2004-12-01

    Protein supplementation during in vitro maturation can profoundly affect both the rate and overall efficiency of the maturation procedure. The present study was conducted to assess the ability of different concentrations (1, 5, and 10%) of bovine follicular fluid (bFF) to support in vitro maturation of oocytes and subsequent developmental capacity. The bFF was derived either from competent follicles ( > 8 mm) obtained by transvaginal recovery following superovulation or from a pool of small follicles (2-5 mm) from abbatoir-derived ovaries. Bovine oocytes were cultured for 24 h in synthetic oviduct fluid medium (m-SOF) supplemented with polyvinylpyrrolidone. Following fertilization and embryo culture, more oocytes (P < 0.05) reached the blastocyst stage when oocytes were cultured with 5% bFF from competent follicles (41 +/- 3.7%) compared with bFF derived from small follicles (16 +/- 2.9%). Estradiol and recombinant human follicle stimulating hormone added to the competent bFF during maturation acted in synergy to increase blastocyst production rate (P < 0.05); this blastocyst production rate (57 +/- 1.2%) was higher than those obtained with the addition of these two hormones to bFF derived from small follicles (26 +/- 2.9%). The quality of blastocysts obtained was reflected by inner cell mass (51.30 +/- 3.5 and 25.50 +/- 3.7) and trophectoderm cell numbers (99.72 +/- 2.5 and 94.80 +/- 4.7) for bFF from competent and small follicles, respectively. In conclusion, follicular fluid originating from competent follicles increased the developmental competence of abbatoir-derived oocytes. PMID:15511547

  20. Follicular lymphoma presenting with hypercalcaemia: an unusual mechanism of hypercalcaemia.

    PubMed

    Martens, P; Addissie, B; Kumar, R

    2015-06-01

    Hypercalcaemia is a frequent finding in patients with cancer. In up to 30% of malignancies, the disease course is complicated with hypercalcaemia. For hospitalized patients, cancer is the most common cause of hypercalcaemia. In normal physiological circumstances, the ionized calcium is kept in check by the influence of two important hormones, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D). However, cancer can misbalance the calcium homeostasis by generating certain humoural mediators. Overproduction of parathyroid hormone-related peptide (PTH-rp), intact PTH, 1,25(OH)2D, and cytokines all cause hypercalcaemia. Hypercalcaemia is frequent in certain haematological cancers such as multiple myeloma and aggressive lymphomas. But hypercalcaemia is rare in patients with indolent lymphomas such follicular lymphoma. This case illustrates as a first to our knowledge the involvement of cytokines and chemokines in the pathophysiology of lymphoma-related hypercalcaemia. A pathophysiological mechanism is offered based upon the current understanding of cytokines and chemokines related to follicular lymphoma. PMID:25475431

  1. Osmotic and hormonal stimulation of the third ventricular region of ducks: antidiuretic, circulatory and local neuronal responses.

    PubMed

    Simon-Oppermann, C; Kanosue, K; Günther, O; Schmid, H

    1989-01-01

    By means of local microperfusion of the 3rd cerebral ventricle, antidiuretic and circulatory responses to stimulations with various hypertonic solutions and norepinephrine were analyzed in conscious ducks. The results suggest ionic rather than osmometric responsiveness of periventricular osmoreceptive elements, which is in line with single unit recordings of periventricular neurons tested in vitro for their osmoresponsiveness. These neurons were located subependymally at the site of greatest responsiveness in vivo, and corresponded to morphologically identified neurons projecting to the neuroendocrine hypothalamo-pituitary system. Antidiuresis was combined with increases in arterial pressure and heart rate in response to hypertonic stimulations with monovalent cations; divalent cations produced long-lasting antidiuresis and equivocal circulatory responses. Norepinephrine elicited antidiuresis which was accompanied by arterial hypotension and bradycardia. Osmotically and norepinephrine induced antidiuresis was combined with increases of plasma ADH concentration. Different modulatory actions of intrinsic adrenergic, angiotensinergic and vasotocinergic neurons are suggested in hypothalamic control of autonomic functions. PMID:2554682

  2. Prolonged stimulation of corticosterone secretion by corticotropin-releasing hormone in rats exhibiting high preference for dietary fat

    USGS Publications Warehouse

    Herminghuysen, D.; Plaisance, K.; Pace, R. M., III; Prasad, C.

