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Sample records for hormonal induced spermiation

  1. Preparation and ultrastructure of spermatozoa from green poison frogs, Dendrobates auratus, following hormonal induced spermiation (Amphibia, Anura, Dendrobatidae).

    PubMed

    Lipke, Christian; Meinecke-Tillmann, Sabine; Meyer, Wilfried; Meinecke, Burkhard

    2009-07-01

    Few ultrastructural studies have been performed on members of the Dendrobatidae, although such investigations can be useful for the understanding of reproductive patterns, as a diagnostic method for males in breeding programs for endangered amphibians and for phylogenetic analysis. The sperm ultrastructure of the Green Poison Frog, Dendrobates auratus, from Panama is described following induced spermiation in living animals. To date only testicular spermatozoa in other dendrobatid frogs have been analysed. Moreover, an electron microscopic preparation method (transmission and scanning electron microscopy) for dendrobatid sperm cells in low concentration is presented. Sperm cells from stimulated frogs (100 IU human chorionic gonadotropin, hCG, twice at an interval of 1h) were recovered via cloaca lavage using 600 microl isotonic phosphate-free amphibian saline (IPS). Centrifuged flushings (5 min, 173 x g) were deposited on microscopic slides. Adherent spermatozoa were treated with Karnovsky fixative (overnight, 4 degrees C). After postfixation (2h, 1% osmium tetroxide), samples were dehydrated in series of ascending acetones (30-100%). For transmission electron microscopy sperm cells were encapsulated using Epon and 1.5% 2,4,6-tris(dimethylaminomethyl)phenol (DMP 30). Ultrathin sections (70 nm) were cut and stained with uranyl acetate (30 min) and lead citrate (5 min). Sperm cells are filiform with a 21.1+/-2.7 microm long and arcuated head and a single tail (35.0+/-4.2 microm length). Their acrosomal complex is located at the anterior portion of the head and consists of the acrosomal vesicle which has low electron density, and the subjacent electron-dense subacrosomal cone. In transverse section, the nucleus is circular (1.9+/-0.2 microm diameter) and conical in longitudinal section. It is surrounded by several groups of mitochondria. The chromatin is highly condensed and electron-dense but shows numerous electron-lucent inclusions. A short midpiece has a

  2. A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus)

    PubMed Central

    2012-01-01

    Background Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Methods Male American toads (Anaxyrus americanus) were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad), human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU), or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. Results The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU), 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms). In addition to having a greater number of responders (P < 0.05), the 300 IU hCG treatment group had a much higher average sperm concentration (P < 0.05) than the treatment group receiving 4.0 micrograms LHRH. In contrast, these two treatments did not result in significant differences in sperm motility or quality of forward progressive motility. However, more males went into amplexus when treated with LHRH vs. hCG (90% vs. 75%) by nine hours post-administration. Conclusion There is a clear

  3. Sperm characteristics and androgens in Acipenser ruthenus after induction of spermiation by carp pituitary extract or GnRHa implants.

    PubMed

    Alavi, Sayyed Mohammad Hadi; Hatef, Azadeh; Mylonas, Constantinos C; Gela, David; Papadaki, Maria; Rodina, Marek; Kašpar, Vojtech; Pšenička, Martin; Podhorec, Peter; Linhart, Otomar

    2012-12-01

    Spermiation and changes in androgen (testosterone, T and 11-ketotestosterone, 11-KT) levels were studied in sterlet (Acipenser ruthenus) treated with GnRH agonist implants (DAla(6)-Pro(9)-LHRHa) at 25 and 75 μg kg(-1) b.w. and compared with those males treated with 4 mg kg(-1) b.w. of carp pituitary extract (CPE) and 3 pellets of Ovopel kg(-1) b.w., which contains DAla(6)-Pro(9)NEt-mGnRH and metoclopramide. Sperm quality (sperm mass, spermatozoa concentration and sperm motility and velocity) was evaluated 24, 48 and 72 h after hormonal treatments. Males did not release sperm in the control group injected with physiological solution, while sperm could not be collected 7 days after treatments in all hormonally treated groups. Spermiation rates were 100 % in the CPE and Ovopel groups and 25-50 % in the GnRHa-treated groups. Sperm production was significantly lower in the GnRHa-treated groups than in the CPE and Ovopel groups and decreased 72 h after hormonal treatment. Sperm motility and velocity were higher in the Ovopel and GnRHa (75 μg) groups compared to the CPE and GnRHa (25 μg) groups and decreased 72 h after hormonal treatment. Androgens were only affected in spermiating males and changed in the Ovopel and GnRHa (75 μg) after hormonal treatment. Significant correlations were observed between sperm production, sperm motility and sperm velocity, but not androgens. The present study suggests involvement of dopamine in sturgeon spawning. Additionally, better sperm quality observed in the Ovopel group and particularly sperm motility in the GnRHa (75 μg) suggests enhancement of sperm quality in sturgeon treated with GnRHa. Therefore, further study is needed to induce fully spermiation using GnRHa implants in combination with a dopamine inhibitor.

  4. High Serum Estradiol and Heavy Metals Responsible for Human Spermiation Defect-A Pilot Study

    PubMed Central

    Jain, Manish; Kalsi, Amanpreet Kaur; Srivastava, Amita; Gupta, Yogendra Kumar

    2016-01-01

    Introduction Spermiation is a process of releasing sperm into the lumen of seminiferous tubules. Failure in releasing sperm into the lumen is designated as spermiation defect. Spermiation defect cases present as oligo-azoospermia or azoospermia despite normal gonadotropins and testicular histology/cytology. Human spermiation defect never got attention to investigate infertility practice. Most of the information on spermiation defect, so far is from animal experiments. We assume some cases of non-obstructive azoospermia with normal gonadotropins and testicular histology/cytology could be due to spermiation defect. Aim The aim of the study was to find out the underlying aetiology in cases of human spermiation defect. Materials and Methods A total of 13 cases of spermiation defect and 20 fertile men as control constituted study material. Cases were studied for chromosomal abnormalities by conventional karyotyping, sex chromosome mosaicism by interphase XY FISH, Yq microdeletion by STS PCR, sertoli cell quality (function) and quantity (numbers) by serum Anti-Mullerian Hormone (AMH) and inhibin B besides other hormones like Follicular Stimulating Hormone (FSH), prolactin, testosterone and estradiol. Vitamin A concentration in serum was also measured. Presence of heavy metal was investigated by elemental electron microscopy in seminal cells (eight cases) & by spectrometry in serum as well as seminal plasma. Results Chromosomal and Yq microdeletion study failed to detect any abnormalities. AMH, inhibin B and vitamin A were also normal. Estradiol level was high in 6 out of 13 cases (46%) while platinum in seminal cells was high in 4 cases (50%). High (four times or more) serum level of lead and nickel was observed in 11 (85%) and 6 (46%) cases, respectively. Conclusion High serum concentration of heavy metals like lead & nickel or high platinum accumulation in seminal cells or high serum estradiol alone or in combinations may be underlying aetiologic factors in human

  5. Actin binding proteins, spermatid transport and spermiation*

    PubMed Central

    Qian, Xiaojing; Mruk, Dolores D.; Cheng, Yan-Ho; Tang, Elizabeth I.; Han, Daishu; Lee, Will M.; Wong, Elissa W. P.; Cheng, C. Yan

    2014-01-01

    The transport of germ cells across the seminiferous epithelium is composed of a series of cellular events during the epithelial cycle essential to the completion of spermatogenesis. Without the timely transport of spermatids during spermiogenesis, spermatozoa that are transformed from step 19 spermatids in the rat testis fail to reach the luminal edge of the apical compartment and enter the tubule lumen at spermiation, thereby entering the epididymis for further maturation. Step 19 spermatids and/or sperms that remain in the epithelium will be removed by the Sertoli cell via phagocytosis to form phagosomes and be degraded by lysosomes, leading to subfertility and/or infertility. However, the biology of spermatid transport, in particular the final events that lead to spermiation remain elusive. Based on recent data in the field, we critically evaluate the biology of spermiation herein by focusing on the actin binding proteins (ABPs) that regulate the organization of actin microfilaments at the Sertoli-spermatid interface, which is crucial for spermatid transport during this event. The hypothesis we put forth herein also highlights some specific areas of research that can be pursued by investigators in the years to come. PMID:24735648

  6. Effects of luteinizing hormone-releasing hormone and arginine-vasotocin on the sperm-release response of Günther's Toadlet, Pseudophryne guentheri

    PubMed Central

    2010-01-01

    Background Luteinizing hormone-releasing hormone (LHRH) is an exogenous hormone commonly used to induce spermiation in anuran amphibians. Over the past few decades, the LHRH dose administered to individuals and the frequency of injection has been highly variable. The sperm-release responses reported have been correspondingly diverse, highlighting a need to quantify dose-response relationships on a species-specific basis. This study on the Australian anuran Pseudophryne guentheri first evaluated the spermiation response of males administered one of five LHRHa doses, and second, determined whether AVT administered in combination with the optimal LHRHa dose improved sperm-release. Methods Male toadlets were administered a single dose of 0, 1, 2, 4 or 8 micrograms/g body weight of LHRHa. A 4 micrograms/g dose of AVT was administered alone or in combination with 2 micrograms/g LHRHa. Spermiation responses were evaluated at 3, 7 and 12 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Results LHRHa administration was highly effective at inducing spermiation in P. guentheri, with 100% of hormone-treated males producing sperm during the experimental period. The number of sperm released in response to 2 micrograms/g LHRHa was greater than all other doses administered and sperm viability was highest in the 1 microgram/g treatment. The administration of AVT alone or in combination with LHRHa resulted in the release of significantly lower sperm numbers. Conclusion Overall, results from this study suggest that in P. guentheri, LHRHa is effective at inducing spermiation, but that AVT inhibits sperm-release. PMID:21059269

  7. Hormone activation induces nucleosome positioning in vivo

    PubMed Central

    Belikov, Sergey; Gelius, Birgitta; Almouzni, Geneviève; Wrange, Örjan

    2000-01-01

    The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone. PMID:10698943

  8. Induction of spermatogenesis and spermiation by a single injection of human chorionic gonadotropin in intact and hypophysectomized immature European eel (Anguilla anguilla L.).

    PubMed

    Khan, I A; Lopez, E; Leloup-Hâtey, J

    1987-10-01

    Intact and hypophysectomized male silver eels (Anguilla anguilla) in fresh water received a single injection of human chorionic gonadotropin (hCG) (250 C) or solvent (0.15 M NaCl). No effect of solvent was observed. Spermatogonia proliferated in testis of hCG-treated intact or hypophysectomized eels. One month after the injection, primary and secondary spermatocytes were found. After 3 months, numerous spermatozoa were present. In hypophysectomized eels, hCG was also effective even though maturing germ cells were less numerous and spermiation was less frequent than in intact animals. Within 1 week after hCG injection, plasma levels of free and glucuroconjugated androgens (testosterone and 11-oxotestosterone) rose significantly in intact and hypophysectomized fish. The highest values were observed within 1 month, and then plasma levels decreased to pretreatment values. The most important changes were observed in the case of free 11-oxotestosterone. The long-term effects of hCG can be explained partly by the long half-life of this hormone. The effects of hypophysectomy on the response of testis to hCG caused us to think that some endogenous pituitary secretions must interfere in the intact fish so that maximal effects of hCG, especially on the induction of spermiation, are obtained.

  9. Thyroid hormones induce browning of white fat

    PubMed Central

    Martínez-Sánchez, Noelia; Moreno-Navarrete, José M; Contreras, Cristina; Rial-Pensado, Eva; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos

    2016-01-01

    The canonical view about the effect of thyroid hormones (THs) on thermogenesis assumes that the hypothalamus acts merely as a modulator of the sympathetic outflow on brown adipose tissue (BAT). Recent data have challenged that vision by demonstrating that THs act on the ventromedial nucleus of the hypothalamus (VMH) to inhibit AMP-activated protein kinase (AMPK), which regulates the thermogenic program in BAT, leading to increased thermogenesis and weight loss. Current data have shown that in addition to activation of brown fat, the browning of white adipose tissue (WAT) might also be an important thermogenic mechanism. However, the possible central effects of THs on the browning of white fat remain unclear. Here, we show that 3,3′,5,5′ tetraiodothyroxyne (T4)-induced hyperthyroidism promotes a marked browning of WAT. Of note, central or VMH-specific administration of 3,3′,5-triiodothyronine (T3) recapitulates that effect. The specific genetic activation of hypothalamic AMPK in the VMH reversed the central effect of T3 on browning. Finally, we also showed that the expression of browning genes in human WAT correlates with serum T4. Overall, these data indicate that THs induce browning of WAT and that this mechanism is mediated via the central effects of THs on energy balance. PMID:27913573

  10. Asprosin, a fasting-induced glucogenic protein hormone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is t...

  11. Stimulation of Spermiation by Human Chorionic Gonadotropin and Carp Pituitary Extract in Grass Puffer, Takifugu niphobles

    PubMed Central

    Goo, In Bon; Park, In-Seok; Gil, Hyun Woo; Im, Jae Hyun

    2015-01-01

    Spermiation was stimulated in the mature grass puffer, Takifugu niphobles, with an injection of human chorionic gonadotropin (HCG) or carp pituitary extract (CPE). Spermatocrit and sperm density were reduced, but milt production was increased in both the HCG and CPE treatment groups relative to those in the control group (P <0.05). These results should be useful for increasing the fertilization efficiency in grass puffer breeding programs. PMID:26973977

  12. Effects of hypothalamic dopamine on growth hormone-releasing hormone-induced growth hormone secretion and thyrotropin-releasing hormone-induced prolactin secretion in goats.

    PubMed

    Jin, Jin; Hashizume, Tsutomu

    2015-06-01

    The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH-releasing response to an intravenous (i.v.) injection of GH-releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L-dopa (1 mg/kg BW) in male and female goats under a 16-h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L-dopa treatments completely suppressed GH-releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)-releasing response to an i.v. injection of thyrotropin-releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L-dopa significantly reduced TRH-induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats.

  13. A developmental switch induced by thyroid hormone: Xenopus laevis metamorphosis.

    PubMed

    Furlow, J David; Neff, Eric S

    2006-03-01

    Thyroid hormone induces the complete metamorphosis of anuran tadpoles into juvenile frogs. Arguably, anuran metamorphosis is the most dramatic effect of a hormone in any vertebrate. Recent advances in pharmacology and molecular biology have made the study of this remarkable process in the frog Xenopus laevis attractive to developmental biologists and endocrinologists alike. In particular, the availability of a straightforward transgenesis assay and the near completion of the Xenopus tropicalis genome are enabling significant advances to be made in our understanding of the major remaining problems of metamorphosis: the extraordinary tissue specificity of responses, the precise timing of morphological changes, the degree of cell autonomy of hormone responses and developmental competence. We argue that X. laevis metamorphosis presents an exciting opportunity for understanding the role of thyroid hormone in vertebrate development.

  14. Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility

    PubMed Central

    Qian, Xu; Wang, Lin; Zheng, Bo; Shi, Zhu-Mei; Ge, Xin; Jiang, Cheng-Fei; Qian, Ying-Chen; Li, Dong-Mei; Li, Wei; Liu, Xue; Yin, Yu; Zheng, Ji-Tai; Shen, Hua; Wang, Min; Guo, Xue-Jiang; He, Jun; Lin, Marie; Liu, Ling-Zhi; Sha, Jia-Hao; Jiang, Bing-Hua

    2016-01-01

    Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation. PMID:28008940

  15. Thyrotrophin-releasing hormone induces growth hormone secretion in adult hypothyroid fowl.

    PubMed

    Harvey, S; Scanes, C G; Klandorf, H

    1988-02-01

    While thyrotrophin-releasing hormone (TRH) stimulated growth hormone (GH) secretion in adult anesthetized cockerels, the GH response was blocked in anesthetized birds pretreated with thyroxine (T4) or triiodothyronine (T3). Moreover, whereas GH secretion in conscious adult birds was poorly responsive to TRH stimulation, conscious birds made hypothyroid by goitrogen pretreatment (with propylthiouracil, methimazole, or thiourea) were responsive to TRH challenge. Basal circulating GH concentrations in the goitrogen-pretreated birds were also higher than in the vehicle-injected controls. Surgical thyroidectomy similarly increased the basal GH concentration in adult birds and promoted TRH-induced GH secretion. These results demonstrate inhibitory effects of the thyroid hormones on basal and stimulated GH secretion in adult domestic fowl and suggest that GH release in adults is partly under tonic thyroidal inhibition.

  16. Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

    PubMed

    Romere, Chase; Duerrschmid, Clemens; Bournat, Juan; Constable, Petra; Jain, Mahim; Xia, Fan; Saha, Pradip K; Del Solar, Maria; Zhu, Bokai; York, Brian; Sarkar, Poonam; Rendon, David A; Gaber, M Waleed; LeMaire, Scott A; Coselli, Joseph S; Milewicz, Dianna M; Sutton, V Reid; Butte, Nancy F; Moore, David D; Chopra, Atul R

    2016-04-21

    Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

  17. CYP1B1 and hormone-induced cancer.

    PubMed

    Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L

    2012-11-01

    Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.

  18. Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release

    PubMed Central

    Ignacio, Daniele Leão; da S. Silvestre, Diego H.; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade

    2015-01-01

    Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

  19. Gravity-induced asymmetric distribution of a plant growth hormone

    NASA Technical Reports Server (NTRS)

    Bandurski, R. S.; Schulze, A.; Momonoki, Y.

    1984-01-01

    Dolk (1936) demonstrated that gravistimulation induced an asymmetric distribution of auxin in a horizontally-placed shoot. An attempt is made to determine where and how that asymmetry arises, and to demonstrate that the endogenous auxin, indole-3-acetic acid, becomes asymmetrically distributed in the cortical cells of the Zea mays mesocotyl during 3 min of geostimulation. Further, indole-3-acetic acid derived by hydrolysis of an applied transport form of the hormone, indole-3-acetyl-myo-inositol, becomes asymmetrically distributed within 15 min of geostimulus time. From these and prior data is developed a working theory that the gravitational stimulus induces a selective leakage, or secretion, of the hormone from the vascular tissue to the cortical cells of the mesocotyl.

  20. SERUM HORMONE CHARACTERIZATION AND EXOGENEOUS HORMONE RESCUE OF BROMODICHLOROMETHANE-INDUCED PREGNANCY LOSS IN THE F344 RAT

    EPA Science Inventory

    SERUM HORMONE CHARACTERIZATION AND EXOGENEOUS HORMONE RESCUE OF BROMODICHLOROMETHANE-INDUCED
    PREGNANCY LOSS IN THE F344 RAT
    Susan R. Bielmeier*, Deborah S. Best^, and Michael G. Narotsky^

    ABSTRACT
    Previously, we demonstrated that bromodichloromethane (BDCM), a d...

  1. Hormonal induction of spermatozoa from amphibians with Rana temporaria and Bufo bufo as anuran models.

    PubMed

    Uteshev, V K; Shishova, N V; Kaurova, S A; Browne, R K; Gakhova, E N

    2012-01-01

    The use of hormonally induced spermatozoa expressed in urine (HISu) is a valuable component of reproduction technologies for amphibians. Five protocols for sampling HISu from the European common frog (Rana temporaria) were compared: (1) pituitary extracts, (2) 0.12 µg g⁻¹ luteinising hormone-releasing hormone analogue (LHRHa), (3) 1.20 µg g⁻¹ LHRHa, (4) 11.7 IU g⁻¹ human chorionic gonadotrophin (hCG) and (5) 23.4 IU g⁻¹ hCG (g⁻¹ = per gram bodyweight). From 1 to 24h after administration we assessed the number and concentration of spermatozoa in spermic urine and in holding water, and in urine the percentage of motile spermatozoa and their progressive motility. The protocol using 1.20 µg g⁻¹ LHRHa gave the highest total sperm numbers (650 × 10⁶) and the highest percentage (40%) of samples with sperm concentrations above 200 × 10⁶ mL⁻¹. The percentage motility and progressive motility was similar from all protocols. Considerable amounts of spermatozoa were expressed by R. temporaria into their holding water. We tested hormonal priming and spermiation in the common toad (Bufo bufo) using 0.13 µg g⁻¹ LHRHa administered 24h before a final spermiating dose of 12.8 IU g⁻¹ hCG. No spermatozoa were expressed in holding water. Priming resulted in 35% more spermatozoa than without; however, there were no differences in sperm concentrations. Primed B. bufo produced spermatozoa with significantly higher percentage motility, but not progressive motility, membrane integrity, or abnormal spermatozoa than unprimed males.

  2. Quetiapine-Induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone.

    PubMed

    Koufakis, Theocharis

    2016-01-01

    The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can be induced by various conditions, including malignant neoplasms, infections, central nervous system disorders, and numerous drugs. We here report a case of a 65-year-old female patient, treated with quetiapine for schizophrenia, who presented with generalized tonic-clonic seizures and was finally diagnosed with quetiapine-induced SIADH. Quetiapine-associated hyponatremia is extremely uncommon and only a few, relevant reports can be found in the literature. This case underlines the fact that patients on antipsychotic medication and more specifically on quetiapine should be closely monitored and routinely tested for electrolyte disorders.

  3. Corticotropin-releasing hormone mediates alpha-melanocyte-stimulating hormone-induced anorexigenic action in goldfish.

    PubMed

    Matsuda, Kouhei; Kojima, Kenji; Shimakura, Sei-Ichi; Wada, Kohei; Maruyama, Keisuke; Uchiyama, Minoru; Kikuyama, Sakae; Shioda, Seiji

    2008-11-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) and corticotropin-releasing hormone (CRH) both suppress food intake, and the alpha-MSH- or CRH-signaling pathway has possible potency to mediate anorexigenic actions induced by most other neuropeptides in goldfish. Therefore, using specific receptor antagonists, we examined whether the anorexigenic actions of alpha-MSH and CRH mutually interact. The inhibitory effect of ICV injection of the alpha-MSH agonist, melanotan II (MT II), on food intake was abolished by treatment with a CRH 1/2 receptor antagonist, alpha-helical CRH((9-41)), whereas the anorexigenic action of ICV-injected CRH was not affected by treatment with a melanocortin 4 receptor antagonist, HS024. This led us to investigate whether alpha-MSH-containing neurons in the goldfish brain have direct inputs to CRH-containing neurons, using confocal laser scanning microscopy. alpha-MSH- and CRH-like immunoreactivities were distributed throughout the brain, especially in the diencephalon. alpha-MSH-containing nerve fibers or endings lay in close apposition to CRH-containing neurons in a region of the hypothalamus, the nucleus posterioris periventricularis (NPPv). These results indicate that, in goldfish, alpha-MSH-induced anorexigenic action is mediated by the CRH-signaling pathway, and that CRH plays a crucial role in the regulation of feeding behavior as an integrated anorexigenic neuropeptide in this species.

  4. Spermiogenesis and spermiation in a monotreme mammal, the platypus, Ornithorhynchus anatinus.

    PubMed

    Lin, M; Jones, R C

    2000-02-01

    Spermatogenesis in the platypus (Ornithorhynchus anatinus) is of considerable biological interest as the structure of its gametes more closely resemble that of reptiles and birds than marsupial or eutherian mammals. The ultrastructure of 16 steps of spermatid development is described and provides a basis for determining the kinetics of spermatogenesis. Steps 1-3 correspond to the Golgi phase of spermatid development, steps 4-8 correspond to the cap phase, steps 9-12 are the acrosomal phase, and steps 13-16 are the maturation phase. Acrosomal development follows the reptilian model and no acrosomal granule is formed. Most other features of spermiogenesis are similar to processes in reptiles and birds. However, some are unique to mammals. For example, a thin, lateral margin of the acrosome of platypus sperm expands over the nucleus as in other mammals, and more than in reptiles and birds. Also, a tubulobulbar complex develops around the spermatid head, a feature which appears to be unique to mammals. Further, during spermiation the residual body is released from the caudal end of the nucleus of platypus sperm leaving a cytoplasmic droplet located at the proximal end of the middle piece as in marsupial and eutherian mammals. Other features of spermiogenesis in platypus appear to be unique to monotremes. For example, nuclear condensation involves the formation of a layer of chromatin granules under the nucleolemma, and development of the fibrous sheath of the principal piece starts much later in the platypus than in birds or eutherian mammals.

  5. Spermiogenesis and spermiation in a monotreme mammal, the platypus, Ornithorhynchus anatinus

    PubMed Central

    LIN, MINJIE; JONES, RUSSELL C.

    2000-01-01

    Spermatogenesis in the platypus (Ornithorhynchus anatinus) is of considerable biological interest as the structure of its gametes more closely resemble that of reptiles and birds than marsupial or eutherian mammals. The ultrastructure of 16 steps of spermatid development is described and provides a basis for determining the kinetics of spermatogenesis. Steps 1–3 correspond to the Golgi phase of spermatid development, steps 4–8 correspond to the cap phase, steps 9–12 are the acrosomal phase, and steps 13–16 are the maturation phase. Acrosomal development follows the reptilian model and no acrosomal granule is formed. Most other features of spermiogenesis are similar to processes in reptiles and birds. However, some are unique to mammals. For example, a thin, lateral margin of the acrosome of platypus sperm expands over the nucleus as in other mammals, and more than in reptiles and birds. Also, a tubulobulbar complex develops around the spermatid head, a feature which appears to be unique to mammals. Further, during spermiation the residual body is released from the caudal end of the nucleus of platypus sperm leaving a cytoplasmic droplet located at the proximal end of the middle piece as in marsupial and eutherian mammals. Other features of spermiogenesis in platypus appear to be unique to monotremes. For example, nuclear condensation involves the formation of a layer of chromatin granules under the nucleolemma, and development of the fibrous sheath of the principal piece starts much later in the platypus than in birds or eutherian mammals. PMID:10739018

  6. Hormones

    MedlinePlus

    ... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...

  7. Cryopreservation of hormonally induced sperm for the conservation of threatened amphibians with Rana temporaria as a model research species.

    PubMed

    Shishova, N R; Uteshev, V K; Kaurova, S A; Browne, R K; Gakhova, E N

    2011-01-15

    The survival of hundreds of threatened amphibian species is increasingly dependent on conservation breeding programs (CBPs). However, there is an ongoing loss of genetic variation in CBPs for most amphibians, reptiles, birds, and mammals. Low genetic variation results in the failure of CBPs to provide genetically competent individuals for release in supplementation or rehabitation programs. In contrast, in the aquaculture of fish the perpetuation of genetic variation and the production of large numbers of genetically competent individuals for release is accomplished through the cryopreservation of sperm. Successful protocols for the cryopreservation of amphibian sperm from excised testes, and the use of motile frozen then thawed sperm for fertilisation, have been adapted from those used with fish. However, there have been no protocols published for the cryopreservation of amphibian hormonally induced sperm (HIS) that have achieved fertility. We investigated protocols for the cryopreservation of amphibian HIS with the European common frog (Rana temporaria) as a model research species. We induced spermiation in R. temporaria through the intraperitoneal administration of 50 μg LHRHa and sampled HIS through expression in spermic urine. Highly motile HIS at a concentration of 200 × 10(6)/mL was then mixed 1:1 with cryodiluents to form cryosuspensions. Initial studies showed that; 1) concentrations of ∼15 × 10(6)/mL of HIS achieve maximum fertilisation, 2) TRIS buffer in cryodiluents did not improve the recovery of sperm after cryopreservation, and 3) high concentrations of DMSO (dimethylsulphoxide) cryoprotectant reduce egg and larval survival. We then compared four optimised cryopreservation protocols for HIS with the final concentrations of cryodiluents in cryosuspensions of; 1) DMSO, (½ Ringer Solution (RS), 10% sucrose, 12% DMSO); 2) DMSO/egg yolk, (½ RS, 10% sucrose, 12% DMSO, 10% egg yolk), 3) DMFA, (½ RS, 10% sucrose, 12% dimethylformamide (DMFA)), and 4

  8. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  9. Role of hormone imbalance in transplacental carcinogenesis induced in Syrian golden hamsters by sex hormones.

    PubMed

    Rustia, M

    1979-05-01

    Data are presented from studies on Syrian golden hamsters with the ENU precursors, EU, and NaNO2, given transplacentally and in adulthood, and with transplacentally administered DES. Hormone modification by gonadectomy of offspring prenatally exposed to ENU caused a significantly greater incidence and multiplicity of PNS neoplasms and other tumor types in orchidectomized males, compared with intact males, and in ovariectomized and intact females. That PNS tumors in gonadectomized males appeared within a significantly shorter latency period indicated that endogenously generated androgens inhibited neoplastic development. The endocrine imbalance also induced a higher incidence of neoplasia in other tissues and organs, e.g., skin melanomas, thyroid and adrenal cortex tumors, and notably gliomas in the CNS of ovariectomized female siblings. Exposure to single doses of ENU on days 12, 13, 14, and/or 15 caused PNS tumors predominantly in females and with an increased frequency in progeny treated during the final days of gestation. The spectrum of neoplasms was greater and their incidence significant in ENU-treated adult hamsters; the tumor types different from those of transplacentally treated animals (i.e., vascular, vaginal, and ovarian tumors and fore-stomach papillomas were seen). Determining factors in carcinogenesis at the time of carcinogen treatment possibly included stage of ontogenic development, degree of cell differentiation, hormone state of host, age, total dose, and duration of treatment. DES results indicated that the haster may be a useful model for reproducing lesions similar to those observed in children of mothers treated with this drug during pregnancy.

  10. Hormones and Obesity: Changes in Insulin and Growth Hormone Secretion Following Surgically Induced Weight Loss

    PubMed Central

    Crockford, P. M.; Salmon, P. A.

    1970-01-01

    Ten obese patients were subjected to insulin tolerance tests (0.2 unit per kg. regular insulin intravenously) and/or treadmill exercise tolerance testing (2.6 m.p.h. at 11° angulation) before and after surgically induced weight reduction. Immunoreactive growth hormone (IRGH) responses returned to normal with weight reduction in all but one—a grossly obese woman studied relatively early in the postoperative period when still far from the ideal body weight. Five of these patients and two additional subjects had intravenous glucose tolerance tests (0.5 g. per kg.) before and after weight reduction. In all, there was a significant diminution in immunoreactive insulin (IRI) values, accompained by little or no change in the glucose disappearance rate (KG) and a significant improvement in insulin effectiveness as indicated by the calculated “insulinogenic index”. It was concluded that the abnormalities in IRGH and IRI secretion, as well as the insulin resistance in obesity, are probably secondary and not of primary importance in the etiology of this disorder. PMID:5430052

  11. The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics.

    PubMed

    Lucas, Julia N; Rudmann, Daniel G; Credille, Kelly M; Irizarry, Armando R; Peter, Augustine; Snyder, Paul W

    2007-02-01

    The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes.

  12. Attenuation of kindling-induced decreases in NT-3 mRNA by thyroid hormone depletion.

    PubMed

    Kim, S Y; Smith, M A; Post, R M; Rosen, J B

    1998-02-01

    The expression of neurotrophins is altered by amygdala kindled seizures. Because thyroid hormone can regulate the transcription of neurotrophins, we asked whether thyroid hormone regulates neurotrophin mRNA expression following amygdala kindling. Rats with electrodes implanted in the basolateral nucleus of the amygdala were either depleted of thyroid hormone or given excess thyroid hormone. The rats were then kindled daily until they had one generalized seizure. The brains were removed 4 h after the seizure and processed for in situ hybridization of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs. In non-kindled rats, thyroid hormone depletion increased the levels of BDNF mRNA in the paraventricular nucleus of the hypothalamus and the pituitary gland. NGF and NT-3 mRNA expression was not altered. In addition, thyroid hormone manipulations had no effect on kindling or on kindling-induced BDNF and NGF mRNA. However, the kindling-induced decrease in NT-3 mRNA expression in the dentate gyrus granule cell layer was significantly attenuated by thyroid hormone depletion. These effects were reversed by thyroid hormone replacement. The results indicate that thyroid hormone plays a modulatory role in the seizure-induced changes of NT-3 mRNA expression found in the dentate gyrus.