    1998-01-01

    Through the secretion of corticosterone, the hypothalamo-pituitary-adrenal (HPA) axis is thought to play an important role in the regulation of caloric intake and dietary fat preference. In an earlier study, we demonstrated a positive correlation between urinary corticosterone output and dietary fat preference. Furthermore, dietary fat preference was augmented following chronic but not acute hypercorticosteronemia produced by exogenous corticosterone administration. These observations led us to explore whether the HPA axis of rats exhibiting high preference for fat may have exaggerated sensitivity to corticotropin-releasing hormone (CRH). The results of these studies show a delayed and blunted but more prolonged corticosterone response to CRH in the fat-preferring rats compared with that of the carbohydrate-preferring rats.

  3. Trial of Recombinant Follicle-Stimulating Hormone Pretreatment for GnRH-Induced Fertility in Patients with Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Hayes, Frances J.; Boepple, Paul A.; Lee, Hang; Loughlin, Kevin R.; Dym, Martin; Sluss, Patrick M.; Crowley, William F.

    2013-01-01

    Context and Objective: The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method. Design and Setting: This was a randomized, open-label treatment protocol at an academic medical center. Patients and Interventions: GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses. Results: rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts. Conclusions: rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles. PMID:24037890

  4. Profiles of alpha-melanocyte-stimulating hormone in the Japanese flounder as revealed by a newly developed time-resolved fluoroimmunoassay and immunohistochemistry.

    PubMed

    Amiya, Noriko; Amano, Masafumi; Takahashi, Akiyoshi; Yamanome, Takeshi; Yamamori, Kunio

    2007-03-01

    Profiles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the Japanese flounder were examined by a newly developed time-resolved fluoroimmunoassay (TR-FIA) and immunohistochemistry. A TR-FIA for alpha-MSH was newly developed, and its levels in the pituitary gland and plasma of Japanese flounder reared in a white or black tank for 5 months were compared. A competitive assay using two antibodies was performed among secondary antibodies in the solid phase, alpha-MSH antibodies, samples, and europium-labeled Des-Ac-alpha-MSH. The sensitivity of the assay, defined as twice the standard deviation at a zero dose, was 0.98 ng/ml (49 pg/well). The intra- and interassay coefficients of variation of the assay were 8.8% (n=8) and 17.3% (n=5), respectively, at about 50% binding. Cross-reactivities of Des-Ac-alpha-MSH and Di-Ac-alpha-MSH were about 100%. Cross-reactivities of adrenocorticotropic hormone, salmon gonadotropin-releasing hormone (sGnRH), and chicken GnRH-II were less than 0.2%, and that of melanin-concentrating hormone was less than 2.0% at 50% binding. Displacement curves of serially twofold-diluted hypothalamus extract, pituitary gland extract, and plasma extract of Japanese flounder with the assay buffer were parallel to the alpha-MSH standard curve. Moreover, displacement curves of serially twofold-diluted hypothalamus and/or pituitary gland extract of masu salmon, goldfish, red seabream, Japanese eel, tiger puffer, and barfin flounder with the assay buffer were also parallel to the alpha-MSH standard. In Japanese flounder, total immunoreactive (ir)-alpha-MSH levels in the pituitary gland were lower in the black tank, whereas those in the plasma tended to be higher in the black tank, suggesting that the synthesis and release of alpha-MSH are higher in the black tank. alpha-MSH-ir cells were detected in the pars intermedia and a small part of the pars distalis of the pituitary gland. alpha-MSH-ir cell bodies were located in the basal hypothalamus and alpha

  5. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I

    PubMed Central

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-01-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition. [BMB Reports 2015; 48(9): 501-506] PMID:25644636

  6. Gankyrin facilitates follicle-stimulating hormone-driven ovarian cancer cell proliferation through the PI3K/AKT/HIF-1α/cyclin D1 pathway.