  13. Hormone induced changes in lactase glycosylation in developing rat intestine.

    PubMed

    Chaudhry, Kamaljit Kaur; Mahmood, Safrun; Mahmood, Akhtar

    2008-11-01

    Lactase exists in both soluble and membrane-bound forms in suckling rat intestine. The distribution of lactase and its glycosylated isoforms in response to thyroxine or cortisone administration has been studied in suckling rats. 75% of lactase activity was detected, associated with brush borders, compared to 24% in the soluble fraction of 8-day-old rats. Thyroxine treatment enhanced soluble lactase activity to 34%, whereas particulate fraction was reduced to 67% compared to controls. Cortisone administration reduced soluble lactase activity from 24% in controls to 12% with a concomitant increase in membrane-bound activity to 89%. Western blot analysis revealed lactase signal, corresponding to 220 kDa in both the soluble and membrane fractions, which corroborated the enzyme activity data. The elution pattern of papain solubilized lactase from agarose-Wheat Germ agglutinin, or Concanavalin A or Jacalin agglutinin columns was different in the suckling and adult rat intestines. Also the elution profile of lactase activity from agarose-lectin columns was modulated in cortisone, thyroxine, and insulin injected pups, which suggests differences in glycosylated isoforms of lactase under these conditions. These findings suggest the role of these hormones in inducing changes in lactase glycosylation during postnatal development of intestine, which may contribute to adult-type hypolactasia in rats.

  14. Hormonal relations of radiation-induced tumors of Arabidopsis thaliana

    SciTech Connect

    Campell, B.R.; Persinger, S.M.; Town, C.D. )

    1989-04-01

    When gamma-irradiated Arabidopsis seed was germinated, tumors appeared on hypocotyls and apical meristems of the resulting plants. Several tumors have been cultured on hormone free medium for over two years since excision from the plants. The tumor lines display a range of phenotypes suggestive of abnormal hormone balance. To determine whether hormone overproduction or hypersensitivity is involved in tumorigenesis, we are measuring hormone levels in the tumor lines and characterizing their response to exogenously supplied growth regulators. Growth of two tumor lines is stimulated by either NAA or BAP, one is stimulated by NAA only, two by BAP only, and one is stimulated by neither. Growth of all lines tested thus far is inhibited by gibberellic acid, ethephon and ACC. The tumor lines appear more sensitive to ACC than normal callus tissue. Most tumors studied to date appear unlikely to have arisen due to increased hormone sensitivity. Experiments are in progress to determine auxin and cytokinin levels in the tumor lines.

  15. Exercise‐Induced growth hormone during acute sleep deprivation

    PubMed Central

    Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

    2014-01-01

    Abstract The effect of acute (24‐h) sleep deprivation on exercise‐induced growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24‐h sessions including a brief, high‐intensity exercise bout following either a night of sleep (SLEEP) or (24‐h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30‐sec Wingate sprints on a cycle ergometer. Self‐reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise‐induced peak GH concentration (TTP), or free IGF‐1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P <0.01), exercise‐induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P <0.01) and ΔGH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise‐induced GH response was significantly augmented in sleep‐deprived individuals. PMID:25281616

  16. Exercise-Induced growth hormone during acute sleep deprivation.

    PubMed

    Ritsche, Kevin; Nindl, Bradly C; Wideman, Laurie

    2014-10-01

    The effect of acute (24-h) sleep deprivation on exercise-induced growth hormone (GH) and insulin-like growth factor-1 (IGF-1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24-h sessions including a brief, high-intensity exercise bout following either a night of sleep (SLEEP) or (24-h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30-sec Wingate sprints on a cycle ergometer. Self-reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P = 0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P = 0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise-induced peak GH concentration (TTP), or free IGF-1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P < 0.01), exercise-induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P < 0.01) and ΔGH (peak GH - resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P < 0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise-induced GH response was significantly augmented in sleep-deprived individuals.

  17. The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction

    PubMed Central

    Bansal, Vishal; Ryu, Seok Yong; Blow, Chelsea; Costantini, Todd; Loomis, William; Eliceiri, Brian; Baird, Andrew; Wolf, Paul

    2010-01-01

    Abstract Intestinal barrier breakdown following traumatic brain injury (TBI) is characterized by increased intestinal permeability, leading to bacterial translocation, and inflammation. The hormone ghrelin may prevent intestinal injury and have anti-inflammatory properties. We hypothesized that exogenous ghrelin prevents intestinal injury following TBI. A weight-drop model created severe TBI in three groups of anesthetized Balb/c mice. Group TBI: animals underwent TBI only; Group TBI/ghrelin: animals were given 10 μg of ghrelin intraperitoneally prior and 1 h following TBI; Group sham: no TBI or ghrelin injection. Intestinal permeability was measured 6 h following TBI by detecting serum levels of FITC-Dextran after injection into the intact ileum. The terminal ileum was harvested for histology, expression of the tight junction protein MLCK and inflammatory cytokine TNF-α. Permeability increased in the TBI group compared to the sham group (109.7 ± 21.8 μg/mL vs. 32.2 ± 10.1 μg/mL; p < 0.002). Ghrelin prevented TBI-induced permeability (28.3 ± 4.2 μg/mL vs. 109.7 ± 21.8 μg/mL; p < 0.001). The intestines of the TBI group showed blunting and necrosis of villi compared to the sham group, while ghrelin injection preserved intestinal architecture. Intestinal MLCK increased 73% compared to the sham group (p < 0.03). Ghrelin prevented TBI-induced MLCK expression to sham levels. Intestinal TNF-α increased following TBI compared to the sham group (46.2 ± 7.1 pg/mL vs. 24.4 ± 2.2 pg/mL p < 0.001). Ghrelin reduced TNF-α to sham levels (29.2 ± 5.0 pg/mL; p = NS). We therefore conclude that ghrelin prevents TBI-induced injury, as determined by intestinal permeability, histology, and intestinal levels of TNF-α. The mechanism for ghrelin mediating intestinal protection is likely multifactorial, and further studies are needed to delineate these possibilities. PMID:20858122

  18. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    EPA Science Inventory

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  19. Effects of a Model Inducer, Phenobarbital, on Thyroid Hormone Glucuronidation in Rat Hepatocytes

    EPA Science Inventory

    In vivo, hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations. This decrease in circulating TH occurs in part through extrathyroidal mechanisms. Specifically, through the induction of hepatic xenobiotic metabolizing enzymes...

  20. Impact of Low-Level Thyroid Hormone Disruption Induced by Propylthiouracil on Brain Development and Function.*

    EPA Science Inventory

    The critical role of thyroid hormone (TH) in brain development is well established, severe deficiencies leading to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degr...

  1. Role of the Stem Cell Niche in Hormone-Induced Tumorigenesis in Fetal Mouse Mammary Epithelium

    DTIC Science & Technology

    2005-08-01

    AD Award Number: W81XWH-04-1-0719 TITLE: Role of the Stem Cell Niche in Hormone-Induced Tumorigenesis in Fetal Mouse Mammary Epithelium PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse 5b. GRANT NUMBER Mammary Epithelium...SUPPLEMENTARY NOTES 14. ABSTRACT SEE PAGE 4 15. SUBJECT TERMS Stem Cells , Stem Cell niche, Immunohistochemistry, mammary gland, breast cancer 16

  2. Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

    SciTech Connect

    Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

    1985-08-01

    Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation.

  3. Gastrointestinal Hormones and Bariatric Surgery-induced Weight Loss

    PubMed Central

    Ionut, Viorica; Burch, Miguel; Youdim, Adrienne; Bergman, Richard N.

    2015-01-01

    Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity. Objective To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance. Design and Methods The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity. Results The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption. Conclusion Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss. PMID:23512841

  4. Normal breast physiology: the reasons hormonal contraceptives and induced abortion increase breast-cancer risk.

    PubMed

    Lanfranchi, Angela

    2014-01-01

    A woman gains protection from breast cancer by completing a full-term pregnancy. In utero, her offspring produce hormones that mature 85 percent of the mother's breast tissue into cancer-resistant breast tissue. If the pregnancy ends through an induced abortion or a premature birth before thirty-two weeks, the mother's breasts will have only partially matured, retaining even more cancer-susceptible breast tissue than when the pregnancy began. This increased amount of immature breast tissue will leave the mother with more sites for cancer initiation, thereby increasing her risk of breast cancer. Hormonal contraceptives increase breast-cancer risk by their proliferative effect on breast tissue and their direct carcinogenic effects on DNA. Hormonal contraceptives include estrogen-progestin combination drugs prescribed in any manner of delivery: orally, transdermally, vaginally, or intrauterine. This article provides the detailed physiology and data that elucidate the mechanisms through which induced abortion and hormonal contraceptives increase breast-cancer risk.

  5. Diacylglycerol production induced by growth hormone in Ob1771 preadipocytes arises from phosphatidylcholine breakdown

    SciTech Connect

    Catalioto, R.M.; Ailhaud, G.; Negrel, R. )

    1990-12-31

    Growth Hormone has recently been shown to stimulate the formation of diacylglycerol in Ob1771 mouse preadipocyte cells without increasing inositol lipid turnover. Addition of growth hormone to Ob1771 cells prelabelled with ({sup 3}H)glycerol or ({sup 3}H)choline led to a rapid, transient and stoechiometric formation of labelled diacylglycerol and phosphocholine, respectively. In contrast, no change was observed in the level of choline and phosphatidic acid whereas the release of water-soluble metabolites in ({sup 3}H)ethanolamine prelabelled cells exposed to growth hormone was hardly detectable. Stimulation by growth hormone of cells prelabelled with (2-palmitoyl 9, 10 ({sup 3}H))phosphatidylcholine also induced the production of labelled diacyglycerol. Pertussis toxin abolished both diacylglycerol and phosphocholine formation induced by growth hormone. It is concluded that growth hormone mediates diacylglycerol production in Ob1771 cells by means of phosphatidylcholine breakdown involving a phospholipase C which is likely coupled to the growth hormone receptor via a pertussis toxin-sensitive G-protein.

  6. (−)-Epigallocatechin-3-gallate induces secretion of anorexigenic gut hormones

    PubMed Central

    Song, Won-Young; Aihara, Yoshiko; Hashimoto, Takashi; Kanazawa, Kazuki; Mizuno, Masashi

    2015-01-01

    The anorexigenic gut hormones, cholecystokinin (CCK), glucagon-like peptide (GLP)-1 and peptide tyrosine-tyrosine (PYY), are released in response to food intake from the intestines. Dietary nutrients have been shown to stimulate these hormones. Some non-nutrients such as polyphenols show anorexigenic effects on humans. In the present study, we examined whether dietary polyphenols can stimulate secretion of these gut hormones. Caco-2 cells expressed mRNA of the gut hormones, CCK, PC1 (prohormone convertase 1), GCG (glucagon) and PYY. CCK, GLP-1 and PYY were secreted from Caco-2 cells after adding sugars, amino acids or fatty acids. Using Caco-2 cells, epigallocatechin-3-gallate (EGCG), chlorogenic acid and ferulic acid induced secretion of anorexigenic gut hormones. Particularly, EGCG induced secretion of all three hormones. In an ex vivo assay using murine intestines, EGCG also released CCK from the duodenum, and GLP-1 from the ileum. These results suggest that EGCG may affect appetite via gut hormones. PMID:26388676

  7. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

    PubMed

    Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

    2013-11-01

    Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep.

  8. Sensations induced by medium and long chain triglycerides: role of gastric tone and hormones

    PubMed Central

    Barbera, R; Peracchi, M; Brighenti, F; Cesana, B; Bianchi, P; Basilisco, G

    2000-01-01

    BACKGROUND—The relative roles of gastric relaxation and the neuroendocrine signals released by the small intestine in the perception of nutrient induced sensations are controversial. The different effects of long chain (LCT) and medium chain (MCT) triglyceride ingestion on perception, gastric relaxation, and hormonal release may help to elucidate the mechanisms underlying nutrient induced sensations.
AIMS—To compare the effects of intraduodenal LCT and MCT infusions on perception, gastric tone, and plasma gut hormone levels in healthy subjects.
SUBJECTS—Nine fasting healthy volunteers.
METHODS—The subjects received duodenal infusions of saline followed by LCTs and MCTs in a randomised order on two different days. The sensations were rated on a visual analogue scale. Gastric tone was measured using a barostat, and plasma gut hormone levels by radioimmunoassay.
RESULTS—LCT infusion increased satiation scores, reduced gastric tone, and increased the levels of plasma cholecystokinin, gastric inhibitory polypeptide, neurotensin, and pancreatic polypeptide. MCT infusion reduced gastric tone but did not significantly affect perception or plasma gut hormone levels. LCTs produced greater gastric relaxation than MCTs.
CONCLUSIONS—The satiation induced by intraduodenal LCT infusion seems to involve changes in gastric tone and plasma gut hormone levels. The gastric relaxation induced by MCT infusion, together with the absence of any significant change in satiation scores and plasma hormone levels, suggests that, at least up to a certain level, gastric relaxation is not sufficient to induce satiation and that nutrient induced gastric relaxation may occur through cholecystokinin independent mechanisms.


Keywords: gastric tone; triglyceride; hormones; satiation; cholecystokinin; nutrients PMID:10601051

  9. Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

    PubMed

    Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

    2015-08-21

    Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.

  10. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    SciTech Connect

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-03-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E{sub 2}) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E{sub 2} dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E{sub 2} increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab.

  11. Growth hormone release induced by growth hormone-releasing hexapeptide is not mediated by thyrotropin-releasing hormone in neonatal rats.

    PubMed

    Kacsóh, B; Kacsóh, G; Guzzardo, M B; Black, A C; Bisat, T

    1997-02-01

    GH-releasing hexapeptide (GHRP-6) and nursing stimulate GH secretion in rat pups via GH-releasing factors (GRFs: distinct from GH-releasing hormone (GHRH). It was determined whether GH secretion induced by GHRP-6 or nursing was mediated by TSH-releasing hormone (TRH) in 2-d-old rats. In vitro. GHRP-6 and TRH stimulated GH secretion of neonatal pituitary glands. At their maximally effective doses, GHRP-6 and TRH evoked approximately equal GH responses. Treatment with a combination of the maximally effective doses of GHRP-6 and TRH resulted in a GH response comparable to that evoked by either treatment alone. GHRP-6 in vivo induced a greater GH response than did TRH. Treatment in vivo with a combination of the maximally effective doses of GHRP-6 and TRH synergistically increased serum GH levels. Unlike GHRP-6 TRH was an effective stimulus of prolactin secretion either in vitro or in vivo. Nursing was an effective stimulus for GH secretion, but only marginally increased serum prolactin levels. The effects of either of the peptides and nursing on GH secretion were additive. These results suggest that GHRP-6 stimulates GH secretion both by acting directly on the pituitary gland and indirectly via a hypothalamic GRF. The indirect effect appears to be greater. The alternative GRFs released by GHRP-6 or nursing are distinct from each other and from TRH. These findings suggest that alternative GRFs play a significant role in the regulation of GH secretion in neonatal rats.

  12. Seasonal effect of gonadotrophin inhibitory hormone on gonadotrophin-releasing hormone-induced gonadotroph functions in the goldfish pituitary.

    PubMed

    Moussavi, M; Wlasichuk, M; Chang, J P; Habibi, H R

    2013-05-01

    We have shown that native goldfish gonadotrophin inhibitory hormone (gGnIH) differentially regulates luteinsing hormone (LH)-β and follicle-stimulating hormone (FSH)-β expression. To further understand the functions of gGnIH, we examined its interactions with two native goldfish gonadotrophin-releasing hormones, salmon gonadotrophin-releasing hormone (sGnRH) and chicken (c)GnRH-II in vivo and in vitro. Intraperitoneal injections of gGnIH alone reduced serum LH levels in fish in early and mid gonadal recrudescence; this inhibition was also seen in fish co-injected with either sGnRH or cGnRH-II during early recrudescence. Injection of gGnIH alone elevated pituitary LH-β and FSH-β mRNA levels at early and mid recrudescence, and FSH-β mRNA at late recrudescence. Co-injection of gGnIH attenuated the stimulatory influences of sGnRH on LH-β in early recrudescence, and LH-β and FSH-β mRNA levels in mid and late recrudescence, as well as the cGnRH-II-elicited increase in LH-β, but not FSH-β, mRNA expression at mid and late recrudescence. sGnRH and cGnRH-II injection increased pituitary gGnIH-R mRNA expression in mid and late recrudescence but gGnIH reduced gGnIH-R mRNA levels in late recrudescence. gGnIH did not affect basal LH release from perifused pituitary cells and continual exposure to gGnIH did not alter the LH responses to acute applications of GnRH. However, a short 5-min GnIH treatment in the middle of a 60-min GnRH perifusion selectively reduced the cGnRH-II-induced release of LH. These novel results indicate that, in goldfish, gGnIH and GnRH modulate pituitary GnIH-R expression and gGnIH differentially affects sGnRH and cGnRH-II regulation of LH secretion and gonadotrophin subunit mRNA levels. Furthermore, these actions are manifested in a reproductive stage-dependent manner.

  13. Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH).

    PubMed

    Bachu, Kalyan; Godkar, Darshan; Gasparyan, Anna; Sircar, Padmini; Yakoby, Mila; Niranjan, Selvanayagam

    2006-01-01

    Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.

  14. Retinoic acid induces expression of the thyroid hormone transporter, monocarboxylate transporter 8 (Mct8).

    PubMed

    Kogai, Takahiko; Liu, Yan-Yun; Richter, Laura L; Mody, Kaizeen; Kagechika, Hiroyuki; Brent, Gregory A

    2010-08-27

    Retinoic acid (RA) and thyroid hormone are critical for differentiation and organogenesis in the embryo. Mct8 (monocarboxylate transporter 8), expressed predominantly in the brain and placenta, mediates thyroid hormone uptake from the circulation and is required for normal neural development. RA induces differentiation of F9 mouse teratocarcinoma cells toward neurons as well as extraembryonal endoderm. We hypothesized that Mct8 is functionally expressed in F9 cells and induced by RA. All-trans-RA (tRA) and other RA receptor (RAR) agonists dramatically (>300-fold) induced Mct8. tRA treatment significantly increased uptake of triiodothyronine and thyroxine (4.1- and 4.3-fold, respectively), which was abolished by a selective Mct8 inhibitor, bromosulfophthalein. Sequence inspection of the Mct8 promoter region and 5'-rapid amplification of cDNA ends PCR analysis in F9 cells identified 11 transcription start sites and a proximal Sp1 site but no TATA box. tRA significantly enhanced Mct8 promoter activity through a consensus RA-responsive element located 6.6 kilobases upstream of the coding region. A chromatin immunoprecipitation assay demonstrated binding of RAR and retinoid X receptor to the RA response element. The promotion of thyroid hormone uptake through the transcriptional up-regulation of Mct8 by RAR is likely to be important for extraembryonic endoderm development and neural differentiation. This finding demonstrates cross-talk between RA signaling and thyroid hormone signaling in early development at the level of the thyroid hormone transporter.

  15. Growth hormone resistance exacerbates cholestasis-induced murine liver fibrosis

    PubMed Central

    Stiedl, Patricia; McMahon, Robert; Blaas, Leander; Stanek, Victoria; Svinka, Jasmin; Grabner, Beatrice; Zollner, Gernot; Kessler, Sonja M.; Claudel, Thierry; Müller, Mathias; Mikulits, Wolfgang; Bilban, Martin; Esterbauer, Harald; Eferl, Robert; Haybaeck, Johannes; Trauner, Michael; Casanova, Emilio

    2016-01-01

    Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order to elucidate whether GH resistance plays a causal role in the establishment and development of liver fibrosis, or rather represents a major consequence thereof, we challenged mice lacking the Growth hormone receptor gene (Ghr-/-, a model for GH resistance) by crossing them with Mdr2 knockout mice (Mdr2-/-), a mouse model of inflammatory cholestasis and liver fibrosis. Ghr-/-;Mdr2-/- mice showed elevated serum markers associated with liver damage and cholestasis, extensive bile duct proliferation and increased collagen deposition relative to Mdr2 -/- mice, thus suggesting a more severe liver fibrosis phenotype. Additionally, Ghr-/-;Mdr2-/- mice had a pronounced down-regulation of hepato-protective genes Hnf6, Egfr and Igf-1, and significantly increased levels of ROS and apoptosis in hepatocytes, compared to control mice. Moreover, single knockout mice (Ghr-/-) fed with a diet containing 1% cholic acid displayed an increase in hepatocyte ROS production, hepatocyte apoptosis and bile infarcts compared to their wildtype littermates, indicating that loss of Ghr renders hepatocytes more susceptible to toxic bile acid accumulation. Surprisingly, and despite their severe fibrotic phenotype, Ghr-/-;Mdr2-/- mice displayed a significant decrease in tumour incidence compared to Mdr2-/- mice, indicating that loss of Ghr signaling may slow the progression from fibrosis/cirrhosis to cancer in the liver. Conclusion Our findings suggest that GH resistance dramatically exacerbates liver fibrosis in a mouse model of inflammatory cholestasis, therefore suggesting that GH resistance plays a causal role in the disease and provides a novel target for the development of liver fibrosis treatments. PMID:25179284

  16. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    SciTech Connect

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10/sup 5//well). Cells treated with GnRH Ca/sup + +/ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca/sup + +/-free media prevented the action of GnRH. GnRH caused a rapid efflux of /sup 45/Ca/sup + +/. Both GnRH-stimulated /sup 45/Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect /sup 45/Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE/sub 2/ and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca/sup + +/ does not regulate LH release; (2) GnRH elevates intracellular Ca/sup + +/ by opening both voltage sensitive and receptor mediated Ca/sup + +/ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release.

  17. Peptidal Sex Hormones Inducing Conjugation Tube Formation in Compatible Mating-Type Cells of Tremella mesenterica.

    PubMed

    Sakagami, Y; Yoshida, M; Isogai, A; Suzuki, A

    1981-06-26

    The pair of peptidal sex hormones (tremerogen A-10 and tremerogen a-13) that induce conjugation tube formation in compatible type cells (A and a types) of Tremella mesenterica were isolated. Tremerogen A-10 is a dodecapeptide and tremerogen a-13, a tridecapeptide. In both peptides, the sulfiydryl group of the cysteines at the carboxyl terminus was blocked by farnesyl moieties.

  18. [Study on exogenous hormones inducing parthenocarpy fruit growth and development and quality of Siraitia grosvenorii].

    PubMed

    Huang, Jie; Tu, Dong-ping; Ma, Xiao-jun; Mo, Chang-ming; Pan, Li-mei; Bai, Long-hua; Feng, Shi-xin

    2015-09-01

    To explore the growth and development and analyze the quality of the parthenocarpy fruit induced by exogenous hormones of Siraitia grosvenorii. the horizontal and vertical diameter, volume of the fruit were respectively measured by morphological and the content of endogenous hormones were determined by ELISA. The size and seed and content of mogrosides of mature fruit were determined. The results showed that the fruit of parthenocarpy was seedless and its growth and development is similar to the diploid fruit by hand pollination and triploid fruit by hand pollination or hormones. But the absolute value of horizontal and vertical diameter, volume of parthenocarpy fruit was less than those of fruit by hand pollination, while triploid was opposite. The content of IAA, ABA and ratio of ABA/GA was obviously wavy. At 0-30 d the content of IAA and ABA of parthenocarpy fruit first reduced then increased, content of IAA and GA parthenocarpy fruit was higher than that of fruit by hand pollination. Mogrosides of parthenocarpy fruit was close to pollination fruit. Hormones can induce S. grosvenorii parthenocarpy to get seedless fruit and the fruit shape and size and quality is close to normal diploid fruit by hand pollination and better than triploid fruit by hormone or hand pollination.

  19. Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone

    SciTech Connect

    Paz-Bouza, J.I.; Redding, T.W.; Schally, A.V.

    1987-02-01

    Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog (RC-160) or with (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) delayed delivery systems. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with (D-Trp/sub 2/)LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with (D-Trp/sup 6/)LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend the authors findings, obtained in male animals with transplanted tumors, that (D-Trp/sub 6/)LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.

  20. [Molecular-cellular and hormonal mechanisms of induced brain tolerance of extreme factors].

    PubMed

    Samoĭlov, M O; Rybnikova, E A

    2012-01-01

    This review includes results of own studies and literature data on the topical problem of neurobiology and medicine: discovery of the mechanisms of increased brain resistance to extreme exposures. The emphasis is made on the molecular-cellular and hormonal mechanisms of hypoxic preconditioning-induced brain tolerance to injurious hypoxia, psychoemotional and traumatic stress. A role of basic hormonal and intracellular cascade pro-adaptive processes mediating the neuroprotective action of hypoxic preconditioning is reviewed. A dynamics of the mechanisms of development of induced susceptible brain areas (hippocampus, neocortex) tolerance which includes phases of induction, transformation and expression, is presented. New data on preconditioning-induced cross-tolerance providing increased brain resistance not only to hypoxia but also to other stresses are reported. For the first time neuroprotective effects of hypoxic postconditioning are described.

  1. A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes.

    PubMed

    Valsangkar, Deepa; Downs, Stephen M

    2013-08-01

    We have previously shown that fatty acid oxidation (FAO) is required for AMP-activated protein kinase (PRKA)-induced maturation in vitro. In the present study, we have further investigated the role of this metabolic pathway in hormone-induced meiotic maturation. Incorporating an assay with (3)H-palmitic acid as the substrate, we first examined the effect of PRKA activators on FAO levels. There was a significant stimulation of FAO in cumulus cell-enclosed oocytes (CEO) treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and RSVA405. In denuded oocytes (DO), AICAR stimulated FAO only in the presence of carnitine, the molecule that facilitates fatty acyl CoA entry into the mitochondria. The carnitine palmitoyltransferase 1 activator C75 successfully stimulated FAO in CEO. All three of these activators trigger germinal vesicle breakdown. Meiotic resumption induced by follicle-stimulating hormone (FSH) or amphiregulin was completely inhibited by the FAO inhibitors etomoxir, mercaptoacetate, and malonyl CoA. Importantly, FAO was increased in CEO stimulated by FSH and epidermal growth factor, and this increase was blocked by FAO inhibitors. Moreover, compound C, a PRKA inhibitor, prevented the FSH-induced increase in FAO. Both carnitine and palmitic acid augmented hormonal induction of maturation. In a more physiological setting, etomoxir eliminated human chorionic gonadotropin (hCG)-induced maturation in follicle-enclosed oocytes. In addition, CEO and DO from hCG-treated mice displayed an etomoxir-sensitive increase in FAO, indicating that this pathway was stimulated during in vivo meiotic resumption. Taken together, our data indicate that hormone-induced maturation in mice requires a PRKA-dependent increase in FAO.

  2. A histological investigation of the maturation of the acorn worm, an inhabitant of the Sea of Japan, and a suggestion about the relationship between synchronized spawning/spermiation and the tidal level.

    PubMed

    Ogiso, Shouzo; Sakai, Kei-ichi; Matada, Masahiro; Sasayama, Yuichi

    2005-05-01

    One species of Hemichordata, Balanoglossus misakiensis, is then acorn worm originally reported from the intertidal zone of the Miura Peninsula on the Pacific Ocean side of Japan. We histologically examined the reproductive cycle of the population of this species, which inhabits only the sublittoral zone in the Sea of Japan. Testes and ovaries began to develop at the beginning of May 2003 and were almost mature in the latter half of June in males and in the first half of July in females in the same year. Subsequently, spermiation and spawning followed in the latter half of July in males and in the first half of August in females. Progress in maturation appeared to be related to increases in the water temperature. Although some experiments were conducted in aquariums to identify the conditions responsible for the synchronization of the occurrence of spontaneous spawning/spermiation, no clues were obtained. During the experiments, however, 11, 2, and 4 individuals out of the 67 used achieved spawning/spermiation on separate days. The occurrence of spawning/spermiation in the laboratory corresponded to the latter half of the switch from high tide to low tide on those days. Also in the field, it was known that they released the gametes according to this specific schedule. Therefore, it was suggested that, in the Japan Sea population of this species, the tide level may be a condition for synchronized spawning/spermiation.

  3. Early thyroid hormone-induced gene expression changes in N2a-β neuroblastoma cells.

    PubMed

    Bedó, Gabriela; Pascual, Angel; Aranda, Ana

    2011-10-01

    Thyroid hormone has long been known to regulate neural development. Hypothyroidism during pregnancy and early postnatal period has severe neurological consequences including even mental retardation. The purpose of this study was to characterize gene expression pattern during thyroid hormone-induced differentiation of neuro-2a β cells in order to select "direct response genes" for further analysis. In this neuroblastoma cell line, thyroid hormone blocks proliferation and induces differentiation. Changes in gene expression level were examined after a T3 treatment of 3 and 24 h using cDNA arrays. Sixteen genes were significantly up-regulated and 79 down-regulated by T3 treatment. Five up-regulated genes not previously described as regulated by thyroid hormone and selected for their putative significance to understand T3 action on cell differentiation, were verified by RT-PCR analysis. The transcription factors Phox2a and basic helix-loop-helix domain containing, class B2 mRNAs exhibited a clear increase after 3- and 24-h treatment. The guanine-nucleotide exchange factor RalGDS was greatly up-regulated after 3-h treatment but not 24 h after. The results suggest an early involvement of these genes in T3 action during neuroblastoma cell differentiation probably mediating later changes in gene expression pattern.

  4. Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato

    PubMed Central

    Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J.; Jung, Sabine C.; Pascual, Jose A.; Pozo, María J.

    2013-01-01

    Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Trichoderma ISR (TISR) is believed to involve a wider variety of signaling routes, interconnected in a complex network of cross-communicating hormone pathways. Using tomato as a model, an integrative analysis of the main mechanisms involved in the systemic resistance induced by Trichoderma harzianum against the necrotrophic leaf pathogen Botrytis cinerea was performed. Root colonization by T. harzianum rendered the leaves more resistant to B. cinerea independently of major effects on plant nutrition. The analysis of disease development in shoots of tomato mutant lines impaired in the synthesis of the key defense-related hormones JA, ET, salicylic acid (SA), and abscisic acid (ABA), and the peptide prosystemin (PS) evidenced the requirement of intact JA, SA, and ABA signaling pathways for a functional TISR. Expression analysis of several hormone-related marker genes point to the role of priming for enhanced JA-dependent defense responses upon pathogen infection. Together, our results indicate that although TISR induced in tomato against necrotrophs is mainly based on boosted JA-dependent responses, the pathways regulated by the plant hormones SA- and ABA are also required for successful TISR development. PMID:23805146

  5. Deciphering the hormonal signalling network behind the systemic resistance induced by Trichoderma harzianum in tomato.