    PubMed

    Chen, J; Bai, M; Ning, C; Xie, B; Zhang, J; Liao, H; Xiong, J; Tao, X; Yan, D; Xi, X; Chen, X; Yu, Y; Bast, R C; Zhang, Z; Feng, Y; Zheng, W

    2016-05-12

    Gankyrin is a regulatory subunit of the 26kD proteasome complex. As a novel oncoprotein, gankyrin is expressed aberrantly in cancers from several different sites and has been shown to contribute to oncogenesis in endometrial and cervical carcinomas. Neither gankyrin's contribution to the development of epithelial ovarian cancer nor its interaction with follicle-stimulating hormone (FSH)-driven proliferation in ovarian cancer has been studied. Here we have found that gankyrin is overexpressed in ovarian cancers compared with benign ovarian cystadenomas and that gankyrin regulates FSH upregulation of cyclin D1. Importantly, gankyrin regulates PI3K/AKT signaling by downregulating PTEN. Prolonged AKT activation by FSH stimulation of the FSH receptor (FSHR) promotes gankyrin expression, which, in turn, enhances AKT activation by inhibiting PTEN. Overexpression of gankyrin decreases hypoxia inducible factor-1α (HIF-1α) protein levels, but has little effect on HIF-1α mRNA levels, which could be attributed to gankyrin mediating HIF-1α protein stability via the ubiquitin-proteasome pathway. Reduction in HIF-1α protein stability led to attenuation of the binding with cyclin D1 promoter, resulted in abolishment of the negative regulation of cyclin D1 by HIF-1α, which promotes proliferation of ovarian cancer cells. Our results document that gankyrin regulates HIF-1α protein stability and cyclin D1 expression, ultimately mediating FSH-driven ovarian cancer cell proliferation. PMID:26364616

  7. Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells.

    PubMed Central

    Kurebayashi, J.; Sonoo, H.

    1997-01-01

    We recently established a human breast cancer cell line, KPL-3C, from a breast cancer patient with humoral hypercalcaemia. This cell line possesses oestrogen receptor (ER) and secretes parathyroid hormone-related protein (PTHrP) into medium. To investigate the effects of oestrogen and antioestrogens on PTHrP secretion, KPL-3C cells were cultured for 48 h in an oestrogen-eliminated medium with 17beta-oestradiol (E2), tamoxifen (TAM) and/or a pure antioestrogen, ICI182,780 (ICI), and PTHrP secretion was measured using an immunoradiometric assay. The effects of these agents on cell cycle progression were also studied using flow cytometry. E2 (1-100 nM) significantly inhibited PTHrP secretion, whereas both TAM (0.1-10 microM) and ICI (1-100 nM) significantly stimulated it. These effects were completely blocked by the simultaneous addition of 1 nM E2 to the medium. At the same time, E2 significantly increased the percentage of cells during the S and G2/M phases, whereas both antioestrogens significantly increased the percentage of cells during the G0/G1 phase. Again, these cytostatic effects were completely reversed by the addition of E2. These findings indicate that antioestrogens inhibit the growth of ER-positive breast cancer cells but may stimulate PTHrP secretion and that these effects may be mediated by ER. PMID:9192988

  8. Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines.

    PubMed

    Whiteside, Eliza J; Seim, Inge; Pauli, Jana P; O'Keeffe, Angela J; Thomas, Patrick B; Carter, Shea L; Walpole, Carina M; Fung, Jenny N T; Josh, Peter; Herington, Adrian C; Chopin, Lisa K

    2013-08-01

    The molecular mechanisms involved in non‑small cell lung cancer tumourigenesis are largely unknown; however, recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a role. In this study, we used public databases to identify an mRNA-like, candidate long non-coding RNA, GHSROS (GHSR opposite strand), transcribed from the antisense strand of the ghrelin receptor gene, growth hormone secretagogue receptor (GHSR). Quantitative real-time RT-PCR revealed higher expression of GHSROS in lung cancer tissue compared to adjacent, non-tumour lung tissue. In common with many long non-coding RNAs, GHSROS is 5' capped and 3' polyadenylated (mRNA-like), lacks an extensive open reading frame and harbours a transposable element. Engineered overexpression of GHSROS stimulated cell migration in the A549 and NCI-H1299 non-small cell lung cancer cell lines, but suppressed cell migration in the Beas-2B normal lung-derived bronchoepithelial cell line. This suggests that GHSROS function may be dependent on the oncogenic context. The identification of GHSROS, which is expressed in lung cancer and stimulates cell migration in lung cancer cell lines, contributes to the growing number of non-coding RNAs that play a role in the regulation of tumourigenesis and metastatic cancer progression. PMID:23722988