    PubMed

    Martínez-Medina, Ainhoa; Fernández, Iván; Sánchez-Guzmán, María J; Jung, Sabine C; Pascual, Jose A; Pozo, María J

    2013-01-01

    Root colonization by selected Trichoderma isolates can activate in the plant a systemic defense response that is effective against a broad-spectrum of plant pathogens. Diverse plant hormones play pivotal roles in the regulation of the defense signaling network that leads to the induction of systemic resistance triggered by beneficial organisms [induced systemic resistance (ISR)]. Among them, jasmonic acid (JA) and ethylene (ET) signaling pathways are generally essential for ISR. However, Trichoderma ISR (TISR) is believed to involve a wider variety of signaling routes, interconnected in a complex network of cross-communicating hormone pathways. Using tomato as a model, an integrative analysis of the main mechanisms involved in the systemic resistance induced by Trichoderma harzianum against the necrotrophic leaf pathogen Botrytis cinerea was performed. Root colonization by T. harzianum rendered the leaves more resistant to B. cinerea independently of major effects on plant nutrition. The analysis of disease development in shoots of tomato mutant lines impaired in the synthesis of the key defense-related hormones JA, ET, salicylic acid (SA), and abscisic acid (ABA), and the peptide prosystemin (PS) evidenced the requirement of intact JA, SA, and ABA signaling pathways for a functional TISR. Expression analysis of several hormone-related marker genes point to the role of priming for enhanced JA-dependent defense responses upon pathogen infection. Together, our results indicate that although TISR induced in tomato against necrotrophs is mainly based on boosted JA-dependent responses, the pathways regulated by the plant hormones SA- and ABA are also required for successful TISR development.

  6. New approaches to male non-hormonal contraception.

    PubMed

    Nya-Ngatchou, Jean-Jacques; Amory, John K

    2013-03-01

    A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials.

  7. Effects of alprazolam on increases in hormonal and anxiety levels induced by meta-chlorophenylpiperazine.

    PubMed

    Sevy, S; Brown, S L; Wetzler, S; Kotler, M; Molcho, A; Plutchik, R; van Praag, H M

    1994-09-01

    The effects of alprazolam, a triazolobenzodiazepine, on hormonal and behavioral responses induced by meta-chlorophenylpiperazine (MCPP), a serotonin receptor agonist, were investigated in 10 healthy men. Alprazolam (0.5 mg) or placebo was given 1 hour before MCPP (0.5 mg/kg) or placebo. Cortisol, prolactin, and growth hormone (GH) release, MCPP and alprazolam plasma levels, anxiety level, and panic symptoms were measured over 210 minutes. MCPP was found to increase cortisol, prolactin, GH, and anxiety levels. Alprazolam decreased cortisol and GH levels but had no effect on prolactin. When used in combination with MCPP, alprazolam blunted MCPP-induced cortisol and GH release, and it blocked the anxiogenic effects of MCPP.

  8. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear

    PubMed Central

    Meyer, Retsina M.; Burgos-Robles, Anthony; Liu, Elizabeth; Correia, Susana S.; Goosens, Ki A.

    2014-01-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is not a clear relationship between the levels of these hormones and stress-associated mental illnesses such as post-traumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin releasing factor (CRF) or corticosterone. Repeated intra-amygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was increased by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin

  9. Identification of two juvenile hormone inducible transcription factors from the silkworm, Bombyx mori.

    PubMed

    Matsumoto, Hitoshi; Ueno, Chihiro; Nakamura, Yuki; Kinjoh, Terunori; Ito, Yuka; Shimura, Sachiko; Noda, Hiroaki; Imanishi, Shigeo; Mita, Kazuei; Fujiwara, Haruhiko; Hiruma, Kiyoshi; Shinoda, Tetsuro; Kamimura, Manabu

    2015-09-01

    Juvenile hormone (JH) regulates many physiological processes in insects. However, the signal cascades in which JH is active have not yet been fully elucidated, particularly in comparison to another major hormone ecdysteroid. Here we identified two JH inducible transcription factors as candidate components of JH signaling pathways in the silkworm, Bombyx mori. DNA microarray analysis showed that expression of two transcription factor genes, E75 and Enhancer of split mβ (E(spl)mβ), was induced by juvenile hormone I (JH I) in NIAS-Bm-aff3 cells. Real time RT-PCR analysis confirmed that expression of four E75 isoforms (E75A, E75B, E75C and E75D) and E(spl)mβ was 3-8 times greater after JH I addition. Addition of the protein synthesis inhibitor cycloheximide did not suppress JH-induced expression of the genes, indicating that they were directly induced by JH. JH-induced expression of E75 and E(spl)mβ was also observed in four other B. mori cell lines and in larval hemocytes of final instar larvae. Notably, E75A expression was induced very strongly in larval hemocytes by topical application of the JH analog fenoxycarb; the level of induced expression was comparable to that produced by feeding larvae with 20-hydroxyecdysone. These results suggest that E75 and E(spl)mβ are general and direct target genes of JH and that the transcription factors encoded by these genes play important roles in JH signaling.

  10. Hormonal changes accompanying cigarette smoke-induced preterm births in a mouse model.

    PubMed

    Ng, Sheung P; Steinetz, Bernard G; Lasano, Salamia G; Zelikoff, Judith T

    2006-09-01

    Epidemiologic evidence indicates that maternal smoking increases the risk of preterm birth. While a number of plausible mechanisms for early delivery have been offered, the role of gestational hormones in this smoke-induced outcome is uncertain. Thus, a toxicologic study was performed to examine the effects and underlying hormonal mechanisms of mainstream cigarette smoke (MCS) exposure on gestational duration. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 hrs/day) from Gestational Day (GD) 4 to parturition. Smoke-induced effects on gestational length, interpubic ligament length, maternal hormone secretion patterns (estradiol-17beta, progesterone, prolactin, and relaxin), body weight gain, postimplantation loss, litter size, and offspring sex ratio were examined. Dams exposed to MCS at a concentration equivalent to smoking less than one pack of cigarettes/day (carbon monoxide = 25 parts per million, total suspended particulates = 16 mg/m3) demonstrated a significant (P < 0.05) shortening of gestational duration (compared with pregnant, air-exposed mice). In addition, MCS-exposed mice sacrificed on GD 18 had significantly (P < 0.05) increased interpubic ligament length, elevated serum estrogen levels, and a reduced progesterone to estradiol-17beta ratio (compared with air-exposed controls); levels of progesterone and prolactin were only modestly decreased and increased, respectively, in the MCS-exposed mice. Smoke exposure had no significant effects on maternal relaxin levels, body weight gain, postimplantation loss, litter size, or sex ratio. Results of this study demonstrate that inhalation exposure of pregnant mice to a low dose of MCS shortens gestation and alters hormone secretory patterns, which are important for maintaining pregnancy and inducing parturition. These findings support the view that pregnant women who smoke (even modestly) may be at increased risk for preterm birth, and that early delivery may be related (at least

  11. Immunophotoaffinity labeling of binders of 1-methyladenine, the oocyte maturation-inducing hormone of starfish.

    PubMed

    Toraya, Tetsuo; Kida, Tetsuo; Kuyama, Atsushi; Matsuda, Shinjiro; Tanaka, Seiichi; Komatsu, Yo; Tsurukai, Taro

    2017-02-04

    Starfish oocytes are arrested at the prophase stage of the first meiotic division in the ovary and resume meiosis by the stimulus of 1-methyladenine (1-MeAde), the oocyte maturation-inducing hormone of starfish. Putative 1-MeAde receptors on the oocyte surface have been suggested, but not yet been biochemically characterized. Immunophotoaffinity labeling, i.e., photoaffinity labeling combined with immunochemical detection, was attempted to detect unknown 1-MeAde binders including putative maturation-inducing hormone receptors in starfish oocytes. When the oocyte crude membrane fraction or its Triton X-100/EDTA extract was incubated with N(6)-[6-(5-azido-2-nitrobenzoyl)aminohexyl]carboxamidomethyl-1-methyladenine and then photo-irradiated, followed by western blotting with antibody that was raised against a 1-MeAde hapten, a single band with Mr of 47.5 K was detected. The band was lost when extract was heated at 100 °C. A similar 47.5 K band was detected in the crude membrane fraction of testis as well. Upon labeling with whole cells, this band was detected in immature and maturing oocytes, but only faintly in mature oocytes. As judged from these results, this 1-MeAde binder might be a possible candidate of the starfish maturation-inducing hormone receptors.

  12. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    PubMed

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  13. Morphological changes in Daphnia galeata induced by a crustacean terpenoid hormone and its analog.

    PubMed

    Oda, Shigeto; Kato, Yasuhiko; Watanabe, Hajime; Tatarazako, Norihisa; Iguchi, Taisen

    2011-01-01

    Terpenoid hormones in insects (i.e., juvenile hormones) have various effects on physiology, morphology, and behavior, producing a wide range of phenotypic variation. Recent studies have shown that sex determination in cladoceran crustaceans is under the strong control of a major terpenoid hormone of crustaceans, methyl farnesoatote (MF). It can be easily conceived that MF is also a major determinant of other traits in cladocerans. In the present study, morphological changes known as antipredatory responses in a cladoceran Daphnia galeata in response to exposure to MF and a juvenile hormone-mimicking pesticide, fenoxycarb, were investigated. Morphological change was studied using neonates less than 24 h old, exposed either to MF at the concentrations from 1.9 to 30 µg/L, or fenoxycarb at the concentrations from 13 to 200 ng/L, for 6 d. Animals developed a longer helmet at 1.9 µg/L of MF and 25 ng/L of fenoxycarb, and showed a concentration-dependent elongation. However, the tail spine was reduced in size in a concentration-dependent manner. Results of the present study not only give new insight into the mechanisms of inducible defenses in cladocerans, but also provide invaluable information to understand ecological and evolutionary consequences of endocrine disruption through the shift in biological interaction between predator and prey.

  14. Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation.

    PubMed

    Torres-Chávez, K E; Sanfins, J M; Clemente-Napimoga, J T; Pelegrini-Da-Silva, A; Parada, C A; Fischer, L; Tambeli, C H

    2012-02-01

    We have recently demonstrated that gonadal steroid hormones decrease formalin-induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones.

  15. Naringenin and 17beta-estradiol coadministration prevents hormone-induced human cancer cell growth.

    PubMed

    Bulzomi, Pamela; Bolli, Alessandro; Galluzzo, Paola; Leone, Stefano; Acconcia, Filippo; Marino, Maria

    2010-01-01

    Flavonoids have been described as health-promoting, disease-preventing dietary components. In vivo and in vitro experiments also support a protective effect of flavonoids to reduce the incidence of certain hormone-responsive cancers. In particular, our previous results indicate that the flavanone naringenin (Nar), decoupling estrogen receptor alpha (ERalpha) action mechanisms, drives cancer cells to apoptosis. Because these studies were conducted in the absence of the endogenous hormone 17beta-estradiol (E2), the physiological relevance of these findings is not clear. We investigate whether the antiproliferative Nar effect persists in the presence of physiological E2 concentration (i.e. 10 nM), using both ERalpha-transfected (HeLa cells) and ERalpha-containing (HepG2 cells) cancer cell lines. Ligand saturation experiments indicate that Nar decreases the binding of E2 to ERalpha without impairing the estrogen response element (ERE)-driven reporter plasmid activity. In contrast, Nar stimulation prevents E2-induced extracellular regulated kinases (ERK1/2) and AKT activation and still induces the activation of p38, the proapoptotic member of mitogen-activating protein kinase (MAPK) family. As a consequence, Nar stimulation impedes the E2-induced transcription of cyclin D1 promoter and reverts the E2-induced cell proliferation, driving cancer cell to apoptosis. Thus, these results suggest that coexposure to this low-affinity, low-potency ligand for ERalpha specifically antagonizes the E2-induced ERalpha-dependent rapid signals by reducing the effect of the endogenous hormone in promoting cellular proliferation. As a whole, these data indicate that Nar is an excellent candidate as a chemopreventive agent in E2-dependent cancers.

  16. Effect of thyroid hormone status and concomitant medication on statin induced adverse effects in hyperlipidemic patients.

    PubMed

    Berta, E; Harangi, M; Zsíros, N; Nagy, E V; Paragh, G; Bodor, M

    2014-06-01

    Statins are effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, adverse effects induced by statins are the major barrier of maximalizing cardiovascular risk reduction. Hypothyroidism and administration of drugs metabolized on the same cytochrome P450 (CYPP450) pathways where statin biotransformation occurs represent a significant risk factor for statin induced adverse effects including myopathy. Simvastatin, atorvastatin and lovastatin are metabolized by CYP3A4, fluvastatin by CYP2C9, while rosuvastatin by CYP2C9 and 2C19. We investigated the levels of the free thyroid hormones and CYP metabolism of concomitant medication in 101 hyperlipidemic patients (age 61.3 +/- 9.9 ys) with statin induced adverse effects including myopathy (56 cases; 55.4%), hepatopathy (39 cases; 38.6%) and gastrointestinal adverse effects (24 cases; 23.8%). Abnormal thyroid hormone levels were found in 5 patients (4.95%); clinical hypothyroidism in 2 and hyperthyroidism in 3 cases. 11 patients had a positive history for hypothyroidism (10.9%). Myopathy occured in one patient with hypothyroidism and two patients with hyperthyroidism. There were no significant differences in the TSH, fT4 and fT3 levels between patients with statin induced myopathy and patients with other types of adverse effects. 78 patients (77.2%) were administered drugs metabolized by CYP isoforms also used by statins (3A4: 66 cases (65.3%); 2C9: 67 cases (66.3%); 2C19: 54 cases (53.5%)). Patients with myopathy took significantly more drugs metabolized by CYP3A4 compared to patients with other types of adverse effects (p < 0.05). More myopathy cases were found in patients on simvastatin treatment (52% vs. 38%, ns.), while significantly less patients with myopathy were on fluvastatin treatment (13% vs. 33%, p < 0.05) compared to patients with other types of statin induced adverse effects. Both abnormal thyroid hormone status and administration of drugs metabolized by CYP

  17. FoxO1 deacetylation regulates thyroid hormone-induced transcription of key hepatic gluconeogenic genes.

    PubMed

    Singh, Brijesh Kumar; Sinha, Rohit Anthony; Zhou, Jin; Xie, Sherwin Ying; You, Seo-Hee; Gauthier, Karine; Yen, Paul Michael

    2013-10-18

    Hepatic gluconeogenesis is a concerted process that integrates transcriptional regulation with hormonal signals. A major regulator is thyroid hormone (TH), which acts through its nuclear receptor (TR) to induce the expression of the hepatic gluconeogenic genes, phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC). Forkhead transcription factor FoxO1 also is an important regulator of these genes; however, its functional interactions with TR are not known. Here, we report that TR-mediated transcriptional activation of PCK1 and G6PC in human hepatic cells and mouse liver was FoxO1-dependent and furthermore required FoxO1 deacetylation by the NAD(+)-dependent deacetylase, SirT1. siRNA knockdown of FoxO1 decreased, whereas overexpression of FoxO1 increased, TH-dependent transcriptional activation of PCK1 and G6PC in cultured hepatic cells. FoxO1 siRNA knockdown also decreased TH-mediated transcription in vivo. Additionally, TH was unable to induce FoxO1 deacetylation or hepatic PCK1 gene expression in TH receptor β-null (TRβ(-/-)) mice. Moreover, TH stimulated FoxO1 recruitment to the PCK1 and G6PC gene promoters in a SirT1-dependent manner. In summary, our results show that TH-dependent deacetylation of a second metabolically regulated transcription factor represents a novel mechanism for transcriptional integration of nuclear hormone action with cellular energy status.

  18. Gentamicin Induced Nephrotoxicity: The Role of Sex Hormones in Gonadectomized Male and Female Rats

    PubMed Central

    Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir; Moslemi, Fatemeh

    2016-01-01

    Background. Gentamicin (GM) induced nephrotoxicity may be sex hormones related. The effects of sex hormones on GM induced nephrotoxicity in gonadectomized rats were investigated. Methods. Ovariectomized rats received 0.25, 0.5, or 1 mg/kg/week of estradiol (ES) alone or accompanied with 10 mg/kg/week of progesterone (Pro) for two weeks followed by GM (100 mg/kg/day) for 9 days. Castrated rats were also treated with 10, 50, or 100 mg/kg/week of testosterone (TS) for two weeks and then received GM. In addition, a single castrated group received 0.25 mg/kg/week of ES plus GM. Results. GM increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and kidney tissue damage score (KTDS) (P < 0.05). TS had no effect on the serum levels of BUN and Cr and KTDS, while low dose of ES intensified these parameters in male (P < 0.05). ES (0.5 mg/kg) without Pro ameliorated KTDS in female (P < 0.05) while ES (1 mg/kg) with or without Pro exacerbated the BUN values and Cr values, KTDS, and body weight loss (P < 0.05). Conclusion. ES (0.5 mg/kg) without Pro ameliorated kidney damage induced by GM in female while neither TS nor ES had beneficial effect on nephrotoxicity induced by GM in male, although ES aggravated it. PMID:27213082

  19. Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells.

    PubMed

    Fabbri, Francesco; Amadori, Dino; Carloni, Silvia; Brigliadori, Giovanni; Tesei, Anna; Ulivi, Paola; Rosetti, Marco; Vannini, Ivan; Arienti, Chiara; Zoli, Wainer; Silvestrini, Rosella

    2008-11-01

    Studies performed in different experimental and clinical settings have shown that Docetaxel (Doc) is effective in a wide range of tumors and that it exerts its activity through multiple mechanisms of action. However, the sequence of events induced by Doc which leads to cell death is still not fully understood. Moreover, it is not completely clear how Doc induces mitotic catastrophe and whether this process is an end event or followed by apoptosis or necrosis. We investigated the mechanisms by which Doc triggers cell death in hormone-refractory prostate cancer cells by analyzing cell cycle perturbations, apoptosis-related marker expression, and morphologic cell alterations. Doc induced a transient increase in G2/M phase followed by the appearance of G0/1 hypo- and hyperdiploid cells and increased p21 expression. Time- and concentration-dependent apoptosis was induced in up to 70% of cells, in concomitance with Bcl-2 phosphorylation, which was followed by caspase-2 and -3 activation. In conclusion, Doc would seem to trigger apoptosis in hormone-refractory prostate cancer cells via mitotic catastrophe through two forms of mitotic exit, in concomitance with increased p21 expression and caspase-2 activation.

  20. Hormonal control of germ cell development and spermatogenesis.

    PubMed

    O'Shaughnessy, Peter J

    2014-05-01

    Spermatogenesis is completely dependent on the pituitary hormone follicle-stimulating hormone (FSH) and androgens locally produced in response to luteinising hormone (LH). This dual control has been known since the 1930s and 1940s but more recent work, particularly using transgenic mice, has allowed us to determine which parts of the spermatogenic pathway are regulated by each hormone. During the first spermatogenic cycle after puberty both FSH and androgen act to limit the massive wave of germ cell apoptosis which occurs at this time. The established role of FSH in all cycles is to increase spermatogonial and subsequent spermatocyte numbers with a likely effect also on spermiation. Mice lacking FSH or its receptor are fertile, albeit with reduced germ cell numbers, and so this hormone is not an essential regulator of spermatogenesis but acts to optimise germ cell production Androgens also appear to regulate spermatogonial proliferation but, crucially, they are also required to allow spermatocytes to complete meiosis and form spermatids. Animals lacking androgen receptors fail to generate post-meiotic germ cells, therefore, and are infertile. There is also strong evidence that androgens act to ensure appropriate spermiation of mature spermatids. Androgen regulation of spermatogenesis is dependent upon action on the Sertoli cell but recent studies have shown that androgenic stimulation of the peritubular myoid cells is also essential for normal germ cells development. While FSH or androgen alone will both stimulate germ cell development, together they act synergistically to maximise germ cell number. The other hormones/local factors which can regulate spermatogenesis include activins and estrogens although their role in normal physiological regulation of this process needs to be more clearly established. Regulation of spermatogenesis in primates appears to be similar to that in rodents although the role of FSH may be greater. While our knowledge of hormone function

  1. Syndrome of inappropriate antidiuretic hormone-induced hyponatremia associated with amiodarone.

    PubMed

    Patel, Gourang P; Kasiar, Jennifer B

    2002-05-01

    The syndrome of inappropriate antidiuretic hormone (SIADH), the most common cause of euvolemic hyponatremia, is due to nonphysiologic release of arginine vasopressin from the posterior pituitary. Hyponatremia induced by SIADH can be caused by several conditions, such as central nervous system disorders, malignancies, various nonmalignant lung diseases, hypoadrenalism, and hypothyroidism. A 67-year-old man developed hyponatremia consistent with SIADH. Although common comorbid conditions associated with SIADH were excluded as possible causes, his medical history and drug regimen were extensive. However, he had been taking spironolactone, amiodarone, and simvastatin for less than 3 months. Amiodarone was discontinued based on a case report suggesting that this drug can cause SIADH-induced hyponatremia. The patient's serum sodium level began to rise within 3 days of discontinuation and returned to normal within 1 month. Although SIADH-induced hyponatremia occurs only rarely, it should be recognized as a possible adverse effect of amiodarone.

  2. Selenite-induced hormonal and signalling mechanisms during root growth of Arabidopsis thaliana L.

    PubMed

    Lehotai, Nóra; Kolbert, Zsuzsanna; Peto, Andrea; Feigl, Gábor; Ördög, Attila; Kumar, Devanand; Tari, Irma; Erdei, László

    2012-09-01

    Selenium excess can cause toxicity symptoms, e.g. root growth inhibition in non-hyperaccumulator plants such as Arabidopsis. Selenite-induced hormonal and signalling mechanisms in the course of development are poorly understood; therefore this study set out to investigate the possible hormonal and signalling processes using transgenic and mutant Arabidopsis plants. Significant alterations were observed in the root architecture of the selenite-treated plants, due to the loss of cell viability in the root apex. During mild selenite excess, the plants showed symptoms of the morphogenic response: primary root (PR) shortening and increased initiation of laterals, ensuring better nutrient and water uptake and stress acclimation. As well as lower meristem cell activity, the second reason for the Se-induced growth hindrance is the hormonal imbalance, since the in situ expression of the auxin-responsive DR5::GUS, and consequently the auxin levels, significantly decreased, while that of the cytokinin-inducible ARR5::GUS and the ethylene biosynthetic ACS8::GUS increased. It is assumed that auxin and ethylene might positively regulate selenium tolerance, since reduced levels of them resulted in sensitivity. Moreover, high cytokinin levels caused notable selenite tolerance. During early seedling development, nitric oxide (NO) contents decreased but hydrogen peroxide levels increased reflecting the antagonism between the two signal molecules during Se excess. High levels of NO in gsnor1-3, lead to selenite tolerance, while low NO production in nia1nia2 resulted in selenite sensitivity. Consequently, NO derived from the root nitrate reductase activity is responsible for the large-scale selenite tolerance in Arabidopsis.

  3. The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones.

    PubMed

    Panda, Sunanda

    2008-12-01

    An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract.

  4. A Case Report of Syndrome of Inappropriate Antidiuretic Hormone Induced by Pregabalin.

    PubMed

    Jung, Youn Joo; Lee, Dong-Young; Kim, Hae Won; Park, Hyun Sun; Kim, Beom

    2016-12-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hyponatremia, and many medications have been associated with SIADH. Pregabalin is a drug used for the treatment of neuropathic pain, though common adverse effects include central nervous system disturbance, peripheral edema, and weight gain. However, hyponatremia caused by pregabalin has been rarely reported. Here we report a patient with pregabalin-induced hyponatremia who met the criteria for SIADH; after discontinuation of the drug, his condition rapidly improved. This case can help clinicians diagnose and treat new-onset hyponatremia in patients who recently initiated pregabalin therapy.

  5. A Case Report of Syndrome of Inappropriate Antidiuretic Hormone Induced by Pregabalin

    PubMed Central

    Jung, Youn Joo; Lee, Dong-Young; Kim, Hae Won; Park, Hyun Sun

    2016-01-01

    The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hyponatremia, and many medications have been associated with SIADH. Pregabalin is a drug used for the treatment of neuropathic pain, though common adverse effects include central nervous system disturbance, peripheral edema, and weight gain. However, hyponatremia caused by pregabalin has been rarely reported. Here we report a patient with pregabalin-induced hyponatremia who met the criteria for SIADH; after discontinuation of the drug, his condition rapidly improved. This case can help clinicians diagnose and treat new-onset hyponatremia in patients who recently initiated pregabalin therapy. PMID:28275386

  6. Parathyroid hormone induces the Nrna family of nuclear orphan receptors in vivo

    SciTech Connect

    Pirih, Flavia Q. . E-mail: fqpirih@ucla.edu; Aghaloo, Tara L. . E-mail: taghaloo@ucla.edu; Bezouglaia, Olga . E-mail: obezougl@ucla.edu; Nervina, Jeanne M. . E-mail: jnervina@ucla.edu; Tetradis, Sotirios; E-mail: sotirist@dent.ucla.edu

    2005-07-01

    Parathyroid hormone (PTH) has both anabolic and catabolic effects on bone metabolism, although the molecular mechanisms mediating these effects are largely unknown. Among the transcription factors induced by Pth in osteoblasts are the nerve growth factor-inducible factor B (NR4A; NGFI-B) family of orphan nuclear receptors: Nurr1, Nur77, and NOR-1. PTH induces NR4A members through the cAMP-protein kinase A (PKA) pathway in vitro. We report here that PTH rapidly and transiently induced expression of all three NR4A genes in PTH-target tissues in vivo. In calvaria, long bones, and kidneys, NR4A induction was maximal 0.5-1 h after a single intraperitoneal (i.p.) injection of 80 {mu}g/kg PTH. Nur77 demonstrated the highest expression, followed, in order, by Nurr1 and NOR-1. In calvaria and long bone, PTH-induced expression of each NR4A gene was detectable at 10 {mu}g/kg i.p. with maximum induction at 40-80 {mu}g/kg. PTH (3-34) did not induce NR4A mRNA levels in calvaria, long bone, and kidney in vivo, confirming our in vitro results that NR4A genes are induced primarily through the cAMP-PKA pathway. The magnitude of PTH-induced NR4A expression was comparable in vivo and in vitro. However, NR4A mRNA levels peaked and returned to baseline faster in vivo. Both in vivo and in vitro, PTH induced NR4A pre-mRNA levels suggesting that induction of these genes is, at least in part, through activation of mRNA synthesis. The in vivo induction of the NR4A family members by PTH suggests their involvement in, at least some, PTH-induced changes in bone metabolism.

  7. Osteocalcin induces growth hormone/insulin-like growth factor-1 system by promoting testosterone synthesis in male mice.

    PubMed

    Li, Y; Li, K

    2014-10-01

    Osteocalcin has been shown to enhance testosterone production in men. In the present study, we investigated the effects of osteocalcin on testosterone and on induction of the growth hormone/insulin-like growth factor-1 axis. Osteocalcin injection stimulated growth, which could be inhibited by castration. In addition, osteocalcin induced testosterone secretion in testes both in vivo and in vitro. Using real-time polymerase chain reaction and Western blotting, we showed that growth hormone expression was significantly increased in the pituitary after osteocalcin injection (p<0.05). Growth hormone expression in CLU401 mouse pituitary cells was also significantly stimulated (p<0.05) by osteocalcin-induced MA-10 cells. Osteocalcin injection also promoted hepatic expression of growth hormone receptor and insulin-like growth factor-1 (p<0.05), as demonstrated by real-time polymerase chain reaction and Western blotting. Similarly, osteocalcin-induced MA-10 cells promoted growth hormone receptor and insulin-like growth factor-1 expression in NCTC1469 cells. These results suggest that the growth-stimulating activities of osteocalcin are mediated by testicular testosterone secretion, and thus provide valuable information regarding the regulatory effects of osteocalcin expression on the growth hormone/insulin-like growth factor-1 axis via reproductive activities.

  8. Growth hormone secretagogue receptor deficiency in mice protects against obesity‐induced hypertension

    PubMed Central

    Harris, Louise E.; Morgan, David G.; Balthasar, Nina

    2014-01-01

    Abstract Growth hormone secretagogue receptor (GHS‐R) signaling has been associated with growth hormone release, increases in food intake and pleiotropic cardiovascular effects. Recent data demonstrated that acute GHS‐R antagonism leads to increases in mean arterial pressure mediated by the sympathetic nervous system in rats; a highly undesirable effect if GHS‐R antagonism was to be used as a therapeutic approach to reducing food intake in an already obese, hypertensive patient population. However, our data in conscious, freely moving GHS‐R deficient mice demonstrate that chronic absence of GHS‐R signaling is protective against obesity‐induced hypertension. GHS‐R deficiency leads to reduced systolic blood pressure variability (SBPV); in response to acute high‐fat diet (HFD)‐feeding, increases in the sympathetic control of SBPV are suppressed in GHS‐R KO mice. Our data further suggest that GHS‐R signaling dampens the immediate HFD‐mediated increase in spontaneous baroreflex sensitivity. In diet‐induced obesity, absence of GHS‐R signaling leads to reductions in obesity‐mediated hypertension and tachycardia. Collectively, our findings thus suggest that chronic blockade of GHS‐R signaling may not result in adverse cardiovascular effects in obesity. PMID:24760503

  9. [Effect of dexamethasone on indomethacin-induced gastric erosion formation upon duration of the hormonal action].

    PubMed

    Podvigina, T T; Morozova, O Iu; Bagaeva, T R; Filaretova, L P

    2009-07-01

    The aim of the study was to verify a dependence of dexamethasone effect on the gastric erosion formation upon duration of the hormonal action. Gastric erosions were induced by indometha cin (35 mg/kg, sc) in male rats after 24-hour fasting. The rats were given a single injection of dexamethasone at a dose of 1 mg/kg and they underwent the ulcerogenic stimulus (indomethacin) at va rious time points after the hormonal injection (1, 6, 12, 18, 24 hours as well as 3, 5, 7 days). The control rats were given dexamethasone vehicle. In 4 hours after indomethacin injection gastric erosions, corticosterone and blood glucose levels, as well as body and thymus weights were examined. The results obtained demonstrate a dependence ofdexamethasone effect on the gastric erosion formation upon duration of its action: dexamethasone attenuated or aggravated indomethacin-induced gastric erosions depending on the time of its injection. Gastroprotective action of dexamethasone was observed in the case of its injection 1, 6, and 12 hours before indomethacin. The further increase in the time interval caused transformation of gastroprotective action of dexamethasone against ulcerogenic effect. The data obtained suggest that a disturbance of carbohydrate regulation accompanied with the signs of catabolic effects of the glucocorticoid may be responsible for the ulcerogenic action of dexamethasone.

  10. Olanzapine-induced changes in glucose metabolism are independent of the melanin-concentrating hormone system.

    PubMed

    Girault, Elodie M; Toonen, Pim W; Eggels, Leslie; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, Andries

    2013-11-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. Chagnon et al. showed that the common allele rs7973796 of the prepro-melanin-concentrating hormone (PMCH) gene is associated with a greater body mass index in Ola-treated schizophrenic patients. As PMCH encodes for the orexigenic neuropeptide melanin-concentrating hormone (MCH), it was hypothesized that MCH is involved in Ola-induced metabolic changes. We have recently reported that the intragastric infusion of Ola results in hyperglycaemia and insulin resistance in male rats. In order to test in vivo the possible involvement of the PMCH gene in the pathogenesis of Ola side-effects, we administered Ola intragastrically in wild-type (WT) and PMCH knock-out (KO) rats. Our results show that glucose and corticosterone levels, as well as endogenous glucose production, are elevated by the infusion of Ola in both WT and KO animals. Thus, the lack of MCH does not seem to affect the acute effects of Ola on glucose metabolism. On the other hand, these effects might be obliterated by compensatory changes in other hypothalamic systems. In addition, possible modulatory effects of the MCH KO on the long term effects of Ola, i.e. increased adiposity, body weight gain, have not been investigated yet.