  9. α-Melanocyte-stimulating hormone prevents glutamate excitotoxicity in developing chicken retina via MC4R-mediated down-regulation of microRNA-194

    PubMed Central

    Zhang, Yan; Bo, Qiyu; Wu, Weihui; Xu, Chang; Yu, Guangwei; Ma, Shan; Yang, Qianhui; Cao, Yunshan; Han, Qian; Ru, Yusha; Liu, Xun; Hua Wei, Rui; Wang, Fei E.; Zhang, Xiaomin; Li, Xiaorong

    2015-01-01

    Glutamate excitotoxicity is a common pathology to blinding ischemic retinopathies, such as diabetic retinopathy, glaucoma, and central retinal vein or artery occlusion. The development of an effective interventional modality to glutamate excitotoxicity is hence important to preventing blindness. Herein we showed that α-melanocyte-stimulating hormone (α-MSH) time-dependently protected against glutamate-induced cell death and tissue damage in an improved embryonic chicken retinal explant culture system. α-MSH down-regulated microRNA-194 (miR-194) expression during the glutamate excitotoxicity in the retinal explants. Furthermore, pharmacological antagonists to melanocortin 4 receptor (MC4R) and lentivirus-mediated overexpression of pre-miR-194 abrogated the suppressing effects of α-MSH on glutamate-induced activities of caspase 3 or 7, the ultimate enzymes for glutamate-induced cell death. These results suggest that the protective effects of α-MSH may be due to the MC4R mediated-down-regulation of miR-194 during the glutamate-induced excitotoxicity. Finally, α-MSH attenuated cell death and recovered visual functions in glutamate-stimulated post-hatch chick retinas. These results demonstrate the previously undescribed protective effects of α-MSH against glutamate-induced excitotoxic cell death in the cone-dominated retina both in vitro and in vivo, and indicate a novel molecular mechanism linking MC4R-mediated signaling to miR-194. PMID:26507936

  10. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

    PubMed

    Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

    2015-09-01

    Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition. PMID:25644636

  11. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    PubMed Central

    Karimi Jashni, Hojatollah; Kargar Jahromi, Hossein; Ghorbani Ranjbary, Ali; Kargar Jahromi, Zahra; Khabbaz Kherameh, Zahra

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw) of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH), follicular stimulating hormone (FSH), Luteinal hormone (LH), estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05). Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats. PMID:27200420

  12. Nitric oxide enhances the sensitivity of alpaca melanocytes to respond to {alpha}-melanocyte-stimulating hormone by up-regulating melanocortin-1 receptor

    SciTech Connect

    Dong, Yanjun; Cao, Jing; Wang, Haidong; Zhang, Jie; Zhu, Zhiwei; Bai, Rui; Hao, HuanQing; He, Xiaoyan; Fan, Ruiwen; Dong, Changsheng

    2010-06-11

    Nitric oxide (NO) and {alpha}-melanocyte-stimulating hormone ({alpha}-MSH) have been correlated with the synthesis of melanin. The NO-dependent signaling of cellular response to activate the hypothalamopituitary proopiomelanocortin system, thereby enhances the hypophysial secretion of {alpha}-MSH to stimulate {alpha}-MSH-receptor responsive cells. In this study we investigated whether an NO-induced pathway can enhance the ability of the melanocyte to respond to {alpha}-MSH on melanogenesis in alpaca skin melanocytes in vitro. It is important for us to know how to enhance the coat color of alpaca. We set up three groups for experiments using the third passage number of alpaca melanocytes: the control cultures were allowed a total of 5 days growth; the UV group cultures like the control group but the melanocytes were then irradiated everyday (once) with 312 mJ/cm{sup 2} of UVB; the UV + L-NAME group is the same as group UV but has the addition of 300 {mu}M L-NAME (every 6 h). To determine the inhibited effect of NO produce, NO produces were measured. To determine the effect of the NO to the key protein and gene of {alpha}-MSH pathway on melanogenesis, the key gene and protein of the {alpha}-MSH pathway were measured by quantitative real-time PCR and Western immunoblotting. The results provide exciting new evidence that NO can enhance {alpha}-MSH pathway in alpaca skin melanocytes by elevated MC1R. And we suggest that the NO pathway may more rapidly cause the synthesis of melanin in alpaca skin under UV, which at that time elevates the expression of MC1R and stimulates the keratinocytes to secrete {alpha}-MSH to enhance the {alpha}-MSH pathway on melanogenesis. This process will be of considerable interest in future studies.

  13. Sialadenitis following low dose I-131 diagnostic thyroid scan with Thyrogen® (recombinant human thyroid stimulating hormone - thyrotropin alfa)

    PubMed Central

    Gonzalez, Marta E; Muttikkal, Thomas Jose Eluvathingal; Rehm, Patrice K

    2015-01-01

    Salivary dysfunction and sialadenitis are well known complications of radioiodine treatment for thyroid cancer. The parotid gland is more frequently affected and the salivary gland injury is dose related. The symptoms may develop shortly after therapeutic Iodine 131(I-131) administration or months later and progress with time. The development of unilateral parotiditis following a low dose, diagnostic I-131 scan performed following Thyrogen stimulation in a patient without prior history of sialadenitis is rare in our experience, and has not been reported in the medical literature. PMID:26622936

  14. Serum thyroxine concentration before and after administration of thyrotropin-stimulating hormone decreases with chronological age in the dog

    SciTech Connect

    Weller, R.E.; Park, J.F.; Kinnas, T.C.; Stevens, D.L.

    1983-06-01

    Thyroid function in the dog was evaluated as a function of increasing chronological age. Ninety-one dogs between the ages of 14.6 and 160.8 months were evaluated. Basal serum triiodothyronine (T/sub 3/) concentration, basal serum thyroxine (T/sub 4/) and serum T/sub 4/ concentration following stimulation by thyrotropin were found to decrease with age. The results suggested that age may be an important factor in interpreting thyroid profiles in the dog. 17 refs., 4 figs., 1 tab.

  15. Atrial natriuretic factor (ANF) inhibits thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B. )

    1990-01-01

    Recently, thyroid follicular cells were shown to exhibit atrial natriuretic factor (ANF)-like immunoreactivity and high affinity ANF receptors. In this study, we therefore examined the effects of synthetic rat ANF{sub 1-28} on basal and stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Iodine deficient mice were pretreated with {sup 125}I and thyroxine. ANF (3 nmol/animal) was found to inhibit the increase in blood radioiodine levels that was induced by TSH or vasoactive intestinal polypeptide (VIP). Furthermore, ANF and norepinephrine additively inhibited the TSH-induced increase in blood radioiodine levels. It is concluded that ANF inhibits thyroid hormone secretion, which, therefore, might be locally regulated by intrathyroidal ANF.

  16. Primate follicular development and oocyte maturation in vitro

    PubMed Central

    Xu, Jing; Xu, Min; Bernuci, Marcelo P; Fisher, Thomas E; Shea, Lonnie D; Woodruff, Teresa K; Zelinski, Mary B; Stouffer, Richard L

    2014-01-01

    The factors and processes involved in primate follicular development are complex and not fully understood. An encapsulated three-dimensional (3D) follicle culture system could be a valuable in vitro model to study the dynamics and regulation of folliculogenesis in intact individual follicles in primates. Besides the research relevance, in vitro follicle maturation (IFM) is emerging as a promising approach to offer options for fertility preservation in female patients with cancer. This review summarizes the current published data on in vitro follicular development from the preantral to small antral stage in nonhuman primates, including follicle survival and growth, endocrine (ovarian steroid hormone) and paracrine/autocrine (local factor) function, as well as oocyte maturation and fertilization. Future directions include major challenges and strategies to further improve follicular growth and differentiation with oocytes competent for in vitro fertilization and subsequent embryonic development, as well as opportunities to investigate primate folliculogenesis by utilizing this 3D culture system. The information may be valuable in identifying optimal conditions for human follicle culture, with the ultimate goal of translating the experimental results and products to patients, thereby facilitating diagnostic and therapeutic approaches for female fertility. PMID:24097381

  17. Regulation of Anti-Müllerian Hormone and Its Receptor Expression around Follicle Deviation in Cattle.

    PubMed

    Ilha, G F; Rovani, M T; Gasperin, B G; Ferreira, R; de Macedo, M P; Neto, O A; Duggavathi, R; Bordignon, V; Gonçalves, Pbd