  11. Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones.

    PubMed

    Fleshner, Monika; Campisi, Jay; Amiri, Leila; Diamond, David M

    2004-10-01

    Heat-shock proteins (Hsp) play an important role in stress physiology. Exposure to a variety of stressors will induce intracellular Hsp72, and this induction is believed to be beneficial for cell survival. In contrast, Hsp72 released during stress (extracellular Hsp72; eHsp72) activates pro-inflammatory responses. Clearly, physical stressors such as heat, cold, H(2)O(2), intense exercise and tail shock will induce both intra- and extracellular Hsp72. The current study tested whether a psychological stressor, cat exposure, would also trigger this response. In addition, the potential role of adrenal hormones in the Hsp72 response was examined. Adult, male Sprague Dawley rats were either adrenalectomized (ADX) or sham operated. Ten days post-recovery, rats were exposed to either a cat with no physical contact or control procedures (n = 5-6/group) for 2 h. Levels of intracellular Hsp72 were measured in the brain (frontal cortex, hippocampus, hypothalamus, dorsal vagal complex) and pituitary (ELISA). Levels of eHsp72 (ELISA) and corticosterone (RIA) were measured from serum obtained at the end of the 2-h stress period. Rats that were exposed to a cat had elevated intracellular Hsp72 in hypothalamus and dorsal vagal complex, and elevated eHsp72 and corticosterone in serum. Both the intra- and extracellular Hsp72 responses were blocked or attenuated by ADX. This study demonstrates that cat exposure can stimulate the Hsp72 response and that adrenal hormones contribute to this response.

  12. Bisphenol A induces corticotropin-releasing hormone expression in the placental cells JEG-3.

    PubMed

    Huang, Hui; Tan, Wenjuan; Wang, C C; Leung, Lai K

    2012-11-01

    Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproduction. Placental corticotrophin-releasing hormone (CRH) is a peptide hormone which is involved in fetal development. Increased plasma CRH is associated with elevated risk of premature delivery. In the present study, we demonstrated that bisphenol A increased CRH mRNA expression in the placental JEG-3 cells at or above 25μM. Reporter gene assay also demonstrated that bisphenol A could induce CRH gene transactivity. Since cyclic AMP response element (CRE) is a major regulatory element located in CRH promoter, the sequence-specific binding activity was investigated by using electrophoretic mobility shift assay. Our data indicated that bisphenol A increased the CRE binding activity. Western analysis further illustrated that PKA could be the signal triggering the CRE binding and CRH gene transactivation. In summary, the present study demonstrated that bisphenol A could induce CRH expression in placental cells and the underlying signal transduction pathway was also described.

  13. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients

    PubMed Central

    2011-01-01

    Background In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. Methods To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route), we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol), pain (VAS and other pain questionnaires), andrological (Ageing Males' Symptoms Scale - AMS) and psychological (POMS, CES-D and SF-36) parameters were evaluated at baseline (T0) and after 3, 6 and 12 months (T3, T6, T12 respectively). Results The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID) progressively improved from T3 to T12 while the other pain parameters (VAS, Area%) remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. Conclusions In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management. PMID:21332999

  14. Parathyroid hormone 1-34 reduces dexamethasone-induced terminal differentiation in human articular chondrocytes.

    PubMed

    Chang, Ling-Hua; Wu, Shun-Cheng; Chen, Chung-Hwan; Wang, Gwo-Jaw; Chang, Je-Ken; Ho, Mei-Ling

    2016-08-10

    Intra-articular injection of dexamethasone (Dex) is occasionally used to relieve pain and inflammation in osteoarthritis (OA) patients. Dex induces terminal differentiation of chondrogenic mesenchymal stem cells in vitro and causes impaired longitudinal skeletal growth in vivo. Parathyroid hormone 1-34 (PTH 1-34) has been shown to reverse terminal differentiation of osteoarthritic articular chondrocytes. We hypothesized that Dex induces terminal differentiation of articular chondrocytes and that this effect can be mitigated by PTH 1-34 treatment. We tested the effect of Dex on terminal differentiation in human articular chondrocytes and further tested if PTH 1-34 reverses the effects. We found that Dex treatment downregulated chondrogenic-induced expressions of SOX-9, collagen type IIa1 (Col2a1), and aggrecan and reduced synthesis of cartilaginous matrix (Col2a1 and sulfated glycosaminoglycan) synthesis. Dex treatment upregulated chondrocyte hypertrophic markers of collagen type X and alkaline phosphatase at mRNA and protein levels, and it increased the cell size of articular chondrocytes and induced cell death. These results indicated that Dex induces terminal differentiation of articular chondrocytes. To test whether PTH 1-34 treatment reverses Dex-induced terminal differentiation of articular chondrocytes, PTH 1-34 was co-administered with Dex. Results showed that PTH 1-34 treatment reversed both changes of chondrogenic and hypertrophic markers in chondrocytes induced by Dex. PTH 1-34 also decreased Dex-induced cell death. PTH 1-34 treatment reduces Dex-induced terminal differentiation and apoptosis of articular chondrocytes, and PTH 1-34 treatment may protect articular cartilage from further damage when received Dex administration.

  15. Illness-induced changes in thyroid hormone metabolism: focus on the tissue level.

    PubMed

    Kwakkel, J; Fliers, E; Boelen, A

    2011-05-01

    During illness changes in thyroid hormone metabolism occur, collectively known as the non-thyroidal illness syndrome (NTIS). NTIS is characterised by low serum thyroid hormone levels without the expected rise in serum thyroid-stimulating hormone, indicating a major change in thyroid hormone feedback regulation. Recent studies have made clear that during NTIS differential changes in thyroid hormone metabolism occur in various tissues, the net effect of which may be either activation or inhibition of thyroid hormone action. In this review we discuss systemic and local changes in thyroid hormone metabolism during illness, highlighting their physiological implications in terms of disease course.

  16. Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma.

    PubMed

    Munabi, Naikhoba C O; Tan, Qian Kun; Garzon, Maria C; Behr, Gerald G; Shawber, Carrie J; Wu, June K

    2015-01-01

    Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence.

  17. The adverse effects of high fat induced obesity on female reproductive cycle and hormones

    NASA Astrophysics Data System (ADS)

    Donthireddy, Laxminarasimha Reddy

    The prevalence of obesity, an established risk and progression factor for abnormal reproductive cycle and tissue damage in female mice. It leads to earlier puberty, menarche in young females and infertility. There are extensive range of consequences of obesity which includes type-2 diabetes, cardiovascular disease and insulin resistance. Obesity is the interaction between dietary intake, genes, life style and environment. The interplay of hormones estrogen, insulin, and leptin is well known on energy homeostasis and reproduction. The aim of this study is to determine the effect of high fat induced obesity on reproductive cycles and its hormonal abnormalities on mice model. Two week, 3 month and 8 month long normal (WT) and very high fat diet (VHFD) diet course is followed. When mice are fed with very high fat diet, there is a drastic increase in weight within the first week later. There was a significant (p<0.001) increase in leptin levels in 6 month VHFD treated animals. 2 week, 3 month and 6 month time interval pap smear test results showed number of cells, length of estrous cycle and phases of the estrous cycle changes with VHFD mice(n=30) compared to normal diet mice(n=10). These results also indicate that the changes in the reproductive cycles in VHFD treated female mice could be due to the changes in hormones. Histo-pathological analyses of kidney, ovary, liver, pancreas, heart and lungs showed remarkable changes in some tissue on exposure to very high fat. Highly deposited fat packets observed surrounding the hepatocytes and nerve cells.

  18. STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.

    PubMed

    Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi; Ren, Song-Guang; Wawrowsky, Kolja; Melmed, Shlomo

    2015-04-01

    Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.

  19. Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion*

    PubMed Central

    Yadav, Hariom; Lee, Ji-Hyeon; Lloyd, John; Walter, Peter; Rane, Sushil G.

    2013-01-01

    Obesity and diabetes are associated with excess caloric intake and reduced energy expenditure resulting in a negative energy balance. The incidence of diabetes has reached epidemic proportions, and childhood diabetes and obesity are increasing alarmingly. Therefore, it is important to develop safe, easily deliverable, and economically viable treatment alternatives for these diseases. Here, we provide data supporting the candidacy of probiotics as such a therapeutic modality against obesity and diabetes. Probiotics are live bacteria that colonize the gastrointestinal tract and impart beneficial effects for health. However, their widespread prescription as medical therapies is limited primarily because of the paucity of our understanding of their mechanism of action. Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action. These findings suggest that probiotics such as VSL#3 can modulate the gut microbiota-SCFA-hormone axis. Moreover, our results indicate that probiotics are of potential therapeutic utility to counter obesity and diabetes. PMID:23836895

  20. Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion.

    PubMed

    Yadav, Hariom; Lee, Ji-Hyeon; Lloyd, John; Walter, Peter; Rane, Sushil G

    2013-08-30

    Obesity and diabetes are associated with excess caloric intake and reduced energy expenditure resulting in a negative energy balance. The incidence of diabetes has reached epidemic proportions, and childhood diabetes and obesity are increasing alarmingly. Therefore, it is important to develop safe, easily deliverable, and economically viable treatment alternatives for these diseases. Here, we provide data supporting the candidacy of probiotics as such a therapeutic modality against obesity and diabetes. Probiotics are live bacteria that colonize the gastrointestinal tract and impart beneficial effects for health. However, their widespread prescription as medical therapies is limited primarily because of the paucity of our understanding of their mechanism of action. Here, we demonstrate that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models. VSL#3 suppressed body weight gain and insulin resistance via modulation of the gut flora composition. VSL#3 promoted the release of the hormone GLP-1, resulting in reduced food intake and improved glucose tolerance. The VSL#3-induced changes were associated with an increase in the levels of a short chain fatty acid (SCFA), butyrate. Using a cell culture system, we demonstrate that butyrate stimulated the release of GLP-1 from intestinal L-cells, thereby providing a plausible mechanism for VSL#3 action. These findings suggest that probiotics such as VSL#3 can modulate the gut microbiota-SCFA-hormone axis. Moreover, our results indicate that probiotics are of potential therapeutic utility to counter obesity and diabetes.

  1. Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression

    PubMed Central

    Li, Wen; Gan, Chen; Lv, Yue; Wang, Shanghu; Cheng, Huaidong

    2017-01-01

    Abstract This study aimed to investigate prospective memory impairment in patients with breast cancer with different expression of hormone receptors, including the estrogen receptor (ER) and the progesterone receptor (PR). A total of 120 patients with breast cancer who underwent chemotherapy following surgery were divided into 2 groups. The A group included 60 patients with ER−/PR− status, and the B group included 60 patients with ER+/PR+ status. After 6 cycles of postoperative adjuvant chemotherapy, all patients were administered neuropsychological and prospective memory tests, such as the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and digit span test (DST), as well as examination of event-based prospective memory (EBPM) and time-based prospective memory (TBPM). As the neuropsychological background test results showed, there were no significant differences in MMSE, DST, and TBPM scores (∗:P > 0.05) between patients with breast cancer in the ER−/PR− and ER+/PR+ groups, while the VFT and EBPM scores were significantly greater in patients with breast cancer with ER+/PR+ status than in those with ER−/PR− status (∗∗: P < 0.01), indicating that patients with ER−/PR− status have significant impairment in EBPM, although not in TBPM. The results of the present study indicate that different hormone receptor expression in patients with breast cancer may be associated with heterogeneity of chemotherapy-induced prospective memory impairment. PMID:28353608

  2. Cytoplasmic kinases downstream of GPR30 suppress gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone secretion from bovine anterior pituitary cells.

    PubMed

    Rudolf, Faidiban O; Kadokawa, Hiroya

    2016-01-01

    GPR30 is known as a membrane receptor for picomolar concentrations of estradiol. The GPR30-specific agonist G1 causes a rapid, non-genomic suppression of gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion from bovine anterior pituitary (AP) cells. A few studies have recently clarified that protein kinase A (PKA) and phosphorylated extracellular signal-regulated kinase (pERK) might be involved in cytoplasmic signaling pathways of GPR30 in other cells. Therefore, we tested the hypothesis that PKA and ERK kinase (MEK) are important cytoplasmic mediators for GPR30-associated non-genomic suppression of GnRH-induced LH secretion from bovine AP cells. Bovine AP cells (n = 8) were cultured for 3 days under steroid-free conditions. The AP cells were previously treated for 30 min with one of the following: 5000 nM of PKA inhibitor (H89), 1000 nM of MEK inhibitor (U0126), or a combination of H89 and U0126. Next, the AP cells were treated with 0.01 nM estradiol for 5 min before GnRH stimulation. Estradiol treatment without inhibitor pretreatment significantly suppressed GnRH-induced LH secretion (P < 0.01). In contrast, estradiol treatment after pretreatment with H89, U0126 or their combination had no suppressive effect on GnRH-induced LH secretion. The inhibitors also inhibited the G1 suppression of GnRH-induced LH secretion. Therefore, these data supported the hypothesis that PKA and MEK (thus, also pERK) are the intracellular mediators downstream of GPR30 that induce the non-genomic suppression of GnRH-induced LH secretion from bovine AP cells by estradiol or G1.

  3. Plasma levels of trace elements and exercise induced stress hormones in well-trained athletes.

    PubMed

    Soria, Marisol; González-Haro, Carlos; Ansón, Miguel; López-Colón, José L; Escanero, Jesús F

    2015-01-01

    This study analyzed the variation and relationship of several trace elements, metabolic substrates and stress hormones activated by exercise during incremental exercise. Seventeen well-trained endurance athletes performed a cycle ergometer test: after a warm-up of 10 min at 2.0 W kg(-1), the workload was increased by 0.5 W kg(-1) every 10 min until exhaustion. Prior diet, activity patterns, and levels of exercise training were controlled, and tests timed to minimize variations due to the circadian rhythm. Oxygen uptake, blood lactate concentration, plasma ions (Zn, Se, Mn and Co), serum glucose, non-esterified fatty acids (NEFAs) and several hormones were measured at rest, at the end of each stage and 3, 5 and 7 min post-exercise. Urine specific gravity was measured before and after the test, and participants drank water ad libitum. Significant differences were found in plasma Zn and Se levels as a function of exercise intensity. Zn was significantly correlated with epinephrine, norepinephrine and cortisol (r = 0.884, P < 0.01; r = 0.871, P < 0.01; and r = 0.808, P = 0.05); and Se showed significant positive correlations whit epinephrine and cortisol (r = 0.743, P < 0.05; and r = 0.776, P < 0.05). Neither Zn nor Se levels were associated with insulin or glucagon, and neither Mn nor Co levels were associated with any of the hormones or substrate metabolites studied. Further, while Zn levels were found to be associated only with lactate, plasma Se was significantly correlated with lactate and glucose (respectively for Zn: r = 0.891, P < 0.01; and for Se: r = 0.743, P < 0.05; r = 0.831, P < 0.05). In conclusion, our data suggest that there is a positive correlation between the increases in plasma Zn or Se and stress hormones variations induced by exercise along different submaximal intensities in well-hydrated well-trained endurance athletes.

  4. Nicotine decreases ethanol-induced dopamine signaling and increases self-administration via stress hormones.

    PubMed

    Doyon, William M; Dong, Yu; Ostroumov, Alexey; Thomas, Alyse M; Zhang, Tao A; Dani, John A

    2013-08-07

    Tobacco smoking is a well-known risk factor for subsequent alcohol abuse, but the neural events underlying this risk remain largely unknown. Alcohol and nicotine reinforcement involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to nicotine increases alcohol self-administration and decreases alcohol-induced dopamine responses. The blunted dopamine response was due to increased inhibitory synaptic transmission onto dopamine neurons. Blocking stress hormone receptors prior to nicotine exposure prevented all interactions with alcohol that we measured, including the increased inhibition onto dopamine neurons, the decreased dopamine responses, and the increased alcohol self-administration. These results indicate that nicotine recruits neuroendocrine systems to influence neurotransmission and behavior associated with alcohol reinforcement.

  5. Hormone-regulatable neoplastic transformation induced by a Jun-estrogen receptor chimera

    PubMed Central

    Kruse, Ulrich; Iacovoni, Jason S.; Goller, Martin E.; Vogt, Peter K.

    1997-01-01

    The v-jun oncogene encodes a nuclear DNA binding protein that functions as a transcription factor and is part of the activator protein 1 complex. Oncogenic transformation by v-jun is thought to be mediated by the aberrant expression of specific target genes. To identify such Jun-regulated genes and to explore the mechanisms by which Jun affects their expression, we have fused the full-length v-Jun and an amino-terminally truncated form of v-Jun to the hormone-binding domain of the human estrogen receptor. The two chimeric proteins function as ligand-inducible transactivators. Expression of the fusion proteins in chicken embryo fibroblasts causes estrogen-dependent transformation. PMID:9356460

  6. Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.

    PubMed

    Tarasiuk, A; Berdugo-Boura, N; Troib, A; Segev, Y

    2011-10-01

    Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p<0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p<0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p<0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.

  7. Cannabinoid CB1 receptor mediates glucocorticoid effects on hormone secretion induced by volume and osmotic changes.

    PubMed

    Ruginsk, S G; Uchoa, E T; Elias, L L K; Antunes-Rodrigues, J

    2012-02-01

    The present study provides the first in vivo evidence that the cannabinoid CB(1) receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB(1) receptor antagonist rimonabant (10 mg/Kg, p.o.), followed or not in 1 hour by dexamethasone (1 mg/Kg, i.p.). Extracellular volume expansion (EVE, 2 mL/100 g of body weight, i.v.) was performed 2 hours after dexamethasone or vehicle treatment using either isotonic (I-EVE, 0.15 mol/L) or hypertonic (H-EVE, 0.30 mol/L) NaCl solution. Five minutes after EVE, animals were decapitated and trunk blood was collected for all plasma measurements. Rimonabant potentiated oxytocin (OT) secretion induced by H-EVE and completely reversed the inhibitory effects of dexamethasone in response to the same stimulus. These data suggest that glucocorticoid modulation of OT release is mediated by the CB(1) receptor. Although dexamethasone did not affect vasopressin (AVP) secretion induced by H-EVE, the administration of rimonabant potentiated AVP release in response to the same stimulus, supporting the hypothesis that the CB(1) receptor regulates AVP secretion independently of glucocorticoid-mediated signalling. Dexamethasone alone did not affect atrial natriuretic peptide (ANP) release stimulated by I-EVE or H-EVE. However, pretreatment with rimonabant potentiated ANP secretion induced by H-EVE, suggesting a possible role for the CB(1) receptor in the control of peripheral factors that modulate cardiovascular function. Rimonabant also reversed the inhibitory effects of dexamethasone on H-EVE-induced corticosterone secretion, reinforcing the hypothesis that the CB(1) receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic-pituitary-adrenal axis. Collectively, the results of the present study indicate that the CB(1) receptor modulates neurohypophyseal hormone secretion and

  8. Neurodevelopmental Consequences of Low-Level Thyroid Hormone Disruption Induced by Environmental Contaminants

    EPA Science Inventory

    Inadequate levels of thyroid hormone during critical developmental periods lead to stunted growth, mental retardation, and neurological 'cretinism'. Animal models of developmental thyroid hormone deficiency mirror well the impact of severe insults to the thyroid system. However, ...

  9. GABAergic agents prevent alpha-melanocyte stimulating hormone induced anxiety and anorexia in rats.

    PubMed

    Rao, T Lakshmi; Kokare, Dadasaheb M; Sarkar, Sumit; Khisti, Rahul T; Chopde, Chandrabhan T; Subhedar, Nishikant

    2003-12-01

    Alpha-melanocyte stimulating hormone (alpha-MSH) is a hypothalamic peptide believed to play a tonic inhibitory role in feeding and energy homeostasis. Systemic administration of alpha-MSH is known to produce anorexia and anxiety. Since synaptic contacts between gamma-aminobutyric acid (GABA)ergic terminals and alpha-MSH neurons in the hypothalamus have been reported, the present work was undertaken to refine our knowledge on the role of GABAergic systems in anxiety and anorexia induced by intracerebroventricular (icv) administration of alpha-MSH in rats. The anxiety was assessed by elevated plus maze, and spontaneous food consumption was monitored during dark cycle. Prior administration of diazepam and muscimol that promote the function of GABA(A) receptors reversed the anxiogenic response and decreased food intake elicited by alpha-MSH. In contrast, bicuculline, the GABA(A) receptor antagonist, not only enhanced the effects of alpha-MSH but also prevented the influence of GABAergic drugs on alpha-MSH-induced anorexia and anxiety. These findings suggest that alpha-MSH-induced anxiety and anorexia are due to its negative influence on GABAergic system.

  10. Effects of mental resilience on neuroendocrine hormones level changes induced by sleep deprivation in servicemen.

    PubMed

    Sun, Xinyang; Dai, Xuyan; Yang, Tingshu; Song, Hongtao; Yang, Jialin; Bai, Jing; Zhang, Liyi

    2014-12-01

    The aim of this study was to investigate the effects of mental resilience on the changes of serum rennin, angiotensin, and cortisol level induced by sleep deprivation in servicemen. By random cluster sampling, a total of 160 servicemen, aged from 18 to 30, were selected to undergo 24-hour total sleep deprivation and administered the military personnel mental resilience scale after the deprivation procedure. The sleep deprivation procedure started at 8 a.m. on Day 8 and ended at 8 a.m. on Day 9 after 7 days of normal sleep for baseline preparation. Blood samples were drawn from the 160 participants at 8 a.m. respectively on Day 8 and Day 9 for hormonal measurements. All blood samples were analyzed using radioimmunoassay. As hypothesized, serum rennin, angiotensin II, and cortisol level of the participants after sleep deprivation were significantly higher than those before (P < 0.05). The changes of serum rennin and cortisol in the lower mental resilience subgroup were significantly greater (P < 0.05); problem-solving skill and willpower were the leading influence factors for the increases of serum rennin and cortisol respectively induced by sleep deprivation. We conclude that mental resilience plays a significant role in alleviating the changes of neurohormones level induced by sleep deprivation in servicemen.

  11. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  12. Epigenetic Upregulation of Corticotrophin-Releasing Hormone Mediates Postnatal Maternal Separation-Induced Memory Deficiency

    PubMed Central

    Wang, Aiyun; Nie, Wenying; Li, Haixia; Hou, Yuhua; Yu, Zhen; Fan, Qing; Sun, Ruopeng

    2014-01-01

    Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH) in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder. PMID:24718660

  13. Trichoderma harzianum and Glomus intraradices modify the hormone disruption induced by Fusarium oxysporum infection in melon plants.

    PubMed

    Martínez-Medina, Ainhoa; Pascual, Jose Antonio; Pérez-Alfocea, Francisco; Albacete, Alfonso; Roldán, Antonio

    2010-07-01

    The plant hormones salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA) are known to play crucial roles in plant disease and pest resistance. Changes in the concentrations of these plant hormones in melon plant shoots, as a consequence of the interaction between the plant, the pathogen Fusarium oxysporum, the antagonistic microorganism Trichoderma harzianum, and the arbuscular mycorrhizal fungus Glomus intraradices were investigated. Attack by F. oxysporum activated a defensive response in the plant, mediated by the plant hormones SA, JA, ET, and ABA, similar to the one produced by T. harzianum. When inoculated with the pathogen, both T. harzianum and G. intraradices attenuated the plant response mediated by the hormones ABA and ET elicited by the pathogen attack. T. harzianum was also able to attenuate the SA-mediated response. In the three-way interaction (F. oxysporum-T. harzianum-G. intraradices), although a synergistic effect in reducing disease incidence was found, no synergistic effect on the modulation of the hormone disruption induced by the pathogen was observed. These results suggest that the induction of plant basal resistance and the attenuation of the hormonal disruption caused by F. oxysporum are both mechanisms by which T. harzianum can control Fusarium wilt in melon plants; while the mechanisms involving G. intraradices seem to be independent of SA and JA signaling.

  14. Plant hormones increase efficiency of reprogramming mouse somatic cells to induced pluripotent stem cells and reduce tumorigenicity.

    PubMed

    Alvarez Palomo, Ana Belén; McLenachan, Samuel; Requena Osete, Jordi; Menchón, Cristina; Barrot, Carme; Chen, Fred; Munné-Bosch, Sergi; Edel, Michael J

    2014-03-15

    Reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined pluripotency and self-renewal factors has taken stem cell technology to the forefront of regenerative medicine. However, a number of challenges remain in the field including efficient protocols and the threat of cancer. Reprogramming of plant somatic cells to plant embryonic stem cells using a combination of two plant hormones was discovered in 1957 and has been a routine university laboratory practical for over 30 years. The plant hormones responsible for cell reprogramming to pluripotency, indole-3-acetic acid (IAA) and isopentenyl adenosine (IPA), are present in human cells, leading to the exciting possibility that plant hormones might reprogram mammalian cells without genetic factors. We found that plant hormones on their own could not reprogram mammalian cells but increase the efficiency of the early formation of iPS cells combined with three defined genetic factors during the first 3 weeks of reprogramming by accelerating the cell cycle and regulating pluripotency genes. Moreover, the cytokinin IPA, a known human anticancer agent, reduced the threat of cancer of iPS cell in vitro by regulating key cancer and stem cell-related genes, most notably c-Myc and Igf-1. In conclusion, the plant hormones, auxin and cytokinin, are new small chemicals useful for enhancing early reprogramming efficiency of mammalian cells and reducing the threat of cancer from iPS cells. These findings suggest a novel role for plant hormones in the biology of mammalian cell plasticity.

  15. Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period.

    PubMed

    Zhang, Mao; Zhan, Xiao L; Ma, Zi Y; Chen, Xing S; Cai, Qi Y; Yao, Zhong X

    2015-09-01

    Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS.

  16. Growth Hormone Induces Transforming Growth Factor-Beta-Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria.

    PubMed

    Chitra, P Swathi; Swathi, T; Sahay, Rakesh; Reddy, G Bhanuprakash; Menon, Ram K; Kumar, P Anil

    2015-09-01

    The glomerular podocytes form a major size selective barrier for the filtration of serum proteins and reduced podocyte number is a critical event in the pathogenesis of proteinuria during diabetic nephropathy (DN). An elevated level of growth hormone (GH) is implicated as a causative factor in the development of nephropathy in patients with type 1 diabetes mellitus. We have previously shown that podocytes express GH receptor and are a target for GH action. To elucidate the molecular basis for the effects of GH on podocyte depletion, we conducted PCR-array analyses for extracellular matrix and adhesion molecules in podocytes. Our studies reveal that GH increases expression of a gene that encodes transforming growth factor-beta-induced protein (TGFBIp) expression. Similarly, microarray data retrieved from the Nephromine database revealed elevation of TGFBIp in patients with DN. Treatment with GH results in increased secretion of extracellular TGFBIp by podocytes. Both GH and TGFBIp induced apoptosis and epithelial mesenchymal transition (EMT) of podocytes. Exposure of podocytes to GH and TGFBIp resulted in increased migration of cells and altered podocyte permeability to albumin across podocyte monolayer. Administration of GH to rats induced EMT and apoptosis in the glomerular fraction of the kidney. Therefore, we conclude that the GH-dependent increase in TGFBIp in the podocyte is one of the mechanisms responsible for podocyte depletion in DN.

  17. Monoclonal antibodies to human growth hormone induce an allosteric conformational change in the antigen.

    PubMed Central

    Mazza, M M; Retegui, L A

    1989-01-01

    We re-investigated the properties of a monoclonal antibody (mAb), 4D11, to human growth hormone (hGH) that showed a very weak affinity, recognizing hGH only when the hormone was solubilized on a solid surface. MAb4D11 did not significantly bind 125I-hGH. It was found that three mAb directed to different hGH epitopes (mAb 3C11, 10C1 and NA71) were able to induce the binding of the soluble antigen to mAb 4D11. The co-operative effect could be demonstrated by the formation of binary complexes (Ag:Ab, 1:2) detected by high-performance liquid chromatography (HPLC) and by the increase of radioactivity found when the synergistic mAb were added to 125I-hGH incubated with mAb 4D11 immobilized on polyvinyl microplates. Other possible explanations, such as the formation of cyclic complexes or the generation of a new epitope in the Fc fragment of the first antibody (Ab), were dismissed because the Fab fragment of one of the enhancing mAb (3C11) gave the same effect as the intact Ab. The data suggest that the hGH molecule undergoes a localized conformational change after binding to mAb 3C11, NA71 or 10C1 and that mAb 4D11 binds with high affinity to the modified region of the hormone. The formation or not of ternary complexes (Ag:Ab, 1:3) was used to localize the 4D11 epitope on the surface of the Ag. It is suggested that mAb 4D11 recognizes a conformational change produced in the region defined by the AE5/AC8 epitopes, which is close to the hGH antigenic domain only expressed when the protein is immobilized on plastic surfaces. PMID:2473953

  18. Muscle-specific growth hormone receptor (GHR) overexpression induces hyperplasia but not hypertrophy in transgenic zebrafish.

    PubMed

    Figueiredo, Marcio Azevedo; Mareco, Edson A; Silva, Maeli Dal Pai; Marins, Luis Fernando

    2012-06-01

    Even though growth hormone (GH) transgenesis has demonstrated potential for improved growth of commercially important species, the hormone excess may result in undesired collateral effects. In this context, the aim of this work was to develop a new model of transgenic zebrafish (Danio rerio) characterized by a muscle-specific overexpression of the GH receptor (GHR) gene, evaluating the effect of transgenesis on growth, muscle structure and expression of growth-related genes. In on line of transgenic zebrafish overexpressing GHR in skeletal muscle, no significant difference in total weight in comparison to non-transgenics was observed. This can be explained by a significant reduction in expression of somatotrophic axis-related genes, in special insulin-like growth factor I (IGF-I). In the same sense, a significant increase in expression of the suppressors of cytokine signaling 1 and 3 (SOCS) was encountered in transgenics. Surprisingly, expression of genes coding for the main myogenic regulatory factors (MRFs) was higher in transgenic than non-transgenic zebrafish. Genes coding for muscle proteins did not follow the MRFs profile, showing a significant decrease in their expression. These results were corroborated by the histological analysis, where a hyperplasic muscle growth was observed in transgenics. In conclusion, our results demonstrated that GHR overexpression does not induce hypertrophic muscle growth in transgenic zebrafish probably because of SOCS impairment of the GHR/IGF-I pathway, culminating in IGF-I and muscle proteins decrease. Therefore, it seems that hypertrophy and hyperplasia follow two different routes for entire muscle growth, both of them triggered by GHR activation, but regulated by different mechanisms.

  19. The thyroid hormone receptor β induces DNA damage and premature senescence

    PubMed Central

    Zambrano, Alberto; García-Carpizo, Verónica; Gallardo, María Esther; Villamuera, Raquel; Gómez-Ferrería, Maria Ana; Pascual, Angel; Buisine, Nicolas; Sachs, Laurent M.; Garesse, Rafael

    2014-01-01

    There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate–activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism. PMID:24395638

  20. PRC2 Represses Hormone-Induced Somatic Embryogenesis in Vegetative Tissue of Arabidopsis thaliana

    PubMed Central

    Mozgová, Iva

    2017-01-01

    Many plant cells can be reprogrammed into a pluripotent state that allows ectopic organ development. Inducing totipotent states to stimulate somatic embryo (SE) development is, however, challenging due to insufficient understanding of molecular barriers that prevent somatic cell dedifferentiation. Here we show that Polycomb repressive complex 2 (PRC2)-activity imposes a barrier to hormone-mediated transcriptional reprogramming towards somatic embryogenesis in vegetative tissue of Arabidopsis thaliana. We identify factors that enable SE development in PRC2-depleted shoot and root tissue and demonstrate that the establishment of embryogenic potential is marked by ectopic co-activation of crucial developmental regulators that specify shoot, root and embryo identity. Using inducible activation of PRC2 in PRC2-depleted cells, we demonstrate that transient reduction of PRC2 activity is sufficient for SE formation. We suggest that modulation of PRC2 activity in plant vegetative tissue combined with targeted activation of developmental pathways will open possibilities for novel approaches to cell reprogramming. PMID:28095419

  1. Acetyl-L-carnitine suppresses thyroid hormone-induced and spontaneous anuran tadpole tail shortening.

    PubMed

    Hanada, Hideki; Kobuchi, Hirotsugu; Yamamoto, Masanao; Kashiwagi, Keiko; Katsu, Kenjiro; Utsumi, Toshihiko; Kashiwagi, Akihiko; Sasaki, Junzo; Inoue, Masayasu; Utsumi, Kozo

    2013-02-01

    Mitochondrial membrane permeability transition (MPT) plays a crucial role in apoptotic tail shortening during anuran metamorphosis. L-carnitine is known to shuttle free fatty acids (FFAs) from the cytosol into mitochondria matrix for β-oxidation and energy production, and in a previous study we found that treatment with L-carnitine suppresses 3, 3', 5-triiodothyronine (T3 ) and FFA-induced MPT by reducing the level of FFAs. In the present study we focus on acetyl-L-carnitine, which is also involved in fatty acid oxidation, to determine its effect on T3 -induced tail regression in Rana rugosa tadpoles and spontaneous tail regression in Xenopus laevis tadpoles. The ladder-like DNA profile and increases in caspase-3 and caspase-9 indicative of apoptosis in the tails of T3 -treated tadpoles were found to be suppressed by the addition of acetyl-L-carnitine. Likewise, acetyl-L-carnitine was found to inhibit thyroid hormone regulated spontaneous metamorphosis in X. laevis tadpoles, accompanied by decreases in caspase and phospholipase A2 activity, as well as non-ladder-like DNA profiles. These findings support our previous conclusion that elevated levels of FFAs initiate MPT and activate the signaling pathway controlling apoptotic cell death in tadpole tails during anuran metamorphosis.

  2. A model of transcriptional and morphological changes during thyroid hormone-induced metamorphosis of the axolotl.

    PubMed

    Page, Robert B; Monaghan, James R; Walker, John A; Voss, S Randal

    2009-06-01

    Anuran (frog) metamorphosis has long-served as a model of how thyroid hormones regulate post-embryonic development in vertebrates. However, comparatively little is known about urodele (salamander) metamorphosis. We conducted a detailed time-course study of induced metamorphosis in the Mexican axolotl (Ambystoma mexicanum) that probed metamorphic changes in morphology and gene expression in the skin. Using morphometrics, quantitative PCR, histology, and in situ hybridization we demonstrate that the development of transcriptional markers is fundamental to the resolution of early metamorphic events in axolotls. We then use linear and piecewise linear models to identify a sequence of morphological and transcriptional changes that define larval to adult remodeling events throughout metamorphosis. In addition, we show that transcriptional biomarkers are expressed in specific larval and adult cell populations of the skin and that temporal changes in these biomarkers correlate with tissue remodeling. We compare our results with other studies of natural and induced metamorphosis in urodeles and highlight what appear to be conserved features between urodele and anuran metamorphosis.

  3. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug.

    PubMed

    Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A; Schense, Jason C

    2009-03-01

    Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH(1-34)), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH(1-34)). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.

  4. A model of transcriptional and morphological changes during thyroid hormone-induced metamorphosis of the axolotl

    PubMed Central

    Page, Robert B.; Monaghan, James R.; Walker, John A.; Voss, S. Randal

    2009-01-01

    Anuran (frog) metamorphosis has long-served as a model of how thyroid hormones regulate post-embryonic development in vertebrates. However, comparatively little is known about urodele (salamander) metamorphosis. We conducted a detailed time-course study of induced metamorphosis in the Mexican axolotl (Ambystoma mexicanum) that probed metamorphic changes in morphology and gene expression in the skin. Using morphometrics, quantitative PCR, histology, and in situ hybridization we demonstrate that the development of transcriptional markers is fundamental to the resolution of early metamorphic events in axolotls. We then use linear and piecewise linear models to identify a sequence of morphological and transcriptional changes that define larval to adult remodeling events throughout metamorphosis. In addition, we show that transcriptional biomarkers are expressed in specific larval and adult cell populations of the skin and that temporal changes in these biomarkers correlate with tissue remodeling. We compare our results with other studies of natural and induced metamorphosis in urodeles and highlight what appear to be conserved features between urodele and anuran metamorphosis. PMID:19275901

  5. Lipoprotein receptor-related protein 6 is required for parathyroid hormone-induced Sost suppression.

    PubMed

    Li, Changjun; Wang, Weishan; Xie, Liang; Luo, Xianghang; Cao, Xu; Wan, Mei

    2016-01-01

    Parathyroid hormone (PTH) suppresses the expression of the bone formation inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)-dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor-related protein 6 (LRP6) mediates the intracellular signaling activation and the anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6-KO) mouse model. An increased level of Sost mRNA expression was detected in femur tissue from LRP6-KO mice, compared to wild-type littermates. The number of osteocytes expressing sclerostin protein was also increased in bone tissue of LRP6-KO littermates, indicating a negative regulatory role of LRP6 on Sost/sclerostin. In wild-type littermates, intermittent PTH treatment significantly suppressed Sost mRNA expression in bone and the number of sclerostin(+) osteocytes, while the effect of PTH was much less significant in LRP6-KO mice. Additionally, PTH-induced downregulation of MEF2C and 2D, as well as HDAC changes in osteocytes, were abrogated in LRP6-KO mice. These data indicate that LRP6 is required for PTH suppression of Sost expression.

  6. Antipsychotic-induced insulin resistance and postprandial hormonal dysregulation independent of weight gain or psychiatric disease.

    PubMed

    Teff, Karen L; Rickels, Michael R; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

    2013-09-01

    Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior.

  7. Exercise training associated with estrogen therapy induced cardiovascular benefits after ovarian hormones deprivation.

    PubMed

    Flues, Karin; Paulini, Janaina; Brito, Sebastião; Sanches, Iris Callado; Consolim-Colombo, Fernanda; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2010-03-01

    Menopause is recognized as a period of increased risk for coronary heart disease. Although the benefits of exercise training in lowering cardiovascular risk factors are well established, the risks and benefits of hormone therapy have been questioned. The purpose of the present study was to investigate the effects of estrogen therapy (HT) associated or not with exercise training (ET) in autonomic cardiovascular control in ovariectomized (OVX) rats. Female rats were divided into: control, OVX, OVX+HT, OVX+ET and OVX+HT+ET. HT was performed using a 0.25mg 8-weeks sustained release pellet. Trained groups were submitted to an 8-week exercise training protocol on treadmill. Baroreflex sensitivity (BRS) was evaluated by heart rate responses to arterial pressure (AP) changes, and vagal and sympathetic tonus by pharmacological blockade. Ovariectomy induced an AP increase (123+/-2mmHg vs. 108+/-2mmHg), BRS impairment ( approximately 69%), sympathetic activation ( approximately 100%) and vagal tonus reduction ( approximately 77%) compared to controls. HT or ET normalized the changes in parasympathetic tonus. However, only the association HT+ET was able to promote normalization of AP, BRS and sympathetic tonus, as compared to controls. These results indicate that ET induces cardiovascular and autonomic benefits in OVX rats under HT, suggesting a positive role of this association in the management of cardiovascular risk factor in postmenopausal women.

  8. Antipsychotic-Induced Insulin Resistance and Postprandial Hormonal Dysregulation Independent of Weight Gain or Psychiatric Disease

    PubMed Central

    Teff, Karen L.; Rickels, Michael R.; Grudziak, Joanna; Fuller, Carissa; Nguyen, Huong-Lan; Rickels, Karl

    2013-01-01

    Atypical antipsychotic (AAP) medications that have revolutionized the treatment of mental illness have become stigmatized by metabolic side effects, including obesity and diabetes. It remains controversial whether the defects are treatment induced or disease related. Although the mechanisms underlying these metabolic defects are not understood, it is assumed that the initiating pathophysiology is weight gain, secondary to centrally mediated increases in appetite. To determine if the AAPs have detrimental metabolic effects independent of weight gain or psychiatric disease, we administered olanzapine, aripiprazole, or placebo for 9 days to healthy subjects (n = 10, each group) under controlled in-patient conditions while maintaining activity levels. Prior to and after the interventions, we conducted a meal challenge and a euglycemic-hyperinsulinemic clamp to evaluate insulin sensitivity and glucose disposal. We found that olanzapine, an AAP highly associated with weight gain, causes significant elevations in postprandial insulin, glucagon-like peptide 1 (GLP-1), and glucagon coincident with insulin resistance compared with placebo. Aripiprazole, an AAP considered metabolically sparing, induces insulin resistance but has no effect on postprandial hormones. Importantly, the metabolic changes occur in the absence of weight gain, increases in food intake and hunger, or psychiatric disease, suggesting that AAPs exert direct effects on tissues independent of mechanisms regulating eating behavior. PMID:23835329

  9. Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes.

    PubMed

    Dentice, Monica; Luongo, Cristina; Huang, Stephen; Ambrosio, Raffaele; Elefante, Antonia; Mirebeau-Prunier, Delphine; Zavacki, Ann Marie; Fenzi, Gianfranco; Grachtchouk, Marina; Hutchin, Mark; Dlugosz, Andrzej A; Bianco, Antonio C; Missero, Caterina; Larsen, P Reed; Salvatore, Domenico

    2007-09-04

    The Sonic hedgehog (Shh) pathway plays a critical role in hair follicle physiology and is constitutively active in basal cell carcinomas (BCCs), the most common human malignancy. Type 3 iodothyronine deiodinase (D3), the thyroid hormone-inactivating enzyme, is frequently expressed in proliferating and neoplastic cells, but its role in this context is unknown. Here we show that Shh, through Gli2, directly induces D3 in proliferating keratinocytes and in mouse and human BCCs. We demonstrate that Gli-induced D3 reduces intracellular active thyroid hormone, thus resulting in increased cyclin D1 and keratinocyte proliferation. D3 knockdown caused a 5-fold reduction in the growth of BCC xenografts in nude mice. Shh-induced thyroid hormone degradation via D3 synergizes with the Shh-mediated reduction of the type 2 deiodinase, the thyroxine-activating enzyme, and both effects are reversed by cAMP. This previously unrecognized functional cross-talk between Shh/Gli2 and thyroid hormone in keratinocytes is a pathway by which Shh produces its proliferative effects and offers a potential therapeutic approach to BCC.

  10. Gonadal hormone modulation of ∆(9)-tetrahydrocannabinol-induced antinociception and metabolism in female versus male rats.

    PubMed

    Craft, R M; Haas, A E; Wiley, J L; Yu, Z; Clowers, B H

    2017-01-01

    The gonadal hormones testosterone (T) in adult males and estradiol (E2) in adult females have been reported to modulate behavioral effects of ∆(9)-tetrahydrocannabinol (THC). This study determined whether activational effects of T and E2 are sex-specific, and whether hormones modulate production of the active metabolite 11-hydroxy-THC (11-OH-THC) and the inactive metabolite 11-nor-9-carboxy-THC (THC-COOH). Adult male and female rats were gonadectomized (GDX) and treated with nothing (0), T (10-mm Silastic capsule/100g body weight), or E2 (1-mm Silastic capsule/rat). Three weeks later, saline or the cytochrome P450 inhibitor proadifen (25mg/kg; to block THC metabolism and boost THC's effects) was injected i.p.; 1h later, vehicle or THC (3mg/kg females, 5mg/kg males) was injected i.p., and rats were tested for antinociceptive and motoric effects 15-240min post-injection. T did not consistently alter THC-induced antinociception in males, but decreased it in females (tail withdrawal test). Conversely, T decreased THC-induced catalepsy in males, but had no effect in females. E2 did not alter THC-induced antinociception in females, but enhanced it in males. The discrepant effects of T and E2 on males' and females' behavioral responses to THC suggests that sexual differentiation of THC sensitivity is not simply due to activational effects of hormones, but also occurs via organizational hormone or sex chromosome effects. Analysis of serum showed that proadifen increased THC levels, E2 increased 11-OH-THC in GDX males, and T decreased 11-OH-THC (and to a lesser extent, THC) in GDX females. Thus, hormone modulation of THC's behavioral effects is caused in part by hormone modulation of THC oxidation to its active metabolite. However, the fact that hormone modulation of metabolism did not alter THC sensitivity similarly on all behavioral measures within each sex suggests that other mechanisms also play a role in gonadal hormone modulation of THC sensitivity in adult rats.

  11. Wolbachia-induced paternal defect in Drosophila is likely by interaction with the juvenile hormone pathway.

    PubMed

    Liu, Chen; Wang, Jia-Lin; Zheng, Ya; Xiong, En-Juan; Li, Jing-Jing; Yuan, Lin-Ling; Yu, Xiao-Qiang; Wang, Yu-Feng

    2014-06-01

    Wolbachia are endosymbionts that infect many insect species. They can manipulate the host's reproduction to increase their own maternal transmission. Cytoplasmic incompatibility (CI) is one such manipulation, which is expressed as embryonic lethality when Wolbachia-infected males mate with uninfected females. However, matings between males and females carrying the same Wolbachia strain result in viable progeny. The molecular mechanisms of CI are currently not clear. We have previously reported that the gene Juvenile hormone-inducible protein 26 (JhI-26) exhibited the highest upregulation in the 3rd instar larval testes of Drosophila melanogaster when infected by Wolbachia. This is reminiscent of an interaction between Wolbachia and juvenile hormone (JH) pathway in flies. Considering that Jhamt gene encodes JH acid methyltransferase, a key regulatory enzyme of JH biosynthesis, and that methoprene-tolerant (Met) has been regarded as the best JH receptor candidate, we first compared the expression of Jhamt and Met between Wolbachia-infected and uninfected fly testes to investigate whether Wolbachia infection influence the JH signaling pathway. We found that the expressions of Jhamt and Met were significantly increased in the presence of Wolbachia, suggesting an interaction of Wolbachia with the JH signaling pathway. Then, we found that overexpression of JhI-26 in Wolbachia-free transgenic male flies caused paternal-effect lethality that mimics the defects associated with CI. JhI-26 overexpressing males resulted in significantly decrease in hatch rate. Surprisingly, Wolbachia-infected females could rescue the egg hatch. In addition, we showed that overexpression of JhI-26 caused upregulation of the male accessory gland protein (Acp) gene CG10433, but not vice versa. This result suggests that JhI-26 may function at the upstream of CG10433. Likewise, overexpression of CG10433 also resulted in paternal-effect lethality. Both JhI-26 and CG10433 overexpressing males

  12. Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats

    SciTech Connect

    Schally, A.V.; Paz-Bouza, J.I.; Schlosser, J.V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.

    1987-02-01

    Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist (D-Trp/sup 6/)LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist (D-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

  13. 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

  14. Relation between the testicular sperm assay and sex hormone level in patients with azoospermia induced by mumps

    PubMed Central

    Zhang, Shuiwen; An, Yulin; Li, Junguo; Guo, Junhong; Zhou, Guoping; Li, Jianhua; Xu, Ye

    2015-01-01

    This study aimed to investigate the relation between the testicular sperm assay (TESA) and sex hormone level or testicular volume in patients with azoospermia induced by mumps. Samples from 52 patients with mumps-induced azoospermia were subjected to TESA, and then the sperm activity was observed microscopically. The sex hormone level was detected with an electrochemical assay, and ultrasound was used to calculate the testicular volume. Of the 52 azoospermia patients, 38 were found to have active sperms through testicular sperm extraction from the opened testis; furthermore, the serum follicle-stimulating hormone (FSH) and luteinizing hormone levels were obviously higher in the non-sperm group than in the sperm group (P < 0.05). Moreover, the testicular volume was smaller in the non-sperm group than in the sperm group; however, there was no significant difference between the two groups (P > 0.05). With the FSH value as a standard, the quantity of sperms was found to be within two times of, or more than two-fold of the normal range. With the testicular volume as a standard, sperms were found in testes with a volume of > 6 mL or < 6 mL. The FSH value and the testicular volume were indicators of the ability of the TESA to obtain sperms. To allow the performance of intracytoplasmic sperm injection, all patients need to undergo TESA. PMID:26885123

  15. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    PubMed

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.

  16. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    SciTech Connect

    Clayton, P.E.; Shalet, S.M. )

    1991-02-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.

  17. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  18. Comparison of Ultraviolet Photodissociation and Collision Induced Dissociation of Adrenocorticotropic Hormone Peptides

    NASA Astrophysics Data System (ADS)

    Robotham, Scott A.; Brodbelt, Jennifer S.

    2015-09-01

    In an effort to better characterize the fragmentation pathways promoted by ultraviolet photoexcitation in comparison to collision induced dissociation (CID), six adrenocorticotropic hormone (ACTH) peptides in a range of charge states were subjected to 266 nm ultraviolet photodissociation (UVPD), 193 nm UVPD, and CID. Similar fragment ions and distributions were observed for 266 nm UVPD and 193 nm UVPD for all peptides investigated. While both UVPD and CID led to preferential cleavage of the Y-S bond for all ACTH peptides [except ACTH (1-39)], UVPD was far less dependent on charge state and location of basic sites for the production of C-terminal and N-terminal ions. For ACTH (1-16), ACTH (1-17), ACTH (1-24), and ACTH (1-39), changes in the distributions of fragment ion types ( a, b, c, x, y, z, and collectively N-terminal ions versus C-terminal ions) showed only minor changes upon UVPD for all charge states. In contrast, CID displayed significant changes in the fragment ion type distributions as a function of charge state, an outcome consistent with the dependence on the number and location of mobile protons that is not prominent for UVPD. Sequence coverages obtained by UVPD showed less dependence on charge state than those determined by CID, with the latter showing a consistent decrease in coverage as charge state increased.

  19. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    PubMed Central

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  20. Cortisol interferes with the estradiol-induced surge of luteinizing hormone in the ewe.

    PubMed

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Pierce, Bree N; Tilbrook, Alan J; Turner, Anne I; Karsch, Fred J

    2009-03-01

    Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was approximately 1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

  1. Syndrome of inappropriate antidiuretic hormone secretion: a story of duloxetine-induced hyponatraemia.

    PubMed

    Amoako, Adae Opoku; Brown, Carina; Riley, Timothy

    2015-04-24

    Hyponatraemia is the most commonly encountered electrolyte abnormality in clinical practice. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for nearly 60% of all hyponatraemias. Selective serotonin reuptake inhibitors (SSRIs) are well known to have side effects of SIADH. There have been few reported cases of serotonin norepinephrine reuptake inhibitors (SNRIs) causing SIADH-induced hyponatraemia. Duloxetine is one type of SNRI used to treat several conditions, including depression and diabetic neuropathy. We present a case of a 76-year-old woman with a history of fibromyalgia who had recently been prescribed duloxetine for her condition. On admission to the hospital, her sodium decreased to a low of 118 mmol/L. Evaluation for other causes of hyponatraemia yielded negative results. Duloxetine was discontinued and after 3 days the patient's sodium increased to 130 mmol/L. The purpose of this case report is to highlight the importance of having suspicion for rare but real side effects of medications such as duloxetine.

  2. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    PubMed Central

    2010-01-01

    Background Non-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH) could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha) levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin), which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance. PMID:20653983

  3. Photo-induced regeneration of hormones by electron transfer processes: Potential biological and medical consequences

    NASA Astrophysics Data System (ADS)

    Getoff, Nikola; Hartmann, Johannes; Schittl, Heike; Gerschpacher, Marion; Quint, Ruth Maria

    2011-08-01

    Based on the previous results concerning electron transfer processes in biological substances, it was of interest to investigate if hormone transients resulting by e.g. electron emission can be regenerated. The presented results prove for the first time that the hormone transients originating by the electron emission process can be successfully regenerated by the transfer of electrons from a potent electron donor, such as vitamin C (VitC). Investigations were performed using progesterone (PRG), testosterone (TES) and estrone (E1) as representatives of hormones. By irradiation with monochromatic UV light (λ=254 nm) in a media of 40% water and 60% ethanol, the degradation as well as the regeneration of the hormones was studied with each hormone individually and in the mixture with VitC as a function of the absorbed UV dose, using HPLC. Calculated from the obtained initial yields, the determined regeneration of PRG amounted to 52.7%, for TES to 58.6% and for E1 to 90.9%. The consumption of VitC was determined in the same way. The reported results concerning the regeneration of hormones by the transfer of electrons from an electron donor offer a new, promising method for the therapy with hormones. As a consequence of the regeneration of hormones, a decreased formation of carcinogenic metabolites is expected.

  4. Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.

    PubMed

    Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A

    2016-06-01

    Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.

  5. The corticotropin-releasing hormone test in normal short children: comparison of plasma adrenocorticotropin and cortisol responses to human corticotropin-releasing hormone and insulin-induced hypoglycemia.

    PubMed

    Goji, K

    1989-03-01

    The human corticotropin-releasing hormone (hCRH) tests were performed in twelve normal short children, and the responses of plasma ACTH and cortisol to iv administration of 1 micrograms/kg hCRH were compared with those to insulin-induced hypoglycemia. After administration of hCRH, the mean plasma ACTH level rose from a basal value of 3.3 +/- 0.4 pmol/l (mean +/- SEM) to a peak value of 9.2 +/- 0.8 pmol/l at 30 min, and the mean plasma cortisol level rose from a basal value of 231 +/- 25 nmol/l to a peak value of 546 +/- 30 nmol/l at 30 min. The ACTH response after insulin-induced hypoglycemia was greater than that after hCRH administration; the mean peak level (P less than 0.01), the percent maximum increment (P less than 0.01), and the area under the ACTH response curve (P less than 0.01) were all significantly greater after insulin-induced hypoglycemia than those after hCRH administration. Although the mean peak cortisol level after insulin-induced hypoglycemia was about 1.3-fold higher than that after hCRH administration (P less than 0.01), neither the percent maximum increment in plasma cortisol nor the area under the cortisol response curve after insulin-induced hypoglycemia was significantly different from that after hCRH administration. Consequently, the acute increases in plasma ACTH after the administration of 1 microgram/kg hCRH stimulated the adrenal gland to almost the same cortisol response as that obtained with a much greater increase in plasma ACTH after insulin-induced hypoglycemia. These results suggest that a plasma ACTH peak of 9-11 pmol/l produces near maximum acute stimulation of adrenal steroidogenesis.

  6. Levels of miRNA and Hormones in Thoracic Duct Lymph in Rats with Experimental Breast Cancer Induced by N-Methyl-N-Nitrosourea.

    PubMed

    Lykov, A P; Kabakov, A V; Kazakov, O V; Bondarenko, N A; Poveshchenko, O V; Raiter, T V; Poveshchenko, A F; Strunkin, D N; Konenkov, V I

    2017-01-01

    We studied hormone levels in the thoracic duct lymph and expression of miRNA involved in the pathogenesis of breast cancer induced in rats by intramammary injection of N-methyl-Nnitrosourea. The correlations between miRNA expression and hormone levels depended on the type of treatment.

  7. Effect of aging on GHRF-induced growth hormone release from anterior pituitary cells in primary culture

    SciTech Connect

    Spik, K.W.; Boyd, R.L.; Sonntag, W.E.

    1991-03-01

    Five criteria were developed to validate the primary cell culture model for comparison of GRF-induced release of growth hormone in pituitary tissue from aging animals. Pituitaries from young (5-mo), middle-aged (14-mo), and old (24-mo) male Fischer 344 rats were dispersed using either trypsin/trypsin inhibitor or dispase and compared with respect to the number of pituitary cells recovered, cell viability, 3H-leucine incorporation into total protein, time course for recovery of optimal response to GRF, and the dose-relationship for GRF-induced release of growth hormone 2, 4, and 6 days after dispersal. Results indicated that direct comparison of cellular responses between tissues from young, middle-aged, and old rats in primary cell culture is confounded by variations in time for recovery of optimal responses, the effects of the enzymes used for dispersal, and the methods used to express the data.

  8. Beneficial effects of growth hormone-releasing hormone agonists on rat INS-1 cells and on streptozotocin-induced NOD/SCID mice

    PubMed Central

    Zhang, Xianyang; Cui, Tengjiao; He, Jinlin; Wang, Haibo; Cai, Renzhi; Popovics, Petra; Vidaurre, Irving; Sha, Wei; Schmid, Janine; Ludwig, Barbara; Block, Norman L.; Bornstein, Stefan R.; Schally, Andrew V.

    2015-01-01

    Agonists of growth hormone-releasing hormone (GHRH) have been previously reported to promote growth, function, and engraftment of islet cells following transplantation. Here we evaluated recently synthesized GHRH agonists on the proliferation and biological functions of rat pancreatic β-cell line (INS-1) and islets. In vitro treatment of INS-1 cells with GHRH agonists increased cell proliferation, the expression of cellular insulin, insulin-like growth factor-1 (IGF1), and GHRH receptor, and also stimulated insulin secretion in response to glucose challenge. Exposure of INS-1 cells to GHRH agonists, MR-356 and MR-409, induced activation of ERK and AKT pathways. Agonist MR-409 also significantly increased the levels of cellular cAMP and the phosphorylation of cAMP response element binding protein (CREB) in INS-1 cells. Treatment of rat islets with agonist, MR-409 significantly increased cell proliferation, islet size, and the expression of insulin. In vivo daily s.c. administration of 10 μg MR-409 for 3 wk dramatically reduced the severity of streptozotocin (STZ)-induced diabetes in nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice. The maximal therapeutic benefits with respect to the efficiency of engraftment, ability to reach normoglycemia, gain in body weight, response to high glucose challenge, and induction of higher levels of serum insulin and IGF1 were observed when diabetic mice were transplanted with rat islets preconditioned with GHRH agonist, MR-409, and received additional treatment with MR-409 posttransplantation. This study provides an improved approach to the therapeutic use of GHRH agonists in the treatment of diabetes mellitus. PMID:26474831

  9. Role of hormonal axis, growth hormone - IGF-1, in the therapeutic effect of ghrelin in the course of cerulein-induced acute pancreatitis.

    PubMed

    Ceranowicz, D; Warzecha, Z; Dembinski, A; Ceranowicz, P; Cieszkowski, J; Kusnierz-Cabala, B; Tomaszewska, R; Kuwahara, A; Kato, I

    2010-10-01

    Ghrelin is a ligand for growth hormone secretagogue receptor and stimulates release of growth hormone (GH). Recent studies have shown that treatment with ghrelin exhibits protective and therapeutic effect in the course of experimental pancreatitis. The aim of present study was to examine the role of GH and insulin-like growth factor-1 (IGF-1) in these effects. Acute pancreatitis was induced by cerulein. Study was performed on pituitary-intact hypophysectomized rats. Ghrelin was administered twice a day at the dose of 8 nmol/kg/dose. IGF-1 was given twice a day at the dose of 20 nmol/kg/dose. The severity of acute pancreatitis was assessed 0 h or 1, 2, 3, 5 and 10 days after the last dose of cerulein. Administration of cerulein led to the development of acute edematous pancreatitis. In pituitary-intact rats, treatment with ghrelin reduced biochemical indexes of the severity of acute pancreatitis and morphological signs of pancreatic damage, leading to faster regeneration of the pancreas reduction in serum concentration of pro-inflammatory interleukin-1β and decrease in serum activity of amylase and lipase. These effects were accompanied with an improvement of pancreatic blood flow and an increase in pancreatic DNA synthesis. Hypophysectomy delayed the healing of the pancreas and abolished the therapeutic effect of ghrelin. In hypophysectomized rats with pancreatitis, treatment with IGF-1 exhibits therapeutic effect similar to that observed in ghrelin-treated rats with the intact pituitary. We conclude that therapeutic effect of ghrelin in cerulein-induced pancreatitis is indirect and depends on the release of GH and IGF-1.

  10. Restraint-induced changes in serum luteinizing hormone, prolactin, growth hormone and corticosterone levels in rats: effect of superior cervical ganglionectomy.

    PubMed

    Martín, A I; López-Calderón, A; Tresguerres, J A; González-Quijano, M I; Cardinali, D P

    1995-02-01

    From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Development of a porcine follicle-stimulating hormone and porcine luteinizing hormone induced ovulation protocol in the seasonally anoestrus brushtail possum (Trichosurus vulpecula).

    PubMed

    Glazier, A M; Molinia, F C

    2002-01-01

    Monovulatory brushtail possums (Trichosurus vulpecula) were stimulated with exogenous hormones during seasonal anoestrus to overcome ovarian insensitivity and induce ovulation. Seasonal ovarian insensitivity to pregnant mare serum gonadotrophin (PMSG) was overcome by a new porcine follicle-stimulating hormone/porcine luteinizing hormone (pFSH/pLH) protocol. This protocol was refined because the original treatment produced oocytes with abnormal morphology. Possums (n = 12 per group) received eight injections of pFSH of 1.5, 3.0 or 6.0 mg per injection (at 12-h intervals for 4 consecutive days). Ovulation was induced 12 h after the final pFSH injection with a 4-mg injection of pLH. Control animals were treated with the established protocol of a single injection of 15 IU of PMSG, followed 48 h later with an injection of 4 mg of pLH. All females responded to pFSH/pLH treatment, although optimal stimulation occurred in those receiving 8 x 3 mg pFSH, with 13-14 ovulations and recovery of 11-12 oocytes per female (8 x 1.5 mg pFSH: 13 ovulations, 8-9 oocytes; 8 x 6 mg pFSH: 7-8 ovulations, 4-5 oocytes). In contrast, only seven of 12 females responded to PMSG/pLH and, of those responding, only 2-3 ovulations occurred and only 1-2 oocytes per female were recovered. However, around 80% of oocytes recovered after PMSG/pLH treatment had undergone nuclear maturation (metaphase II/1st polar body) compared with around 60% of oocytes from pFSH/pLH-treated animals. In possums killed from 27 to 39 h after pLH treatment, ovulation onset was first observed from 30 h and by 31.5 h, all animals had completed ovulation. Laparoscopic artificial insemination (LAI) was performed on pFSH/pLH-treated animals to determine whether the oocytes produced were capable of fertilization. Uterine LAI performed 27.5-28.5 h after pLH treatment yielded 11/26 fertilized oocytes (up to 4-cell stage), whereas vaginal LAI performed 13-14 h after pLH treatment yielded 21/53 fertilized oocytes. A proportion of

  12. The pregnancy-induced increase in baseline circulating growth hormone in rats is not induced by ghrelin.

    PubMed

    El-Kasti, M M; Christian, H C; Huerta-Ocampo, I; Stolbrink, M; Gill, S; Houston, P A; Davies, J S; Chilcott, J; Hill, N; Matthews, D R; Carter, D A; Wells, T

    2008-03-01

    The elevation in baseline circulating growth hormone (GH) that occurs in pregnant rats is thought to arise from increased pituitary GH secretion, but the underlying mechanism remains unclear. Distribution, Fourier and algorithmic analyses confirmed that the pregnancy-induced increase in circulating GH in 3-week pregnant rats was due to a 13-fold increase in baseline circulating GH (P < 0.01), without any significant alteration in the parameters of episodic secretion. Electron microscopy revealed that pregnancy resulted in a reduction in the proportion of mammosomatotrophs (P < 0.01) and an increase in type II lactotrophs (P < 0.05), without any significant change in the somatotroph population. However, the density of the secretory granules in somatotrophs from 3-week pregnant rats was reduced (P < 0.05), and their distribution markedly polarised; the granules being grouped nearest the vasculature. Pituitary GH content was not increased, but steady-state GH mRNA levels declined progressively during pregnancy (P < 0.05). In situ hybridisation revealed that pregnancy was accompanied by a suppression of GH-releasing hormone mRNA expression in the arcuate nuclei (P < 0.05) and enhanced somatostatin mRNA expression in the periventricular nuclei (P < 0.05), an expression pattern normally associated with increased GH feedback. Although gastric ghrelin mRNA expression was elevated by 50% in 3-week pregnant rats (P < 0.01), circulating ghrelin, GH-secretagogue receptor mRNA expression and the GH response to a bolus i.v. injection of exogenous ghrelin were all largely unaffected during pregnancy. Although trace amounts of 'pituitary' GH could be detected in the placenta with radioimmunoassay, significant GH-immunoreactivity could not be observed by immunohistochemistry, indicating that rat placenta itself does not produce 'pituitary' GH. Although not excluding the possibility that the pregnancy-associated elevation in baseline circulating GH could arise from alternative extra

  13. Role of splanchnic nerve on steroid-hormone-induced alteration of adrenomedullary catecholamines in untreated and reserpinized pigeon.