    2016-04-01

    The anti-Müllerian hormone (AMH) is an important marker of ovarian reserve and for predicting the response to superovulatory treatments in several species. The objective of this study was to investigate whether AMH and its receptor (AMHR2) are regulated in bovine granulosa cells during follicular development. In the first experiment, granulosa cells were retrieved from the two largest follicles on days 2 (before), 3 (at the expected time) or 4 (after deviation) of follicular wave. In the second experiment, four doses of FSH (30, 30, 20 and 20 mg) or saline were administered twice a day starting on Day 2 of the first follicular wave of the cycle. Granulosa cells and follicular fluid were collected from the two largest follicles 12 h after the last injection of FSH or saline. AMH mRNA abundance was similar in granulosa cells of the two largest follicles (F1 and F2) before deviation (Day 2), but greater in dominant (DF) than subordinate follicles (SF) at the expected time (Day 3) and after (Day 4) deviation (p < 0.05). In experiment 1, AMH mRNA levels declined in both DF and SF near the expected time and after deviation when compared to before deviation. There was no difference in AMHR2 mRNA levels before and during follicular deviation (p > 0.05), but they tended to be greater in DFs than SFs (p < 0.1) after deviation. Experiment 2 showed that AMH and AMHR2 mRNA in granulosa cells and AMH protein abundance in follicular fluid were similar (p > 0.05) between both co-dominant follicles collected from the FSH-treated cows. These findings indicate the followings: AMH mRNA levels decrease in both DFs and SFs during follicular deviation; granulosa cells from heathy follicles express more AMH mRNA compared to subordinate follicles undergoing atresia and FSH stimulates AMH and AMHR2 mRNA expression in granulosa cells of co-dominant follicles. PMID:26815645

  18. Dietary Lipid and Cholesterol Induce Ovarian Dysfunction and Abnormal LH Response to Stimulation in Rabbits

    PubMed Central

    Dupont, Charlotte; Tarrade, Anne; Picone, Olivier; Larcher, Thibaut; Dahirel, Michèle; Poumerol, Elodie; Mandon-Pepin, Béatrice; Lévy, Rachel; Chavatte-Palmer, Pascale

    2013-01-01

    Background/Aim Excess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet) from 10 weeks of age (i.e., 2 weeks before normal onset of puberty) or a control diet (C diet). Methodology/Principal Findings Three experiments were performed, each including 8 treated (HH group) and 8 control (C group) does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH) was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age). In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH) response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR). Conclusion The HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR. PMID:23690983

  19. Immunohistochemical expression of MMP-14 and MMP-2, and MMP-2 activity during human ovarian follicular development

    PubMed Central

    2014-01-01

    Background The aim of this study was to investigate the presence of MMP-14 and MMP-2 during human ovarian follicular development using immunohistochemistry, and the activity of MMP-2 in follicular fluid using zymography. Methods Ovarian tissue collected from the archives of the Department of Pathology was examined and medical records and histopathology were reviewed. Follicular fluids were collected at the IVF-department and analyzed using zymography. Results MMP-14 and MMP-2 were increasingly found in the growing follicles and MMP-2 was highly expressed in the corpus luteum. Pro-MMP-2 was present in follicular fluid of IVF-patients. Conclusions The presence of MMP-14 and MMP-2 during human ovarian follicular development from the primordial follicle to the tertiary follicle and corpus luteum is confirmed, as was indicated by earlier animal studies following stimulation with gonadotrophins. PMID:24485069

  20. Effects of thyroid hormone on Na sup + -K sup + transport in resting and stimulated rat skeletal muscle

    SciTech Connect

    Everts, M.E.; Clausen, T. )

    1988-11-01

    The effects of hypothyroidism and 3,5,3{prime}-triiodothyronine (T{sub 3}) treatment on passive Na{sup +}-K{sup +} fluxes and Na{sup +}-K{sup +} pump concentration were investigated in isolated rat muscle. Within 12 h after a single dose of T{sub 3} (20 {mu}g/100 g body wt), K{sup +} efflux had increased by 21% in soleus and by 20% in extensor digitorum longus muscle. In the presence of ouabain, even larger effects were observed. These changes were associated with a 12% rise in amiloride-suppressible Na{sup +} influx but no significant increase in ({sup 3}H)ouabain binding site concentration. After 3 days of T{sub 3} treatment, the stimulating effect on K{sup +} efflux and Na{