    PubMed

    Mahata, S K; Ghosh, A

    1991-01-01

    The aim of the present investigation was to ascertain (1) the effect of steroid hormones (corticosterone, dexamethasone, deoxycorticosterone, progesterone, testosterone and oestrogen) on the neural regulation of adrenomedullary catecholamine (CA) content, and (2) the neural modulation of the effect of glucocorticoid hormones (corticosterone and dexamethasone) on reserpine-induced resynthesis of CA. The experiment was conducted on unilaterally splanchnic-denervated pigeons. The findings revealed that 7 consecutive days of steroid treatments (2.5 mg.kg b.w.-1, i.m.) resulted in significant changes of CA content. Interestingly, the changes of epinephrine (E) content differed significantly between the innervated and denervated glands. This clearly indicates that the splanchnic nerve regulates steroid-induced alterations of E content in the pigeon. The results further revealed that the glucocorticoid hormones augmented reserpine-induced resynthesis of CA specifically in the innervated glands. This confirms that the splanchnic nerve is essential for the synergistic action of glucocorticoids and reserpine in accelerating resynthesis of CA.

  14. Lead (Pb) alters the norepinephrine-induced secretion of luteinizing hormone releasing hormone from the median eminence of adult male rats in vitro

    SciTech Connect

    Bratton, G.R.; Hiney, J.K.; Dees, W.L. )

    1994-01-01

    In the present study, the authors evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E[sub 2] (PGE[sub 2]) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O[sub 2]-5% CO[sub 2]. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 [mu]M. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 [mu]M norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE[sub 2] (2.8 [mu]M) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE[sub 2] released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE[sub 2]-induced release of LHRH. Additionally, Pb did not alter basal PGE[sub 2] release; however, it significantly blocked the NE-induced release of PGE[sub 2]. Since NE-induced LHRH release is mediated by PGE[sub 2], these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE[sub 2] synthesis/release within the ME, resulting in diminished LHRH secretion.

  15. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  16. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-Induced Hormone Secretion during Sepsis.

    PubMed

    Kanczkowski, Waldemar; Sue, Mariko; Bornstein, Stefan R

    2016-01-01

    Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress, adrenal gland rapidly responds with increased secretion of glucocorticoids (GCs) and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure, and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients, levels of both corticotropin-releasing hormone and adrenocorticotropin, the two major regulators of adrenal hormone production, are suppressed. Levels of GCs, however, remain normal or are elevated in these patients, suggesting a shift from central to local intra-adrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced GC metabolism and activation of intra-adrenal cellular systems composed of adrenocortical and adrenomedullary cells, endothelial cells, and resident and recruited immune cells play a key role. Hence, dysregulated function of any of these cells and cellular compartments can ultimately affect adrenal stress response. The purpose of this mini review is to highlight recent insights into our understanding of the adrenal gland microenvironment and its role in coordination of stress-induced hormone secretion.

  17. Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-Induced Hormone Secretion during Sepsis

    PubMed Central

    Kanczkowski, Waldemar; Sue, Mariko; Bornstein, Stefan R.

    2016-01-01

    Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress, adrenal gland rapidly responds with increased secretion of glucocorticoids (GCs) and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure, and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients, levels of both corticotropin-releasing hormone and adrenocorticotropin, the two major regulators of adrenal hormone production, are suppressed. Levels of GCs, however, remain normal or are elevated in these patients, suggesting a shift from central to local intra-adrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced GC metabolism and activation of intra-adrenal cellular systems composed of adrenocortical and adrenomedullary cells, endothelial cells, and resident and recruited immune cells play a key role. Hence, dysregulated function of any of these cells and cellular compartments can ultimately affect adrenal stress response. The purpose of this mini review is to highlight recent insights into our understanding of the adrenal gland microenvironment and its role in coordination of stress-induced hormone secretion. PMID:28018291

  18. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  19. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors

    PubMed Central

    West, Daniel W. D.; Burd, Nicholas A.; Tang, Jason E.; Moore, Daniel R.; Staples, Aaron W.; Holwerda, Andrew M.; Baker, Steven K.

    2010-01-01

    The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 ± 1.2 yr, body mass index = 23.1 ± 0.6 kg/m2) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition × training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men. PMID:19910330

  20. Inhibition of L-dopa induced growth hormone release in normal and diabetic subjects by glucose administration.

    PubMed

    Vigas, M; Klimes, I; Jurcovicova, J; Kolesar, P; Repcekova-Jezova, D

    1977-12-01

    Administration of L-dopa 1 g induced an increase of plasma growth hormone (GH) levels in seven of ten healthy volunteers and in six of ten hyperglycemic insulin-dependent diabetic subjects; the maximal GH response was higher in normal subjects. Addition of 100 g glucose orally to the L-dopa completely abolished the GH response of both groups. The difference between the effect of endogenous hyperglycemia and the effect of a sudden increase of blood sugar after glucose administration on L-dopa induced GH release in diabetic subjects may be explain by the resetting of the hypothalamic control for pituitary GH release to higher levels of blood glucose.

  1. UV-radiation-induced electron emission by hormones. Hypothesis for specific communication mechanisms

    NASA Astrophysics Data System (ADS)

    Getoff, Nikola

    2009-11-01

    The highlights of recently observed electron emission from electronically excited sexual hormones (17β-estradiol, progesterone, testosterone) and the phytohormone genistein in polar media are briefly reviewed. The electron yield, Q(e aq-), dependence from substrate concentration, hormone structure, polarity of solvent, absorbed energy and temperature are discussed. The hormones reactivity with e aq- and efficiency in electron transfer ensure them the ability to communicate with other biological systems in an organism. A hypothesis is presented for the explanation of the mechanisms of the distinct recognition of signals transmitted by electrons, originating from different types of hormones to receiving centres. Biological consequences of the electron emission in respect to cancer are mentioned.

  2. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

    PubMed Central

    Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

    2016-01-01

    Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

  3. Hormone induced expression of brush border lactase in suckling rat intestine.

    PubMed

    Chaudhry, Kamaljit Kaur; Mahmood, Safrun; Mahmood, Akhtar

    2008-05-01

    The postnatal development of intestine is associated with a decline in brush border lactase activity in rodents. This is similar to adulthood hypolactasia, a phenomenon prevalent in humans worldwide. In the present study, the effect of luminal proteases from adult rat intestine was studied in vitro on intestinal lactase activity in saline control, thyroxine, insulin and cortisone treated rat pups. Lactase levels were determined by enzyme analysis and Western blotting. mRNA levels encoding lactase were determined by Northern blotting. Administration of thyroxine for 4 days reduced (P<0.05) lactase activity, but insulin treatment had no effect in 8-day-old rat intestine. However, cortisone administration augmented (P<0.01) lactase activity, under these conditions. Western blot analysis showed decreased lactase signal corresponding to 220-kDa protein band in thyroxine treated animals. However, the intensity of lactase signal was high in cortisone treated animals compared to controls. mRNA levels encoding lactase showed a 6.8-kb mRNA transcript in saline and hormone treated rats. mRNA levels encoding lactase were increased in cortisone treated animals but were reduced in thyroxine injected pups compared to controls. Microvillus membranes from saline (P<0.01) and thyroxine (P<0.05) or insulin (P<0.01) treated rats upon incubation with luminal wash from adult rat intestine showed a significant decline in lactase activity. These findings suggest that thyroxine, insulin or cortisone induced changes in lactase expression in suckling rat intestine make it susceptible to luminal proteases, which may in part be responsible for observed maturational decline in lactase activity in adult rat intestine.

  4. Impact of low-level thyroid hormone disruption induced by propylthiouracil on brain development and function.

    PubMed

    Gilbert, Mary E

    2011-12-01

    The critical role of thyroid hormone (TH) in brain development is well-established. Evidence shows that severe deficiencies lead to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degrees of developmental hypothyroidism by administration of low doses of the TH synthesis inhibitor, propylthiouracil (PTU 0, 1, 2, and 3 ppm) to the drinking water of pregnant rats. This regimen produced dose-dependent reductions in circulating levels of T4 in dams and offspring on postnatal days (PN) 15 and 22, with return to control levels in adulthood upon termination of treatment at weaning. Modest reductions in T3 were observed in the high-dose group on PN15. Synaptic function in the dentate gyrus was examined in adult euthyroid offspring using in vivo field potentials. Excitatory synaptic transmission (excitatory postsynaptic potential [EPSP] slope amplitude) was significantly reduced at 2 and 3 ppm PTU, with no statistically reliable effect detected in the population spike. Paired-pulse functions estimating the integrity of inhibitory synaptic processing were modestly reduced by 3 ppm PTU. Long-term potentiation (LTP) of the EPSP slope was impaired at all dose levels. Trace fear conditioning to context and to cue was impaired at the highest dose level when a distractor stimulus was present, whereas conditioning in a standard trace fear paradigm paradoxically revealed "enhanced" performance at the intermediate dose and a return to control values in the high-dose group. Biphasic dose-response profiles were evident in some measures (trace fear conditioning and LTP) but not others and serve to exemplify the complexity of the role of TH in brain development and its consequences for brain function.

  5. Steroid sex hormone dynamics during estradiol-17β induced gonadal differentiation in Paralichthys olivaceus (Teleostei)

    NASA Astrophysics Data System (ADS)

    Sun, Peng; You, Feng; Liu, Mengxia; Wu, Zhihao; Wen, Aiyun; Li, Jun; Xu, Yongli; Zhang, Peijun

    2010-03-01

    Steroid sex hormones, such as estradiol-17β (E2) and testosterone (T), are important regulators of sex change in fish. In this study, we examined the effects of E2 treatment on the dynamics of E2 and T during gonadal differentiation in the olive flounder Paralichthys olivaceus using histology and radioimmunoassay (RIA). Flounder larvae were divided into five groups (G0-G4), and fed with 0 (control), 0.2, 2, 20 and 100 mg E2/kg feed from 35 to 110 day post hatching (dph). Fish growth in the G1 and G2 groups was not significantly different from that of the control group ( P>0.05), while fish in the G3 and G4 groups were less active and showed growth depression and high mortality. The gonads of fish in the G3 and G4 groups were smaller and surrounded by hyperplastic connective tissue. The frequency of females in the G0-G4 groups was 54.5%, 75.0%, 100%, 100% and 93.3%, respectively. The RIA analyses of E2 and T showed that T levels decreased during gonadal differentiation, and increased slightly at the onset of ovarian differentiation, while E2 levels increased gradually and peaked at the onset of ovarian differentiation in the control group. In the E2-treated groups, T levels decreased before the onset of ovarian differentiation. E2 levels were high on the 48 dph, but declined to a lower level on the 54 dph, and then increased gradually during gonadal differentiation. And a sharp increase of E2 levels were observed in all E2-treated groups at the onset of ovarian differentiation. The data suggest that T and E2 play important roles during gonadal differentiation, and an E2 dose of 2 mg/kg feed could induce sex reversal in P. olivaceus.

  6. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells.

    PubMed

    Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette; Blondeau, Bertrand; Riveline, Jean-Pierre

    2016-01-01

    Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells.

  7. Bioelectrical activity of porcine oviduct and uterus during spontaneous and induced estrus associated with cyclic hormone changes.

    PubMed

    Pawliński, Bartosz; Domino, Małgorzata; Aniołek, Olga; Ziecik, Adam; Gajewski, Zdzislaw

    2016-12-01

    It is widely accepted that uterine contraction is initiated by spontaneous generation of electrical activity at a cellular level in the form of action potentials. Such action potential events, when they involve many myometrial cells and occur in immediate succession, are described by their amplitude and duration. In an effort to improve clinical management of uterine contractions, research has focused on determination of the properties of the reproductive tract's electrical activity under hormonal stimulation. The aim of this study was to evaluate the myoelectric activity (amplitude and duration) of the oviduct and the uterus in relation to plasma concentration of LH, estradiol (E2), and progesterone (P4) during spontaneous and induced estrus in gilts. The course of the experiment was divided into eight periods defined by hormone concentrations (LH, P4, and E2) and time intervals before and after the start of the LH surge. Myoelectric signals were recorded, and the hormone levels were measured during proestrus and estrus in natural and hormone-induced estrus cycle. During the natural estrus, the LH surge was longer than after hormonal stimulation (28 vs. 20 hours) and suggested an inverse relationship between the LH concentration and the duration of myoelectric activity (SR = -0.68). Analyses of the records of the amplitudes and durations of the electromyography activity in uterine horns and oviducts showed significant differences between spontaneous and induced estrus (P < 0.05). During induced estrus, the LH surge began earlier (T1 vs. T2) and increased more (7.46 vs. 6.50 ng/mL) than during spontaneous estrus. This observation suggests a direct relationship between the LH concentration and the amplitude of the myoelectric activity (Spearman rank correlation = 0.71). The significantly higher duration and amplitude of the activity in the isthmus of the oviduct and the uterus during induced estrus shortly after the onset of standing heat (4-8 hours after

  8. Ethylene-induced transcriptional and hormonal responses at the onset of sugarcane ripening

    PubMed Central

    Cunha, Camila P.; Roberto, Guilherme G.; Vicentini, Renato; Lembke, Carolina G.; Souza, Glaucia M.; Ribeiro, Rafael V.; Machado, Eduardo C.; Lagôa, Ana M. M. A.; Menossi, Marcelo

    2017-01-01

    The effects of ethephon as a sugarcane ripener are attributed to ethylene. However, the role of this phytohormone at the molecular level is unknown. We performed a transcriptome analysis combined with the evaluation of sucrose metabolism and hormone profiling of sugarcane plants sprayed with ethephon or aminoethoxyvinylglycine (AVG), an ethylene inhibitor, at the onset of ripening. The differential response between ethephon and AVG on sucrose level and sucrose synthase activity in internodes indicates ethylene as a potential regulator of sink strength. The correlation between hormone levels and transcriptional changes suggests ethylene as a trigger of multiple hormone signal cascades, with approximately 18% of differentially expressed genes involved in hormone biosynthesis, metabolism, signalling, and response. A defence response elicited in leaves favoured salicylic acid over the ethylene/jasmonic acid pathway, while the upper internode was prone to respond to ethylene with strong stimuli on ethylene biosynthesis and signalling genes. Besides, ethylene acted synergistically with abscisic acid, another ripening factor, and antagonistically with gibberellin and auxin. We identified potential ethylene target genes and characterized the hormonal status during ripening, providing insights into the action of ethylene at the site of sucrose accumulation. A molecular model of ethylene interplay with other hormones is proposed. PMID:28266527

  9. Ethylene-induced transcriptional and hormonal responses at the onset of sugarcane ripening.

    PubMed

    Cunha, Camila P; Roberto, Guilherme G; Vicentini, Renato; Lembke, Carolina G; Souza, Glaucia M; Ribeiro, Rafael V; Machado, Eduardo C; Lagôa, Ana M M A; Menossi, Marcelo

    2017-03-07

    The effects of ethephon as a sugarcane ripener are attributed to ethylene. However, the role of this phytohormone at the molecular level is unknown. We performed a transcriptome analysis combined with the evaluation of sucrose metabolism and hormone profiling of sugarcane plants sprayed with ethephon or aminoethoxyvinylglycine (AVG), an ethylene inhibitor, at the onset of ripening. The differential response between ethephon and AVG on sucrose level and sucrose synthase activity in internodes indicates ethylene as a potential regulator of sink strength. The correlation between hormone levels and transcriptional changes suggests ethylene as a trigger of multiple hormone signal cascades, with approximately 18% of differentially expressed genes involved in hormone biosynthesis, metabolism, signalling, and response. A defence response elicited in leaves favoured salicylic acid over the ethylene/jasmonic acid pathway, while the upper internode was prone to respond to ethylene with strong stimuli on ethylene biosynthesis and signalling genes. Besides, ethylene acted synergistically with abscisic acid, another ripening factor, and antagonistically with gibberellin and auxin. We identified potential ethylene target genes and characterized the hormonal status during ripening, providing insights into the action of ethylene at the site of sucrose accumulation. A molecular model of ethylene interplay with other hormones is proposed.

  10. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-04-25

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

  11. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  12. Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain

    PubMed Central

    Schang, Anne-Laure; Van Steenwinckel, Juliette; Chevenne, Didier; Alkmark, Marten; Hagberg, Henrik; Gressens, Pierre; Fleiss, Bobbi

    2014-01-01

    Preterm birth is very strongly associated with maternal/foetal inflammation and leads to permanent neurological deficits. These deficits correlate with the severity of white matter injury, including maturational arrest of oligodendrocytes and hypomyelination. Preterm birth and exposure to inflammation causes hypothyroxinemia. As such, supplementation with thyroxine (T4) seems a good candidate therapy for reducing white matter damage in preterm infants as oligodendrocyte maturation and myelination is regulated by thyroid hormones. We report on a model of preterm inflammation-induced white matter damage, in which induction of systemic inflammation by exposure from P1 to P5 to interleukin-1β (IL-1β) causes oligodendrocyte maturational arrest and hypomyelination. This model identified transient hypothyroidism and wide-ranging dysfunction in thyroid hormone signalling pathways. To test whether a clinically relevant dose of T4 could reduce inflammation-induced white matter damage we concurrently treated mice exposed to IL-1β from P1 to P5 with T4 (20 μg/kg/day). At P10, we isolated O4-positive pre-oligodendrocytes and gene expression analysis revealed that T4 treatment did not recover the IL-1β-induced blockade of oligodendrocyte maturation. Moreover, at P10 and P30 immunohistochemistry for markers of oligodendrocyte lineage (NG2, PDGFRα and APC) and myelin (MBP) similarly indicated that T4 treatment did not recover IL-1β-induced deficits in the white matter. In summary, in this model of preterm inflammation-induced white matter injury, a clinical dose of T4 had no therapeutic efficacy. We suggest that additional pre-clinical trials with T4 covering the breadth and scope of causes and outcomes of perinatal brain injury are required before we can correctly evaluate clinical trials data and understand the potential for thyroid hormone as a widely implementable clinical therapy. PMID:24240022

  13. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

    PubMed

    Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

    2006-06-15

    Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

  14. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D3.

    PubMed

    Kerner, S A; Scott, R A; Pike, J W

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1 alpha,25-dihydroxyvitamin D3. As this protein may represent a marker for bone activity in human disease, we examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. We describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, we define a 21-base-pair DNA element with the sequence 5'-GTGACTCACCGGGTGAACGGG-3', which acts in cis to mediate 1 alpha,25-dihydroxyvitamin D3 inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  15. Heat shock of cultured GC cells enhances the level of triiodothyronine induced growth hormone (GH) and GH messenger ribonucleic acid.

    PubMed

    Shapiro, L E; Katz, C P; DeFesi, C R; Surks, M I

    1989-07-01

    We have previously proposed that the effects of heat shock on thyroid hormone-responsive rat pituitary tumor (GC) cells may be a model relevant to the in vivo effects of nonthyroidal disease on thyroid hormone action. To determine the effects of heat shock on thyroid hormone responses, GC cells (normally cultured at 37 C) were studied after incubation at 41 C. After 18 h at 41 C there was enhanced synthesis of proteins (mol wt, 70,000 and 90,000) considered to be universal markers of the cellular response to heat shock. Incubation at 41 C also resulted in a significant decrease in GC cell viability and (after 24 h) arrest of GC cell growth. However, the induction of GH synthesis by T3 was significantly enhanced in GC cells stressed by incubation at 41 C. The addition of 5 nM T3 to thyroid hormone-depeleted GC cells resulted in a significantly greater (P less than 0.001) accumulation of GH (2642 +/- 280 ng/18 h) during 41 C incubation than during 37 C incubation (1223 +/- 175 ng/18 h). The enhanced T3-induced production of GH was coincident with a proportional increase (P less than 0.05) in cellular GH mRNA determined by dot hybridization analysis. Thus, the stress of 41 C incubation elicits a heat shock response in GC cells characterized by decreased viability and growth arrest, but enhanced accumulation of GH mRNA in response to T3. Our recent report on the identical effects due to the stress of implantation of the Walker 256 carcinoma on T3-induced rat pituitary GH mRNA in vivo suggests that heat shock of cultured GC cells is a valid in vitro model of nonthyroidal disease.

  16. Transcriptome analysis of hormone-induced gene expression in Brachypodium distachyon

    PubMed Central

    Kakei, Yusuke; Mochida, Keiichi; Sakurai, Tetsuya; Yoshida, Takuhiro; Shinozaki, Kazuo; Shimada, Yukihisa

    2015-01-01

    Brachypodium distachyon is a new model plant closely related to wheat and other cereals. In this study, we performed a comprehensive analysis of hormone-regulated genes in Brachypodium distachyon using RNA sequencing technology. Brachypodium distachyon seedlings were treated with eight phytohormones (auxin, cytokinine, brassinosteroid, gibberelline, abscisic acid, ethylene, jasmonate and salicylic acid) and two inhibitors, Brz220 (brassinosteroid biosynthesis inhibitor) and prohexadione (gibberelline biosynthesis inhibitor). The expressions of 1807 genes were regulated in a phytohormone-dependent manner. We compared the data with the phytohormone responses that have reported in rice. Transcriptional responses to hormones are conserved between Bracypodium and rice. Transcriptional regulation by brassinosteroid, gibberellin and ethylene was relatively weaker than those by other hormones. This is consistent with the data obtained from comprehensive analysis of hormone responses reported in Arabidopsis. Brachypodium and Arabidopsis also shared some common transcriptional responses to phytohormones. Alternatively, unique transcriptional responses to phytohormones were observed in Brachypodium. For example, the expressions of ACC synthase genes were up-regulated by auxin treatment in rice and Arabidopsis, but no orthologous ACC synthase gene was up-regulated in Brachypodium. Our results provide information useful to understand the diversity and similarity of hormone-regulated transcriptional responses between eudicots and monocots. PMID:26419335

  17. Transcriptome analysis of hormone-induced gene expression in Brachypodium distachyon.

    PubMed

    Kakei, Yusuke; Mochida, Keiichi; Sakurai, Tetsuya; Yoshida, Takuhiro; Shinozaki, Kazuo; Shimada, Yukihisa

    2015-09-30

    Brachypodium distachyon is a new model plant closely related to wheat and other cereals. In this study, we performed a comprehensive analysis of hormone-regulated genes in Brachypodium distachyon using RNA sequencing technology. Brachypodium distachyon seedlings were treated with eight phytohormones (auxin, cytokinine, brassinosteroid, gibberelline, abscisic acid, ethylene, jasmonate and salicylic acid) and two inhibitors, Brz220 (brassinosteroid biosynthesis inhibitor) and prohexadione (gibberelline biosynthesis inhibitor). The expressions of 1807 genes were regulated in a phytohormone-dependent manner. We compared the data with the phytohormone responses that have reported in rice. Transcriptional responses to hormones are conserved between Bracypodium and rice. Transcriptional regulation by brassinosteroid, gibberellin and ethylene was relatively weaker than those by other hormones. This is consistent with the data obtained from comprehensive analysis of hormone responses reported in Arabidopsis. Brachypodium and Arabidopsis also shared some common transcriptional responses to phytohormones. Alternatively, unique transcriptional responses to phytohormones were observed in Brachypodium. For example, the expressions of ACC synthase genes were up-regulated by auxin treatment in rice and Arabidopsis, but no orthologous ACC synthase gene was up-regulated in Brachypodium. Our results provide information useful to understand the diversity and similarity of hormone-regulated transcriptional responses between eudicots and monocots.

  18. Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats.

    PubMed

    Li, Yan; Raaby, Kasper F; Sánchez, Connie; Gulinello, Maria

    2013-11-01

    Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD) are characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. Studies demonstrated rodent models of progesterone withdrawal (PWD) have a high level of constructive and descriptive validity to model hormonally-induced mood disorders in women. Here we evaluate the effects of several classes of antidepressants in PWD female Long-Evans rats using the forced swim test (FST) as a measure of antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A) receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days of administration, amitriptyline and vortioxetine significantly reduced immobility in the FST whereas fluoxetine and duloxetine were ineffective. After 3 injections over 48 h, neither fluoxetine nor duloxetine reduced immobility, whereas amitriptyline and vortioxetine significantly reduced FST immobility during PWD. When administered acutely during PWD, the 5-HT(1A) receptor agonist, flesinoxan, significantly reduced immobility, whereas the 5-HT(1A) receptor antagonist, WAY-100635, increased immobility. The 5-HT(3) receptor antagonist, ondansetron, significantly reduced immobility, whereas the 5-HT(3) receptor agonist, SR-57227, increased immobility. The 5-HT(7) receptor antagonist, SB-269970, was inactive, although the 5-HT(7) receptor agonist, AS-19, significantly increased PWD-induced immobility. None of the compounds investigated (ondansetron, flesinoxan and SB-269970) improved the effect of fluoxetine during PWD. These data indicate that modulation of specific 5-HT receptor subtypes is critical for manipulating FST immobility in this model of hormone-induced depression.

  19. Protein- and tryptophan-restricted diets induce changes in rat gonadal hormone levels.

    PubMed

    Del Angel-Meza, A R.; Feria-Velasco, A; Ontiveros-Martínez, L; Gallardo, L; Gonzalez-Burgos, I; Beas-Zárate, C

    2001-04-01

    The release of gonadotrophic hormones starts at puberty and, along with the subsequent estral cyclicity, is subject to hormonal feedback systems and to the action of diverse neuroactive substances such as gamma amino butyric acid and catecholamines. This study shows the effect of the administration during 40 days of protein-restricted and corn-based (tryptophan- and lysine-deficient) diets on the serotonin concentration in medial hypothalamic fragments as well as in follicle-stimulating luteinizing hormones, 17-beta-estradiol and progesterone serum levels, and estral cyclicity in 60- and 100-day-old rats (young, mature, and in gestation). In young rats, a delay in vaginal aperture development, and a lengthening of the estral cycle to a continuous anestral state was observed, mainly in the group fed corn. This group showed a 25% decrease in the serotonin concentration compared with the protein-restricted group, which exhibited an increase of 9% over the control group. Luteinizing hormone levels decreased in 16% and 13%, whereas follicle-stimulating hormone increased in 13% and 5% in the young animals of restricted groups, respectively, compared with the control group. Serum progesterone levels decreased only in young restricted versus control animals, and no differences were seen among adult and gestational rats. Serum levels of 17-beta-estradiol in restricted animals showed different concentration patterns, mainly in the corn group, which was higher at the 20th gestational day, falling drastically postpartum. The results obtained in this study show serotonin to be a very important factor in the release of gonadotrophic hormones and the start of puberty.

  20. Reductions in circulating anabolic hormones induced by sustained sleep deprivation in rats.

    PubMed

    Everson, Carol A; Crowley, William R

    2004-06-01

    The main systemic disorders resulting from prolonged sleep deprivation in laboratory animals are a negative energy balance, low circulating thyroid hormones, and host defense impairments. Low thyroid hormones previously have been found caused by altered regulation at the level of the hypothalamus with possible pituitary involvement. The present studies investigated the effects of sleep deprivation on other major anabolic hormonal systems. Plasma growth hormone (GH) concentrations and major secretory bursts were characterized. Insulin-like growth factor I (IGF-I) was evaluated as an integrative marker of peripheral GH effector activity. Prolactin (PRL) was assessed by basal concentrations and by stimulating the pituitary with exogenous thyrotropin-releasing hormone. Leptin was studied for its linkage to metabolic signs of sleep loss and its correspondence to altered neuroendocrine regulation in other disease states. Last, plasma corticosterone was measured to investigate the degree of hypothalamic-pituitary-adrenal activation. Sleep deprivation was produced by the disk-over-water method, a well-established means of selective deprivation of sleep and noninterference with normal waking behaviors. Hormone concentrations were determined in sham comparisons and at intervals during baseline and experimental periods lasting at least 15 days in partially and totally sleep-deprived rats. The results indicate that high-amplitude pulses of GH were nearly abolished and that concentrations of GH, IGF-I, PRL, and leptin all were suppressed by sleep deprivation. Corticosterone concentration was relatively unaffected. Features of these results, such as low GH and low IGF-I, indicate failed negative feedback and point to hypothalamic mechanisms as containing the foci responsible for peripheral signs.

  1. Cobalt-induced hormonal and intracellular alterations in rat ovarian fragments in vitro.

    PubMed

    Roychoudhury, Shubhadeep; Sirotkin, Alexander V; Toman, Robert; Kolesarova, Adriana

    2014-01-01

    The objective of this in vitro study was to examine dose-dependent changes in the secretion activity (progesterone, 17β-estradiol and insulin-like growth factor-I) of rat ovarian fragments after experimental cobalt (Co) administration including the apoptotic potential of Co on rat ovarian fragments by evaluating the expression of apoptotic markers Bax and caspase-3. Ovarian fragments were incubated with cobalt sulphate (CoSO4.7H2O) at the doses 90, 170, 330 and 500 μg.mL(-1) for 24 h and compared with control group without Co addition. Release of progesterone (P4) 17β-estradiol and insulin-like growth factor-I (IGF-I) by ovarian fragments was assessed by RIA, expression of Bax and caspase-3 by SDS-PAGE and Western blotting. Observations show that P4 release by ovarian fragments was significantly (P < 0.05) inhibited after cobalt sulphate addition at higher doses 170-500 μg.mL(-1) used in the study in comparison to control. However, cobalt sulphate addition did not cause any significant change in the release of 17β-estradiol by ovarian fragments at all the doses used in the study (90-500 μg.mL(-1)) in comparison to control. On the contrary, IGF-I release by ovarian fragments was significantly (P < 0.05) stimulated after cobalt sulphate addition at the lowest dose 90 μg.mL(-1) in comparison to control, while other doses did not cause any significant change. Also, addition of cobalt sulphate decreased the expression of both the apoptotic peptides Bax and caspase-3 at the higher doses 170, 330 and 500 μg.mL(-1), but not at the lowest dose 90 μg.mL(-1) used in the study. Obtained results suggest Co induced (1) inhibition in secretion of steroid hormone progesterone, (2) dose-dependent increase in the release of growth factor IGF-I, and (3) decrease in the expression of markers of apoptosis (Bax and caspase-3) of rat ovarian fragments.

  2. Hormonal modulation of food intake in response to low leptin levels induced by hypergravity

    NASA Technical Reports Server (NTRS)

    Moran, M. M.; Stein, T. P.; Wade, C. E.

    2001-01-01

    A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  3. The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

  4. Potential role of cysteine and methionine in the protection against hormonal imbalance and mutagenicity induced by furazolidone in female rats.

    PubMed

    Ahmed, Hanaa H; El-Aziem, Sekena H Abd; Abdel-Wahhab, Mosaad A

    2008-01-14

    The use of nitrofurans as veterinary drugs has been banned in the EU since 1993 due to doubts on the safety of the protein-bound residues of these drugs in edible products. Furazolidone (FUZ) is a nitrofuran drug, which has been used for many years as an antibacterial drug in veterinary practice. The aim of the current study is to investigate the role of L-cysteine and L-methionine in the protection against hormonal imbalance and the genotoxicity induced by FUZ using the micronucleus (MN) assay and random amplified polymorphism DNA (RAPD-PCR) analysis in female rats. Forty female Sprague-Dawley rats were divided into four groups included the untreated control group; a group treated with FUZ (300 mg/kg b.w.); a group treated with a mixture of L-cysteine (300 mg/kg b.w.) and L-methionine (42.8 mg/kg b.w.) and a group treated with FUZ plus the mixture of L-cysteine and L-methionine for 10 days. The results indicated that FUZ induced hormonal disturbances involving thyroid, ovarian and adrenal hormones. Moreover, FUZ increased the micronucleus formation and induced changes in polymorphic band patterns. The combined treatment with FUZ and the mixture of L-cysteine and L-methionine succeeded to prevent or diminish the endocrine disturbance and the clastogenic effects of FUZ. The current study is casting new light on the complex mechanisms underlying the ameliorating action of dietary L-cysteine and L-methionine against FUZ toxicity in experimental animals.

  5. Effect of epidermal growth factor on follicle-stimulating hormone-induced proliferation of granulosa cells from chicken prehierarchical follicles.

    PubMed

    Lin, Jin-xing; Jia, Yu-dong; Zhang, Cai-qiao

    2011-11-01

    The development of ovarian follicular cells is controlled by multiple circulating and local hormones and factors, including follicle-stimulating hormone (FSH) and epidermal growth factor (EGF). In this study, the stage-specific effect of EGF on FSH-induced proliferation of granulosa cells was evaluated in the ovarian follicles of egg-laying chickens. Results showed that EGF and its receptor (EGFR) mRNAs displayed a high expression in granulosa cells from the prehierarchical follicles, including the large white follicle (LWF) and small yellow follicle (SYF), and thereafter the expression decreased markedly to the stage of the largest preovulatory follicle. SYF represents a turning point of EGF/EGFR mRNA expression during follicle selection. Subsequently the granulosa cells from SYF were cultured to reveal the mediation of EGF in FSH action. Cell proliferation was remarkably increased by treatment with either EGF or FSH (0.1-100 ng/ml). This result was confirmed by elevated proliferating cell nuclear antigen (PCNA) expression and decreased cell apoptosis. Furthermore, EGF-induced cell proliferation was accompanied by increased mRNA expressions of EGFR, FSH receptor, and the cell cycle-regulating genes (cyclins D1 and E1, cyclin-dependent kinases 2 and 6) as well as decreased expression of luteinizing hormone receptor mRNA. However, the EGF or FSH-elicited effect was reversed by simultaneous treatment with an EGFR inhibitor AG1478. In conclusion, EGF and EGFR expressions manifested stage-specific changes during follicular development and EGF mediated FSH-induced cell proliferation and retarded cell differentiation in the prehierarchical follicles. These expressions thus stimulated follicular growth before selection in the egg-laying chicken.

  6. Transcription Analysis of Arabidopsis Membrane Transporters and Hormone Pathways during Developmental and Induced Leaf Senescence1[W

    PubMed Central

    van der Graaff, Eric; Schwacke, Rainer; Schneider, Anja; Desimone, Marcelo; Flügge, Ulf-Ingo; Kunze, Reinhard

    2006-01-01

    A comparative transcriptome analysis for successive stages of Arabidopsis (Arabidopsis thaliana) developmental leaf senescence (NS), darkening-induced senescence of individual leaves attached to the plant (DIS), and senescence in dark-incubated detached leaves (DET) revealed many novel senescence-associated genes with distinct expression profiles. The three senescence processes share a high number of regulated genes, although the overall number of regulated genes during DIS and DET is about 2 times lower than during NS. Consequently, the number of NS-specific genes is much higher than the number of DIS- or DET-specific genes. The expression profiles of transporters (TPs), receptor-like kinases, autophagy genes, and hormone pathways were analyzed in detail. The Arabidopsis TPs and other integral membrane proteins were systematically reclassified based on the Transporter Classification system. Coordinate activation or inactivation of several genes is observed in some TP families in all three or only in individual senescence types, indicating differences in the genetic programs for remobilization of catabolites. Characteristic senescence type-specific differences were also apparent in the expression profiles of (putative) signaling kinases. For eight hormones, the expression of biosynthesis, metabolism, signaling, and (partially) response genes was investigated. In most pathways, novel senescence-associated genes were identified. The expression profiles of hormone homeostasis and signaling genes reveal additional players in the senescence regulatory network. PMID:16603661

  7. Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

    NASA Technical Reports Server (NTRS)

    Meehan, R. T.

    1986-01-01

    Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

  8. Changes in hormone and stress-inducing activities of municipal wastewater in a conventional activated sludge wastewater treatment plant.

    PubMed

    Wojnarowicz, Pola; Yang, Wenbo; Zhou, Hongde; Parker, Wayne J; Helbing, Caren C

    2014-12-01

    Conventional municipal wastewater treatment plants do not efficiently remove contaminants of emerging concern, and so are primary sources for contaminant release into the aquatic environment. Although these contaminants are present in effluents at ng-μg/L concentrations (i.e. microcontaminants), many compounds can act as endocrine disrupting compounds or stress-inducing agents at these levels. Chemical fate analyses indicate that additional levels of wastewater treatment reduce but do not always completely remove all microcontaminants. The removal of microcontaminants from wastewater does not necessarily correspond to a reduction in biological activity, as contaminant metabolites or byproducts may still be biologically active. To evaluate the efficacy of conventional municipal wastewater treatment plants to remove biological activity, we examined the performance of a full scale conventional activated sludge municipal wastewater treatment plant located in Guelph, Ontario, Canada. We assessed reductions in levels of conventional wastewater parameters and thyroid hormone disrupting and stress-inducing activities in wastewater at three phases along the treatment train using a C-fin assay. Wastewater treatment was effective at reducing total suspended solids, chemical and biochemical oxygen demand, and stress-inducing bioactivity. However, only minimal reduction was observed in thyroid hormone disrupting activities. The present study underscores the importance of examining multiple chemical and biological endpoints in evaluating and monitoring the effectiveness of wastewater treatment for removal of microcontaminants.

  9. Juvenile hormone prevents 20-hydroxyecdysone-induced metamorphosis by regulating the phosphorylation of a newly identified broad protein.

    PubMed

    Cai, Mei-Juan; Liu, Wen; Pei, Xu-Yang; Li, Xiang-Ru; He, Hong-Juan; Wang, Jin-Xing; Zhao, Xiao-Fan

    2014-09-19

    The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and metamorphosis. By contrast, juvenile hormone (JH) prevents metamorphosis. However, the mechanism by which JH inhibits metamorphosis remains unclear. In this study, we propose that JH induces the phosphorylation of Broad isoform Z7 (BrZ7), a newly identified protein, to inhibit 20E-mediated metamorphosis in the lepidopteran insect Helicoverpa armigera. The knockdown of BrZ7 in larvae inhibited metamorphosis by repressing the expression of the 20E response gene. BrZ7 was weakly expressed and phosphorylated during larval growth but highly expressed and non-phosphorylated during metamorphosis. JH regulated the rapid phosphorylation of BrZ7 via a G-protein-coupled receptor-, phospholipase C-, and protein kinase C-triggered pathway. The phosphorylated BrZ7 bound to the 5'-regulatory region of calponin to regulate its expression in the JH pathway. Exogenous JH induced BrZ7 phosphorylation to prevent metamorphosis by suppressing 20E-related gene transcription. JH promoted non-phosphorylated calponin interacting with ultraspiracle protein to activate the JH pathway and antagonize the 20E pathway. This study reveals one of the possible mechanisms by which JH counteracts 20E-regulated metamorphosis by inducing the phosphorylation of BrZ7.

  10. Hormonal Correlates of Clozapine-Induced Weight Gain in Psychotic Children: An Exploratory Study

    ERIC Educational Resources Information Center

    Sporn, Alexandra L.; Bobb, Aaron J.; Gogtay, Nitin; Stevens, Hanna; Greenstein, Deanna K.; Clasen, Liv S.; Tossell, Julia W.; Nugent, Thomas; Gochman, Peter A.; Sharp, Wendy S.; Mattai, Anand; Lenane, Marge C.; Yanovski, Jack A.; Rapoport, Judith L.

    2005-01-01

    Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls…

  11. Hormone-induced repression of a peroxidase isozyme in plant tissue.

    PubMed

    Ockerse, R; Siegel, B Z; Galston, A W

    1966-01-28

    Young stem sections of dwarf peas (Progress No. 9) grown in light contain at least seven peroxidase isozymes separable by electrophoresis on starch gel. An eighth isozyme appears as the tissue elongates and ages, on or off the plant. The appearance of this isozyme in excised sections is repressed by application of the plant growth hormone, indole-3-acetic acid.

  12. Effects of Gadolinium-Based Contrast Agents on Thyroid Hormone Receptor Action and Thyroid Hormone-Induced Cerebellar Purkinje Cell Morphogenesis

    PubMed Central

    Ariyani, Winda; Iwasaki, Toshiharu; Miyazaki, Wataru; Khongorzul, Erdene; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito; Koibuchi, Noriyuki

    2016-01-01

    Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical for the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and TH-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8 to 10−6M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 to 10−4M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10−9M T4 was augmented by low-dose Gd-DTPA-BMA (10−7M) but was suppressed by higher dose (10−5M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10−9M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10−5M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker

  13. Cyclic AMP Modulation of Estrogen-Induced Effects: A Novel Mechanism for Hormonal Resistance in Breast Cancer

    DTIC Science & Technology

    1997-10-01

    Marden E, Martin G, MacKay H, Abbon- danza C, Brown M 1994 Estrogen receptor-associated proteins: possible mediators of hormone-induced tran...cells. Nucleic Ac- ids Res 19:6595-6602 42. Halachmi S, Marden E, Martin G, MacKay H, Abbon- danza C, Brown M 1994 Estrogen receptor-associated...the estrogen re- ceptor. EMBO J 14:3741-3751 26. Halachmi S, Marden E, Martin G, MacKay H, Abbon- danza C, Brown M 1994 Estrogen receptor-associated

  14. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    SciTech Connect

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  15. Specificity of herbivore-induced hormonal signaling and defensive traits in five closely related milkweeds (Asclepias spp.).

    PubMed

    Agrawal, Anurag A; Hastings, Amy P; Patrick, Eamonn T; Knight, Anna C

    2014-07-01

    Despite the recognition that phytohormonal signaling mediates induced responses to herbivory, we still have little understanding of how such signaling varies among closely related species and may generate herbivore-specific induced responses. We studied closely related milkweeds (Asclepias) to link: 1) plant damage by two specialist chewing herbivores (milkweed leaf beetles Labidomera clivicolis and monarch caterpillars Danaus plexippus); 2) production of the phytohormones jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA); 3) induction of defensive cardenolides and latex; and 4) impacts on Danaus caterpillars. We first show that A. syriaca exhibits induced resistance following monarch herbivory (i.e., reduced monarch growth on previously damaged plants), while the defensively dissimilar A. tuberosa does not. We next worked with a broader group of five Asclepias, including these two species, that are highly divergent in defensive traits yet from the same clade. Three of the five species showed herbivore-induced changes in cardenolides, while induced latex was found in four species. Among the phytohormones, JA and ABA showed specific responses (although they generally increased) to insect species and among the plant species. In contrast, SA responses were consistent among plant and herbivore species, showing a decline following herbivore attack. Jasmonic acid showed a positive quantitative relationship only with latex, and this was strongest in plants damaged by D. plexippus. Although phytohormones showed qualitative tradeoffs (i.e., treatments that enhanced JA reduced SA), the few significant individual plant-level correlations among hormones were positive, and these were strongest between JA and ABA in monarch damaged plants. We conclude that: 1) latex exudation is positively associated with endogenous JA levels, even among low-latex species; 2) correlations among milkweed hormones are generally positive, although herbivore damage induces a

  16. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    SciTech Connect

    Hannon, Patrick R. Brannick, Katherine E. Wang, Wei Gupta, Rupesh K. Flaws, Jodi A.

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  17. Optimization of the T3-induced Xenopus metamorphosis assay for detecting thyroid hormone signaling disruption of chemicals.

    PubMed

    Yao, Xiaofang; Chen, Xiaoying; Zhang, Yinfeng; Li, Yuanyuan; Wang, Yao; Zheng, Zongming; Qin, Zhanfen; Zhang, Qingdong

    2017-02-01

    T3-induced Xenopus metamorphosis is an ideal model for detecting thyroid hormone (TH) signaling disruption of chemicals. To optimize the T3-induced Xenopus assay and improve its sensitivity and reproducibility, we intend to develop quantitatively morphological endpoints and choose appropriate concentrations and exposure durations for T3 induction. Xenopus laevis at stage 52 were exposed to series of concentrations of T3 (0.31-2.5nmol/L) for 6days. By comparing morphological changes induced by T3, we propose head area, mouth width, unilateral brain width/brain length, and hindlimb length/snout-vent length as quantitative parameters for characterizing T3-induced morphological changes, with body weight as a parameter for indicating integrated changes. By analyzing time-response curves, we found that following 4-day exposure, T3-induced grossly morphological changes displayed linear concentration-response curves, with moderate morphological changes resulting from 1.25nmol/L T3 exposure. When using grossly morphological endpoints to detect TH signaling disruption, we propose 4days as exposure duration of T3, with concentrations close to 1.25nmol/L as induction concentrations. However, it is appropriate to examine morphological and molecular changes of the intestine on day 2 due to their early response to T3. The quantitative endpoints and T3 induction concentrations and durations we determined would improve the sensitivity and the reproducibility of the T3-induced Xenopus metamorphosis assay.

  18. UV filters induce transcriptional changes of different hormonal receptors in Chironomus riparius embryos and larvae.

    PubMed

    Ozáez, Irene; Aquilino, Mónica; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2016-07-01

    Organic ultraviolet (UV) filters are emerging contaminants that are ubiquitous in fresh and marine aquatic systems due to their extensive use in cosmetics, plastics, paints, textiles, and many other industrial products. The estrogenic effects of organic UV filters have been long demonstrated in vertebrates, and other hormonal activities may be altered, according to more recent reports. The impact of UV filters on the endocrine system of invertebrates is largely unknown. We have previously reported that some UV filters may affect ecdysone-related genes in the aquatic insect Chironomus riparius, an ecotoxicologically important model organism. To further analyze other possible effects on endocrine pathways, we first characterized four pivotal genes related with hormonal pathways in insects; thereafter, these genes were assessed for alterations in transcriptional activity after exposure to 4-methylbenzylidene camphor (4MBC) or benzophenone-3 (BP-3), two extensively used sunscreens. We found that both chemicals disturbed the expression of all four genes analyzed: hormonal receptor 38 (HR38), methoprene-tolerant (Met), membrane-associate progesterone receptor (MAPR) and insulin-like receptor (INSR), measured by changes in mRNA levels by real-time PCR. An upregulatory effect at the genomic level was detected in different developmental stages. Interestingly, embryos appeared to be more sensitive to the action of the UV filters than larvae. Our results suggest that the risk of disruption through different endocrine routes is not negligible, considering the significant effects of UV filters on key hormonal receptor and regulatory genes. Further effort is needed to develop environmental risk assessment studies on these pollutants, particularly for aquatic invertebrate model organisms.

  19. Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes and uterus but not in the ovary of rats.

    PubMed

    Farombi, E O; Abolaji, A O; Adedara, I A; Maduako, I; Omodanisi, I

    2015-01-01

    Artemisinin is an antimalarial drug previously reported to induce neurotoxicity and embryotoxicity in animal models. This study investigated the erythrocytes and reproductive toxicity potentials of artemisinin in female rats. Animals were randomly divided into four study groups of eight rats each. The control group (group I) received corn oil, the vehicle, while groups II-IV were orally exposed to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric intubation for 7 consecutive days. Subsequently, we evaluated the impact of artemisinin on the endocrine environment and selected markers of oxidative damage and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and decreased catalase, glutathione peroxidase and superoxide dismutase activities in erythrocytes and uterus of rats compared with control group (p < 0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels and catalase activity, while ovarian and uterine histological assessment revealed absence of visible lesions. Moreover, artemisinin significantly decreased follicle-stimulating hormone and increased progesterone levels compared with control (p < 0.05). Thus, these data suggest that in the absence of malarial parasite infection, artemisinin induced hormonal imbalance and oxidative damage in the erythrocytes and uterus but spared the ovary of rats.

  20. Oral administration of omega-7 palmitoleic acid induces satiety and the release of appetite-related hormones in male rats.

    PubMed

    Yang, Zhi-Hong; Takeo, Jiro; Katayama, Masashi

    2013-06-01

    We have analyzed the effect of palmitoleic acid on short-term food intake in male rats. Administration of omega-7 palmitoleic acid by oral gavage significantly decreased food intake compared to palmitic acid, omega-9 oleic acid, or a vehicle control. Palmitoleic acid exhibited a dose-dependent effect in this context and did not cause general malaise. A triglyceride form of palmitoleate also decreased food intake, whereas olive oil, which is rich in oleic acid, did not. Palmitoleic acid accumulated within the small intestine in a dose-dependent fashion and elevated levels of the satiety hormone cholecystokinin (CCK). Both protein and mRNA levels of CCK were affected in this context. The suppression of food intake by palmitoleic acid was attenuated by intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. Palmitoleic acid did not alter the expression of peroxisome proliferator-activated receptor alpha (PPARα) target genes, and a PPARα antagonist did not affect palmitoleic acid-induced satiety. This suggests that the PPARα pathway might not be involved in suppressing food intake in response to palmitoleic acid. We have shown that orally administered palmitoleic acid induced satiety, enhanced the release of satiety hormones in rats.

  1. Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes

    PubMed Central

    Ye, Hanfeng; Ha, Mei; Yang, Min; Yue, Ping; Xie, Zhengyuan; Liu, Changjiang

    2017-01-01

    Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP. PMID:28065941

  2. Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes.

    PubMed

    Ye, Hanfeng; Ha, Mei; Yang, Min; Yue, Ping; Xie, Zhengyuan; Liu, Changjiang

    2017-01-09

    Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP.

  3. Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells.

    PubMed

    Basak, Onur; Beumer, Joep; Wiebrands, Kay; Seno, Hiroshi; van Oudenaarden, Alexander; Clevers, Hans

    2017-02-02

    Lgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into three-dimensional organoids containing all intestinal epithelial cell types at near-normal ratios. Conditions to generate the main cell types (enterocyte, goblet cells, Paneth cells, and M cells) are well established, but signals to induce the spectrum of hormone-producing enteroendocrine cells (EECs) have remained elusive. Here, we induce Lgr5+ stem cell quiescence in vitro by blocking epidermal growth factor receptor (EGFR) or mitogen-associated protein kinase (MAPK) signaling pathways in organoids and show that their quiescent state is readily reverted. Quiescent Lgr5+ stem cells acquire a distinct molecular signature biased toward EEC differentiation. Indeed, combined inhibition of Wnt, Notch, and MAPK pathways efficiently generates a diversity of EEC hormone-expressing subtypes in vitro. Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and provide an approach for the study of the elusive EECs in a defined environment.

  4. Dimeric Arrangement of the Parathyroid Hormone Receptor and a Structural Mechanism for Ligand-induced Dissociation

    SciTech Connect

    Pioszak, Augen A.; Harikumar, Kaleeckal G.; Parker, Naomi R.; Miller, Laurence J.; Xu, H. Eric

    2010-06-25

    The parathyroid hormone receptor (PTH1R) is a class B G protein-coupled receptor that is activated by parathyroid hormone (PTH) and PTH-related protein (PTHrP). Little is known about the oligomeric state of the receptor and its regulation by hormone. The crystal structure of the ligand-free PTH1R extracellular domain (ECD) reveals an unexpected dimer in which the C-terminal segment of both ECD protomers forms an {alpha}-helix that mimics PTH/PTHrP by occupying the peptide binding groove of the opposing protomer. ECD-mediated oligomerization of intact PTH1R was confirmed in living cells by bioluminescence and fluorescence resonance energy transfer experiments. As predicted by the structure, PTH binding disrupted receptor oligomerization. A receptor rendered monomeric by mutations in the ECD retained wild-type PTH binding and cAMP signaling ability. Our results are consistent with the hypothesis that PTH1R forms constitutive dimers that are dissociated by ligand binding and that monomeric PTH1R is capable of activating G protein.

  5. Prophylactic effect of Nigella sativa against lead acetate induced changes in spermiogram, reproductive hormones and gonadal histology of rats

    PubMed Central

    Assi, Mohammed Abdulrazzaq; Hezmee, Mohammed Noor Mohd; Abba, Yusuf; Yusof, Md Sabri Md; Haron, Abd Wahid; Rajion, Mohamed Ali; Al-Zuhairy, Mashaan Abbas

    2016-01-01

    Aim: This study was designed to evaluate the prophylactic effect of Nigella sativa (NS) treatment on toxic effects induced by lead acetate (LA) on the reproductive hormones, spermiogram and gonadal histology of rats. Materials and Methods: A total of 20 Sprague-Dawley rats were divided into four groups of five rats each. Group 1 (negative control [NC]) was the NC and was given distilled water, Group 2 served as the positive control (PC) and was administered 10 mg/kg/day of LA per overall survival (OS), Group 3 (T1) was administered 200 mg/kg/daily of NS per OS for a month, and Group 4 (T2) was pretreated with 200 mg/kg/daily of NS per OS for 1 month, followed by 10 mg/kg/daily of LA alone per OS for another. The rats were euthanized at the end of the experimental period for collection of blood and the right caudal epididymis and testis. Serum was used for determination of reproductive hormones by using radioimmunoassay kits. The epididymal segment was cut and homogenized in phosphate-buffered saline, and the homogenate was used for determination of the spermiogram parameters such as sperm concentration, sperm viability, percentage of live sperm, motility and abnormality. Both the epididymis and testis were fixed in 10% buffered formalin for histological processing. Results: The sperm concentration, general, and individual motilities were higher (p<0.05) in the NC and T1 animals, while the T2 had intermediate and the PC had lower (p<0.05) values of each parameter. The percentage sperm viability was higher (p<0.05) in the T1 and lower (p<0.05) in the PC group. However, percentage abnormality was lower in T1, comparable in NC and T2, and higher (p<0.05) in PC. Spermatogenic cell population and epididymal sperm reserve (ESR) were optimal in control and pretreated animals, while the PC had lower spermatids and ESR. The concentration of estradiol (EST) was lower (p<0.05) in the PC and T2, while leuteinizing hormone (LH) concentration was lower (p<0.05) in the PC, and

  6. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    PubMed

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  7. Physical Exercise Counteracts Stress-induced Upregulation of Melanin-concentrating Hormone in the Brain and Stress-induced Persisting Anxiety-like Behaviors

    PubMed Central

    Kim, Tae-Kyung

    2016-01-01

    Chronic stress induces anxiety disorders, whereas physical exercise is believed to help people with clinical anxiety. In the present study, we investigated the mechanisms underlying stress-induced anxiety and its counteraction by exercise using an established animal model of anxiety. Mice treated with restraint for 2 h daily for 14 days exhibited anxiety-like behaviors, including social and nonsocial behavioral symptoms, and these behavioral impairments lasted for more than 12 weeks after the stress treatment was removed. Despite these lasting behavioral changes, wheel-running exercise treatment for 1 h daily from post-stress days 1 - 21 counteracted anxiety-like behaviors, and these anxiolytic effects of exercise persisted for more than 2 months, suggesting that anxiolytic effects of exercise stably induced. Repeated restraint treatment up-regulated the expression of the neuropeptide, melanin-concentrating hormone (MCH), in the lateral hypothalamus, hippocampus, and basolateral amygdala, the brain regions important for emotional behaviors. In an in vitro study, treatment of HT22 hippocampal cells with glucocorticoid increased MCH expression, suggesting that MCH upregulation can be initially triggered by the stress hormone, corticosterone. In contrast, post-stress treatment with wheel-running exercise reduced the stress-induced increase in MCH expression to control levels in the lateral hypothalamus, hippocampus and basolateral amygdala. Administration of an MCH receptor antagonist (SNAP94847) to stress-treated mice was therapeutic against stress-induced anxiety-like behaviors. These results suggest that repeated stress produces long-lasting anxiety-like behaviors and upregulates MCH in the brain, while exercise counteracts stress-induced MCH expression and persisting anxiety-like behaviors. PMID:27574483

  8. Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.

    PubMed Central

    Lehmann, J M; Zhang, X K; Graupner, G; Lee, M O; Hermann, T; Hoffmann, B; Pfahl, M

    1993-01-01

    Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands. Images PMID:8246986

  9. Investigations of receptor-mediated phagocytosis by hormone-induced (imprinted) Tetrahymena pyriformis.

    PubMed

    Kovács, P; Sundermann, C A; Csaba, G

    1996-08-15

    Receptor-mediated endocytosis by Tetrahvmena pyriformis was studied using tetramethylrhodamine isothiocyanate-labeled concanavalin A (TRITC-Con A) with fluorescence and confocal microscopy. In the presence of insulin, or 24 h after insulin pretreatment (hormonal imprinting), the binding and uptake of TRITC-Con A increased when compared to controls, owing to the binding of TRITC-Con A to sugar oligomers of insulin receptors. Mannose inhibited the binding of Con A, thus demonstrating the specificity of binding. Histamine, a phagocytosis-promoting factor in mammals and Tetrahymena, and galactose, did not influence the uptake of TRITC-Con A.

  10. Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

    USGS Publications Warehouse

    Rattner, B.A.; Michael, S.D.

    1985-01-01

    Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

  11. Protective Role of Endogenous Ovarian Hormones Against Learning and Memory Impairments and Brain Tissues Oxidative Damage Induced by Lipopolysaccharide

    PubMed Central

    Pourganji, Masoume; Hosseini, Mahmoud; Soukhtanloo, Mohammad; Zabihi, Hoda; Hadjzadeh, Mosa Al-reza

    2014-01-01

    Background: The contribution of neuroinflammation in Alzheimer’s disease (AD) has been widely reported. The effects of female gonadal hormones in both neuroinflammation and brain cognitive functions have also been well considered. Objectives: In the present study, the possible protective role for endogenous ovarian hormones against learning and memory impairment as well as brain tissues oxidative damage induced by lipopolysachride (LPS) was investigated in rats. Materials and Methods: The rats were divided into four groups: Sham-LPS, Ovariectomized (OVX)-LPS, Sham, and OVX. The animals of sham group were in proestrous phase in which the serum concentration of estradiol is high. The Sham-LPS and OVX-LPS groups were treated with LPS (250 µg/kg) before acquisition. The animals were examined using passive avoidance (PA) test. The brains were then removed and malondialdehyde (MDA) and total thiol groups concentrations were measured. Results: The time latency to enter the dark compartment by OVX-LPS group was shorter than that of OVX at both first and 24th hours after the shock (P < 0.05 - P < 0.001). In Sham-LPS and OVX-LPS groups, total thiol concentration in hippocampal and cortical tissues were significantly lower while MDA concentrations were higher than that of Sham and OVX groups (P < 0.05 - P < 0.001). ). The hippocampal MDA concentration in OVX-LPS group was higher than Sham- LPS group (P < 0.01). Conclusions: Brain tissue oxidative damage contributed in deleterious effects of LPS on learning and memory. Some protective effects for the endogenous ovarian hormones against damaging effects of LPS on learning and memory function, as well as brain tissues oxidative damage could be postulated; however, it needs more investigation. PMID:24829769

  12. Expansion of specialized epidermis induced by hormonal state and mechanical strain.

    PubMed

    Wu, Hsin-Jung; Easwaran, Teresa; Offutt, Carlos D; Elgar, Richard Levi; Spandau, Dan F; Koyama, Sachiko; Foley, John

    2015-05-01

    In mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified. In the mouse, we observed a dramatic expansion of the specialized epidermis of the nipple, coupled to changes in connective tissue and hair shaft density, which we designate as areola formation. During this process thymidine analog uptake was elevated in the epidermis and hair follicles. Although there were no changes in connective tissue cell proliferation, we did observe an altered expression of extracellular matrix genes. In addition, the fibroblasts of the virgin nipple areola and region showed increased transcript and protein levels for estrogen, progesterone, relaxin, and oxytocin relative to those of ventral skin. To determine the role of pregnancy, lactation hormonal milieu, and localized mechanical strain on areola formation, we created models that separated these stimuli and evaluated changes in gross structure, proliferation and protein expression. While modest increases of epidermal proliferation and remodeling of connective tissue occurred as a result of individual stimuli, areola formation required exposure to pregnancy hormones, as well as mechanical strain.

  13. Role of estradiol in cortisol-induced reduction of luteinizing hormone pulse frequency.

    PubMed

    Oakley, Amy E; Breen, Kellie M; Tilbrook, Alan J; Wagenmaker, Elizabeth R; Karsch, Fred J

    2009-06-01

    Precise control of pulsatile GnRH and LH release is imperative to ovarian cyclicity but is vulnerable to environmental perturbations, like stress. In sheep, a sustained (29 h) increase in plasma cortisol to a level observed during stress profoundly reduces GnRH pulse frequency in ovariectomized ewes treated with ovarian steroids, whereas shorter infusion (6 h) is ineffective in the absence of ovarian hormones. This study first determined whether the ovarian steroid milieu or duration of exposure is the relevant factor in determining whether cortisol reduces LH pulse frequency. Prolonged (29 h) cortisol infusion did not lower LH pulse frequency in ovariectomized ewes deprived of ovarian hormones, but it did so in ovariectomized ewes treated with estradiol and progesterone to create an artificial estrous cycle, implicating ovarian steroids as the critical factor. Importantly, this effect of cortisol was more pronounced after the simulated preovulatory estradiol rise of the artificial follicular phase. The second experiment examined which component of the ovarian steroid milieu enables cortisol to reduce LH pulse frequency in the artificial follicular phase: prior exposure to progesterone in the luteal phase, low early follicular phase estradiol levels, or the preovulatory estradiol rise. Basal estradiol enabled cortisol to decrease LH pulse frequency, but the response was potentiated by the estradiol rise. These findings lead to the conclusion that ovarian steroids, particularly estradiol, enable cortisol to inhibit LH pulse frequency. Moreover, the results provide new insight into the means by which gonadal steroids, and possibly reproductive status, modulate neuroendocrine responses to stress.

  14. Dielectric screening of early differentiation patterns in mesenchymal stem cells induced by steroid hormones.

    PubMed

    Ron, Amit; Shur, Irena; Daniel, Ramiz; Singh, Ragini Raj; Fishelson, Nick; Croitoru, Nathan; Benayahu, Dafna; Shacham-Diamand, Yosi

    2010-06-01

    In the framework of this study, target identification and localization of differentiation patterns by means of dielectric spectroscopy is presented. Here, a primary pre-osteoblastic bone marrow-derived MBA-15 cellular system was used to study the variations in the dielectric properties of mesenchymal stem cells while exposed to differentiation regulators. Using the fundamentals of mixed dielectric theories combined with finite numerical tools, the permittivity spectra of MBA-15 cell suspensions have been uniquely analyzed after being activated by steroid hormones to express osteogenic phenotypes. Following the spectral analysis, significant variations were revealed in the dielectric properties of the activated cells in comparison to the untreated populations. Based on the differentiation patterns of MBA-15, the electrical modifications were found to be highly correlated with the activation of specific cellular mechanisms which directly react to the hormonal inductions. In addition, by describing the dielectric dispersion in terms of transfer functions, it is shown that the spectral perturbations are well adapted to variations in the electrical characteristics of the cells. The reported findings vastly emphasize the tight correlation between the cellular and electrical state of the differentiated cells. It therefore emphasizes the vast abilities of impedance-based techniques as potential screening tools for stem cell analysis.

  15. Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.

    PubMed

    Yoneda, Masashi; Goto, Manabu; Nakamura, Kimihide; Shimada, Tadahito; Hiraishi, Hideyuki; Terano, Akira; Haneda, Masakazu

    2005-02-15

    Central neuropeptides play a role in many physiological functions through the autonomic nervous system. We have recently demonstrated that central injection of a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow through vagal and nitric oxide-dependent pathways. In this study, the central effect of a TRH analog on experimental acute pancreatitis was investigated in rats. Acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5-100 ng), or saline was injected intracisternally 15 min before the first cerulein injection under ether anesthesia. Serum amylase level was measured before and 5 h after the first cerulein injection. Pancreatic wet/dry weight ratio and histological changes were also evaluated. Intracisternal TRH analog inhibited cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry weight ratio and pancreatic histological changes, such as interstitial edema, inflammation and vacuolization. The pancreatic cytoprotection induced by central TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine-methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous administration of the TRH analog did not influence cerulein-induced acute pancreatitis. These results indicate that the TRH analog acts in the central nervous system to protect against acute pancreatitis through vagal and nitric oxide-dependent pathways.

  16. Thymoquinone ameliorated elevated inflammatory cytokines in testicular tissue and sex hormones imbalance induced by oral chronic toxicity with sodium nitrite.

    PubMed

    Alyoussef, Abdullah; Al-Gayyar, Mohammed M H

    2016-07-01

    Scientific evidence illustrated the health hazards of exposure to nitrites for prolonged time. Nitrites affected several body organs due to oxidative, inflammatory and apoptosis properties. Furthermore, thymoquinone (TQ) had curative effects against many diseases. We tried to discover the impact of both sodium nitrite and TQ on inflammatory cytokines contents in testicular tissues and hormonal balance both in vivo and in vitro. Fifty adult male SD rats received 80mg/kg sodium nitrite and treated with either 25 or 50mg/kg TQ daily by oral-gavage for twelve weeks. Testis were removed for sperms' count. Testicular tissue homogenates were used for assessment of protein and gene expression of IL-1β, IL-6, TNF-α, Nrf2 and caspase-3. Serum samples were used for measurement of testosterone, LH, FSH and prolactin. Moreover, all the parameters were measured in human normal testis cell-lines, CRL-7002. Sodium nitrite produced significant decrease in serum testosterone associated with raised FSH, LH and prolactin. Moreover, sodium nitrite significantly elevated TNF-α, IL-1β, IL-6, caspase-3 and reduced Nrf2. TQ significantly reversed all these effects both in vivo and in vitro. In conclusion, TQ ameliorated testicular tissue inflammation and restored the normal balance of sex hormones induced by sodium nitrite both in vivo and in vitro.

  17. Glucoreceptors located in different areas mediate the hypoglycemia-induced release of growth hormone, prolactin, and adrenocorticotropin in man.

    PubMed

    Vigas, M; Tatár, P; Jurcovicová, J; Jezová, D

    1990-03-01

    In young male volunteers, the changes in growth hormone (GH), prolactin (PRL), and adrenocorticotropic hormone (ACTH) release in response to insulin injection combined with the infusion of saline, glucose, and fructose were evaluated. Glucose infusion in a dose which prevented insulin hypoglycemia completely abolished endocrine responses. Infusion of fructose, which is known not to cross the blood-brain barrier (BBB), did not influence the GH release during hypoglycemia; however, it inhibited PRL secretion. The ACTH response was slightly attenuated and delayed, while the hypoglycemia-induced rise in cortisol levels was not modified by fructose infusion. These data indicate that the glucoreceptors mediating the signals for a complete counterregulatory neuroendocrine response are not located in a single brain structure. Stimuli for GH release are produced in areas of the central nervous system protected by the BBB, while those for PRL release are presumably present in structures not protected by the BBB. Glucoreceptors triggering ACTH release are located both inside and outside the BBB.

  18. Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones.

    PubMed

    Gholap, S; Kar, A

    2003-06-01

    The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts either alone or in combination was evaluated in the amelioration of corticosteroid-induced hyperglycaemia in mice. Simultaneously thyroid hormone levels were estimated by radio-immunoassay (RIA) in order to ascertain whether the effects are mediated through thyroid hormones or not. While the corticosteroid (dexamethasone) administration increased the serum glucose concentration, it decreased serum concentrations of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Administration of the two plant extracts either alone or in combination decreased the serum glucose concentration in dexamethasone induced hyperglycaemic animals. However, the administration of Inula racemosa and Gymnema sylvestre extracts in combination proved to be more effective than the individual extracts. These effects were comparable to a standard corticosteroid-inhibiting drug, ketoconazole. As no marked changes in thyroid hormone concentrations were observed by the administration of any of the plant extracts in dexamethasone treated animals, it is further suggested that these plant extracts may not prove to be effective in thyroid hormone mediated type II diabetes, but for steroid induced diabetes.

  19. Sex differences in stress-induced social withdrawal: independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding.

    PubMed

    Trainor, Brian C; Takahashi, Elizabeth Y; Campi, Katharine L; Florez, Stefani A; Greenberg, Gian D; Laman-Maharg, Abigail; Laredo, Sarah A; Orr, Veronica N; Silva, Andrea L; Steinman, Michael Q

    2013-03-01

    There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype.

  20. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    PubMed

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation.

  1. Re-evaluation of thyroid hormone signaling antagonism of tetrabromobisphenol A for validating the T3-induced Xenopus metamorphosis assay.

    PubMed

    Wang, Yao; Li, Yuanyuan; Qin, Zhanfen; Wei, Wuji

    2017-02-01

    We developed the T3-induced Xenopus metamorphosis assay, which is supposed to be able to sensitively detect thyroid hormone (TH) signaling disruption of chemicals. The present study aimed to validate the T3-induced Xenopus metamorphosis assay by re-evaluating the TH signaling antagonism of tetrabromobisphenol A (TBBPA), a known TH signaling disruptor. According to the assay we developed, Xenopus tadpoles at stage 52 were exposed to 10-500nmol/L TBBPA in the presence of 1nmol/L T3. After 96hr of exposure, TBBPA in the range of 10-500nmol/L was found to significantly inhibit T3-induced morphological changes of Xenopus tadpoles in a concentration-dependent manner in term of body weight and four morphological endpoints including head area (HA), mouth width (MW), unilateral brain width/brain length (ULBW/BL), and hind-limb length/snout-vent length (HLL/SVL). The results show that these endpoints we developed are sensitive for characterizing the antagonistic effects of TBBPA on T3-induced metamorphosis. Following a 24-hr exposure, we found that TBBPA antagonized expression of T3-induced TH-response genes in the tail, which is consistent with previous findings in the intestine. We propose that the tail can be used as an alternative tissue to the intestine for examining molecular endpoints for evaluating TH signaling disruption. In conclusion, our results demonstrate that the T3-induced Xenopus metamorphosis assay we developed is an ideal in vivo assay for detecting TH signaling disruption.

  2. Glucose- and Hormone-Induced cAMP Oscillations in α- and β-Cells Within Intact Pancreatic Islets

    PubMed Central

    Tian, Geng; Sandler, Stellan; Gylfe, Erik; Tengholm, Anders

    2011-01-01

    OBJECTIVE cAMP is a critical messenger for insulin and glucagon secretion from pancreatic β- and α-cells, respectively. Dispersed β-cells show cAMP oscillations, but the signaling kinetics in cells within intact islets of Langerhans is unknown. RESEARCH DESIGN AND METHODS The subplasma-membrane cAMP concentration ([cAMP]pm) was recorded in α- and β-cells in the mantle of intact mouse pancreatic islets using total internal reflection microscopy and a fluorescent translocation biosensor. Cell identification was based on the opposite effects of adrenaline on cAMP in α- and β-cells. RESULTS In islets exposed to 3 mmol/L glucose, [cAMP]pm was low and stable. Glucagon and glucagon-like peptide-1(7-36)-amide (GLP-1) induced dose-dependent elevation of [cAMP]pm, often with oscillations synchronized among β-cells. Whereas glucagon also induced [cAMP]pm oscillations in most α-cells, <20% of the α-cells responded to GLP-1. Elevation of the glucose concentration to 11–30 mmol/L in the absence of hormones induced slow [cAMP]pm oscillations in both α- and β-cells. These cAMP oscillations were coordinated with those of the cytoplasmic Ca2+ concentration ([Ca2+]i) in the β-cells but not caused by the changes in [Ca2+]i. The transmembrane adenylyl cyclase (AC) inhibitor 2′5′-dideoxyadenosine suppressed the glucose- and hormone-induced [cAMP]pm elevations, whereas the preferential inhibitors of soluble AC, KH7, and 1,3,5(10)-estratrien-2,3,17-β-triol perturbed cell metabolism and lacked effect, respectively. CONCLUSIONS Oscillatory [cAMP]pm signaling in secretagogue-stimulated β-cells is maintained within intact islets and depends on transmembrane AC activity. The discovery of glucose- and glucagon-induced [cAMP]pm oscillations in α-cells indicates the involvement of cAMP in the regulation of pulsatile glucagon secretion. PMID:21444924

  3. Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate

    PubMed Central

    Dutta, Pinaki; Kumar, Santosh; Kakkar, Nandita; Bhansali, Anil; Rotondo, Fabio; Kovacs, Kalman

    2014-01-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH. PMID:24818037

  4. Richter's Syndrome with Hypercalcemia Induced by Tumor-Associated Production of Parathyroid Hormone-Related Peptide

    PubMed Central

    Watanabe, Naoki; Yasuda, Hajime; Morishita, Soji; Aota, Yasuo; Tomomatsu, Junichi; Tanaka, Masaru; Ohsaka, Akimichi; Komatsu, Norio

    2017-01-01

    Humoral hypercalcemia due to parathyroid hormone-related peptide (PTHrP) elevation is a well-known complication of various malignancies, but the situation is rare concerning hematological malignancies except for adult T-cell leukemia/lymphoma. We report a case of Richter's syndrome with humoral hypercalcemia, and demonstrate by reverse transcription polymerase chain reaction (RT-PCR) that peripheral blood PTHrP levels were 2,500-fold higher compared to healthy controls. PTHrP production by tumor cells in chronic lymphocytic leukemia (CLL) and Richter's syndrome has been previously demonstrated by nonquantitative methods such as immunohistochemistry and northern blot analysis, but this is the first report using the RT-PCR method. The presented case did not have hypercalcemia when initially diagnosed as small lymphocytic lymphoma (SLL), and as reported earlier, the development of hypercalcemia may be an indication of the transformation to Richter's syndrome in patients with CLL/SLL. PMID:28203174

  5. Persistent hiccups in cancer patient: a presentation of syndrome of inappropriate antidiuretic hormone induced hyponatremia.

    PubMed

    Goyal, Alka; Mehmood, Syed; Mishra, Seema; Bhatnagar, Sushma

    2013-05-01

    Hyponatremia is quite common in cancer patients, but the presentation as persistent hiccups is not common. Literature over hiccups development due to hyponatremia is quite scant. Hiccups are of various types, persistent hiccups are those that last more than 48 h and remains less than 1 month. Hiccups lasting more than 24 h require investigation for an underlying organic etiology, with hyponatremia included in the differential diagnosis. This paper discusses a carcinoma lip patient presented with the persistent hiccups and unconsciousness post-operatively. The patient was initially responded with trials of both metoclopramide and Ryle's tube insertion, but eventually, his hiccups resolved only after treatment of hyponatremia. Patient's clinical course and investigations suggest an etiology of syndrome of inappropriate antidiuretic hormone (SIADH) secretion behind the hyponatremia. Study suggested that SIADH linked hyponatremia should be considered in the differential diagnosis of cancer patients with refractory hiccups.

  6. Ultrastructural and hormonal changes in rat cauda epididymal spermatozoa induced by Boswellia papyrifera and Boswellia carterii.

    PubMed

    Ahmed, Mukhtar; Ali, Daoud; Harrath, Abdel Halim; Hussain, Tajamul; Al-Daghri, Nasser; Alokail, Majed S; Aladakatti, Ravindranath H; Ghodesawar, Mukhtar Ahmed G

    2014-04-01

    Boswellia papyrifera and Boswellia carterii diffuses smoke polluting air that adversely affects indoor environment that certainly harm human health. Therefore, this study aims at ascertaining the effect of these plants on gonadal hormones and molecular changes in rat spermatozoa. The animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily for 120 days along with suitable controls. Significant decreases in FSH, LH and testosterone levels were evidenced, along with a reduction of protein, sialic acid, and carnitine levels. In sperm physiology, sperm count, motility, speed decrease, whereas sperm anomalies increase. TEM observation indicates morphological changes in plasma and acrosomal membranes, cytoplasmic droplet in the tail region, vacuolated, and disorganization of the mitochondrial sheath. These findings demonstrate that B. papyrifera and B. carterii smoke affects the process of sperm formation and maturation, which indicates the detrimental effects of these plants on the reproductive system.

  7. Glucocorticoid hormone-induced chromatin remodeling enhances human hematopoietic stem cell homing and engraftment.

    PubMed

    Guo, Bin; Huang, Xinxin; Cooper, Scott; Broxmeyer, Hal E

    2017-03-06

    Efficient hematopoietic stem cell (HSC) homing is important for hematopoietic cell transplantation (HCT), especially when HSC numbers are limited, as in the use of cord blood (CB). In a screen of small-molecule compounds, we identified glucocorticoid (GC) hormone signaling as an activator of CXCR4 expression in human CB HSCs and hematopoietic progenitor cells (HPCs). Short-term GC pretreatment of human CB HSCs and HPCs promoted SDF-1-CXCR4-axis-mediated chemotaxis, homing, and long-term engraftment when these cells were transplanted into primary- and secondary-recipient NSG mice. Mechanistically, activated glucocorticoid receptor binds directly to a glucocorticoid response element in the CXCR4 promoter and recruits the SRC-1-p300 complex to promote H4K5 and H4K16 histone acetylation, facilitating transcription of CXCR4. These results suggest a new and readily available means to enhance the clinical efficacy of CB HCT.

  8. Hyper-G stress-induced hyperglycemia in rats mediated by glucoregulatory hormones

    NASA Technical Reports Server (NTRS)

    Daligcon, B. C.; Oyama, J.

    1985-01-01

    The present investigation is concerned with possible relations of the hyperglycemic response of rats exposed to hyper-G stress to (1) alterations in blood levels of the glucoregulatory hormones and gluconeogenic substrates, and (2) changes in insulin response on muscle glucose uptake. Male Sprague-Dawley rats weighing 250-300 g were used in the study. The results of the experiments indicate that the initial rapid rise in blood glucose of rats exposed to hyper-G stress is mediated by increases in circulating catecholamines and glucagon, both potent stimulators of hepatic gluconeogenesis. Lactate, derived from epinephrine stimulation of muscle glycogenolysis, appears to be a major precursor for the initial rise in blood glucose. The inhibition of the insulin-stimulated glucose uptake by muscle tissues may be a factor in the observed sustained hyperglycemia.

  9. Treatment for chemotherapy-induced alopecia in mice using parathyroid hormone agonists and antagonists linked to a collagen binding domain

    PubMed Central

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Suda, Hirofumi; Miyata, Shigeru; Sakon, Joshua; Matsushita, Osamu; Gensure, Robert C.

    2013-01-01

    Parathyroid hormone (PTH) agonists and antagonists have been shown to improve hair growth after chemotherapy; however, rapid clearance and systemic side-effects complicate their usage. To facilitate delivery and retention to skin, we fused PTH agonists and antagonists to the collagen binding domain (CBD) of Clostridium histolyticum collagenase. in-vitro studies showed that the agonist fusion protein, PTH-CBD, bound collagen and activated the PTH/parathyroid hormone-related peptide receptor in SaOS-2 cells. The antagonist fusion proteins, PTH(7–33)-CBD and PTH([−1]–33)-CBD, also bound collagen and antagonized PTH(1–34) effect in SaOS-2 cells; however, PTH(7–33)-CBD had lower intrinsic activity. Distribution studies confirmed uptake of PTH-CBD to the skin at 1 and 12 hr after subcutaneous injection. We assessed in vivo efficacy of PTH-CBD and PTH(7–33)-CBD in C57BL/6J mice. Animals were depilated to synchronize the hair follicles; treated on Day 7 with agonist, antagonist, or vehicle; treated on Day 9 with cyclophosphamide (150 mg/kg i.p.) or vehicle; and sacrificed on Day 39. Normal mice (no chemo and no treatment) showed rapid regrowth of hair and normal histology. Chemo + Vehicle mice showed reduced hair regrowth and decreased pigmentation; histology revealed reduced number and dystrophic anagen/catagen follicles. Chemo + Antagonist mice were grossly and histologically indistinguishable from Chemo + Vehicle mice. Chemo + Agonist mice showed more rapid regrowth and repigmentation of hair; histologically, there was a normal number of hair follicles, most of which were in the anagen phase. Overall, the agonist PTH-CBD had prominent effects in reducing chemotherapy-induced damage of hair follicles and may show promise as a therapy for chemotherapy-induced alopecia. PMID:22130912

  10. Role of sex hormones in hypercapnia-induced activation of the locus coeruleus in female and male rats.

    PubMed

    de Carvalho, D; Marques, D A; Bernuci, M P; Leite, C M; Araújo-Lopes, R; Anselmo-Franci, J; Bícego, K C; Szawka, R E; Gargaglioni, L H

    2016-01-28

    The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of the LC in hypercapnic ventilatory responses have been performed in males. Since ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 than males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in female and male rats with distinct sex hormone levels. Ovariectomized (OVX), estradiol (E2)-treated ovariectomized (OVX+E2) and female rats on the diestrous day of the estrous cycle were evaluated. Concurrently, males were investigated as gonad-intact, orchidectomized (ORX), testosterone (T)-treated ORX (ORX+T), and E2-treated ORX (ORX+E2). Activation of LC neurons was determined by double-label immunohistochemistry to c-Fos and tyrosine hydroxylase (TH). Hypercapnia induced by 7% CO2 increased the number of c-Fos/TH-immunoreactive (ir) neurons in the LC of all groups when compared to air exposure. Hypercapnia-induced c-Fos expression did not differ between diestrous females and intact male rats. In the OVX+E2 group, there was attenuation in the c-Fos expression during normocapnia compared with OVX rats, but CO2 responsiveness was not altered. Moreover, in ORX rats, neither T nor E2 treatments changed c-Fos expression in LC noradrenergic neurons. Thus, in female rats, E2 reduces activation of LC noradrenergic neurons, whereas in males, sex hormones do not influence the LC activity.

  11. Photoperiod regulation of plasma growth hormone levels during induced smoltification of underyearling Atlantic salmon.

    PubMed

    Björnsson, B T; Hemre, G I; Bjørnevik, M; Hansen, T

    2000-07-01

    Earlier studies have established that increased daylength increases plasma growth hormone (GH) levels during spring smoltification of yearling Atlantic salmon. Recently, the Atlantic salmon aquaculture industry has started the production of underyearling ("summer") smolts. This involves fast juvenile growth on continuous light (24L), the transfer of juveniles over 8 cm in length to short day (12L) for 6 weeks in the summer, followed by transfer to 24L for another 6 weeks before transfer to seawater in late October. Three groups were studied in fresh water from July to the following May in order to elucidate the GH response to this photoperiod manipulation: one group was kept on 24L throughout (long-day group), while the other two groups were exposed to short day from July 15th. Of these, one was brought back onto long day on September 1st (winter group) while the other was kept on short day (short-day group). Plasma GH levels of the long-day group were around 1.6 ng/ml throughout the study. The short-day transfer suppressed GH levels to 0.7 ng/ml within 2 weeks (short-day and winter groups). The long-day transfer (winter group) increased GH levels to 11 ng/ml within 3 weeks, and this elevation of GH levels was sustained for about 3 months, before declining to pretreatment levels. The study demonstrates that underyearling Atlantic salmon react to increased daylength in a way similar to traditional yearling smolts. It also demonstrates for the first time that decreased daylength can suppress plasma GH levels in fish. It is concluded that winter photoperiod manipulation causes an out-of-season initiation and completion of the parr-smolt transformation of underyearling Atlantic salmon and that growth hormone plays a major role in this process.

  12. Catechin induced modulation in the activities of thyroid hormone synthesizing enzymes leading to hypothyroidism.

    PubMed

    Chandra, Amar K; De, Neela

    2013-02-01

    Catechins, the flavonoids found in abundance in green tea, have many beneficial health effects such as antioxidative, anticarcinogenic, anti-inflammatory, antiallergic, and hypotensive properties. However, flavonoids have antithyroid/goitrogenic effect, although less information is available about the effect of pure catechin on thyroid physiology. The present investigation has been undertaken to explore the effect of catechin administration on thyroid physiology in rat model. For the in vivo experiment catechin was injected intraperitoneally (i.p.) at doses of 10, 20 and 30 mg/kg body to male albino rats for 15 and 30 days, respectively, and thyroid activities were evaluated with respect to determination of serum levels of thyroid hormones, thyroid peroxidase, 5'-deiodinase I (5'-DI), and Na(+), K(+)-ATPase activities that are involved in the synthesis of thyroid hormone. Catechin decreased the activities of thyroid peroxidase and thyroidal 5'-deiodinase I, while Na(+), K(+)-ATPase activity significantly increased in dose-dependent manner; substantial decrease in serum T3 and T4 levels coupled with significant elevation of serum TSH were also noted. Histological examinations of the thyroid gland revealed marked hypertrophy and/or hyperplasia of the thyroid follicles with depleted colloid content. In in vitro study, short-term exposure of rat thyroid tissue to catechin at the concentrations of 0.10, 0.20, and 0.30 mg/ml leads to decrease in the activities of thyroid peroxidase and 5'-deiodinase I, while the activity of thyroidal Na(+), K(+)-ATPase remains unaltered even at high concentration of catechin treatment. The present study reinforces the concept that catechin, tea flavonoids possess potent antithyroid activity as evidenced from in vivo and in vitro studies.

  13. Defense Responses in Aspen with Altered Pectin Methylesterase Activity Reveal the Hormonal Inducers of Tyloses1[OPEN

    PubMed Central

    Leśniewska, Joanna; Krzesłowska, Magdalena; Kushwah, Sunita; Sundberg, Björn; Moritz, Thomas

    2017-01-01

    Tyloses are ingrowths of parenchyma cells into the lumen of embolized xylem vessels, thereby protecting the remaining xylem from pathogens. They are found in heartwood, sapwood, and in abscission zones and can be induced by various stresses, but their molecular triggers are unknown. Here, we report that down-regulation of PECTIN METHYLESTERASE1 (PtxtPME1) in aspen (Populus tremula × tremuloides) triggers the formation of tyloses and activation of oxidative stress. We tested whether any of the oxidative stress-related hormones could induce tyloses in intact plantlets grown in sterile culture. Jasmonates, including jasmonic acid (JA) and methyl jasmonate, induced the formation of tyloses, whereas treatments with salicylic acid (SA) and 1-aminocyclopropane-1-carboxylic acid (ACC) were ineffective. SA abolished the induction of tyloses by JA, whereas ACC was synergistic with JA. The ability of ACC to stimulate tyloses formation when combined with JA depended on ethylene (ET) signaling, as shown by a decrease in the response in ET-insensitive plants. Measurements of internal ACC and JA concentrations in wild-type and ET-insensitive plants treated simultaneously with these two compounds indicated that ACC and JA regulate each other’s concentration in an ET-dependent manner. The findings indicate that jasmonates acting synergistically with ethylene are the key molecular triggers of tyloses. PMID:27923986

  14. Hormone-induced cortical maturation ensures the slow block to polyspermy and does not couple with meiotic maturation in starfish.

    PubMed

    Hirohashi, Noritaka; Harada, Kaori; Chiba, Kazuyoshi

    2008-06-01

    Meiotic progression in starfish oocytes is reinitiated by a maturation-inducing hormone called 1-methyladenine (1-MeAde). In addition to meiotic maturation, 1-MeAde induces cortical maturation in which cortical granules become competent to discharge in response to fusion of a single sperm, which results in the formation of the fertilization envelope. We found that subthreshold concentrations of 1-MeAde induce cortical maturation without germinal vesicle breakdown (GVBD). During cortical maturation, the IP3 sensitivity of calcium stores was increased as well as during meiotic maturation. When oocytes were exposed with 1-MeAde only on a hemisphere of oocytes, the IP3 sensitivity of the cortical region was increased only in the exposed hemisphere, suggesting that signals and components involved in cortical maturation do not readily spread in the cytoplasm. Although a specific inhibitor of phosphatidylinositol-3 kinase, LY294002 blocked both GVBD and cortical maturation, a Cdc2 kinase inhibitor, roscovitine did not block cortical maturation. Inhibition of Akt activation by injecting the competitors for Akt phosphorylation and membrane recruitment also blocked cortical maturation. These results suggest that the signaling pathway leading to Akt activation is common in cortical maturation and meiotic maturation, and Cdc2 activation was not required for cortical maturation.

  15. Effects of extracerebral dopamine on salsolinol- or thyrotropin-releasing hormone-induced prolactin (PRL) secretion in goats.

    PubMed

    Inaba, Yuki; Kato, Yuki; Itou, Azumi; Chiba, Aoi; Sawai, Ken; Fülöp, Ferenc; Nagy, György Miklos; Hashizume, Tsutomu

    2016-12-01

    The aim of the present study was to clarify the effect of extracerebral dopamine (DA) on salsolinol (SAL)-induced prolactin (PRL) secretion in goats. An intravenous injection of SAL or thyrotropin-releasing hormone (TRH) was given to female goats before and after treatment with an extracerebral DA receptor antagonist, domperidone (DOM), and the PRL-releasing response to SAL was compared with that to TRH. DOM alone increased plasma PRL concentrations and the PRL-releasing response to DOM alone was greater than that to either SAL alone or TRH alone. The PRL-releasing response to DOM plus SAL was similar to that to DOM alone, and no additive effect of DOM and SAL on the secretion of PRL was observed. In contrast, the PRL-releasing response to DOM plus TRH was greater than that to either TRH alone or DOM alone and DOM synergistically increased TRH-induced PRL secretion. The present results demonstrate that the mechanism involved in PRL secretion by SAL differs from that by TRH, and suggest that the extracerebral DA might be associated in part with the modulation of SAL-induced PRL secretion in goats.

  16. Testicular Steroidogenesis and Locomotor Activity Are Regulated by Gonadotropin-Inhibitory Hormone in Male European Sea Bass

    PubMed Central

    Paullada-Salmerón, José A.; Cowan, Mairi; Aliaga-Guerrero, María; López-Olmeda, José F.; Mañanós, Evaristo L.; Zanuy, Silvia

    2016-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that suppresses reproduction by acting at both the brain and pituitary levels. In addition to the brain, GnIH may also be produced in gonads and can regulate steroidogenesis and gametogenesis. However, the function of GnIH in gonadal physiology has received little attention in fish. The main objective of this study was to evaluate the effects of peripheral sbGnih-1 and sbGnih-2 implants on gonadal development and steroidogenesis during the reproductive cycle of male sea bass (Dicentrarchus labrax). Both Gnihs decreased testosterone (T) and 11-ketotestosterone (11-KT) plasma levels in November and December (early- and mid-spermatogenesis) but did not affect plasma levels of the progestin 17,20β-dihydroxy-4-pregnen-3-one (DHP). In February (spermiation), fish treated with sbGnih-1 and sbGnih-2 exhibited testicles with abundant type A spermatogonia and partial spermatogenesis. In addition, we determined the effects of peripheral Gnih implants on plasma follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) levels, as well as on brain and pituitary expression of the main reproductive hormone genes and their receptors during the spermiation period (February). Treatment with sbGnih-2 increased brain gnrh2, gnih, kiss1r and gnihr transcript levels. Whereas, both Gnihs decreased lhbeta expression and plasma Lh levels, and sbGnih-1 reduced plasmatic Fsh. Finally, through behavioral recording we showed that Gnih implanted animals exhibited a significant increase in diurnal activity from late spermatogenic to early spermiogenic stages. Our results indicate that Gnih may regulate the reproductive axis of sea bass acting not only on brain and pituitary hormones but also on gonadal physiology and behavior. PMID:27788270

  17. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones.

    PubMed

    Peeling, Peter; Dawson, Brian; Goodman, Carmel; Landers, Grant; Trinder, Debbie

    2008-07-01

    Iron is utilised by the body for oxygen transport and energy production, and is therefore essential to athletic performance. Commonly, athletes are diagnosed as iron deficient, however, contrasting evidence exists as to the severity of deficiency and the effect on performance. Iron losses can result from a host of mechanisms during exercise such as hemolysis, hematuria, sweating and gastrointestinal bleeding. Additionally, recent research investigating the anemia of inflammation during states of chronic disease has allowed us to draw some comparisons between unhealthy populations and athletes. The acute-phase response is a well-recognised reaction to both exercise and disease. Elevated cytokine levels from such a response have been shown to increase the liver production of the hormone Hepcidin. Hepcidin up-regulation has a negative impact on the iron transport and absorption channels within the body, and may explain a potential new mechanism behind iron deficiency in athletes. This review will attempt to explore the current literature that exits in this new area of iron metabolism and exercise.

  18. Hormonal contraceptives suppress oxytocin-induced brain reward responses to the partner's face.

    PubMed

    Scheele, Dirk; Plota, Jessica; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

    2016-05-01

    The hypothalamic peptide oxytocin (OXT) has been identified as a key modulator of pair-bonding in men, but its effects in women are still elusive. Moreover, there is substantial evidence that hormonal contraception (HC) influences partner preferences and sexual satisfaction, which constitute core domains of OXT function. We thus hypothesized that OXT effects on partner-related behavioral and neural responses could be significantly altered in women using HC. In this functional magnetic resonance imaging study involving 40 pair-bonded women, 21 of whom were using HC, we investigated whether a 24-IU nasal dose of OXT would modulate brain reward responses evoked by the romantic partner's face relative to the faces of familiar and unfamiliar people. Treatment with OXT increased the perceived attractiveness of the partner relative to other men, which was paralleled by elevated responses in reward-associated regions, including the nucleus accumbens. These effects of OXT were absent in women using HC. Our results confirm and extend previous findings in men that OXT interacts with the brain reward system to reinforce partner value representations, indicating a common OXT-dependent mechanism underlying partner attraction in both sexes. This mechanism may be disturbed in women using HC, suggesting that gonadal steroids could alter partner-specific OXT effects.

  19. Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis.

    PubMed

    Kaur, Jaspinder; Kumar, Dileep; Alfishawy, Mostafa; Lopez, Ricardo; Sachmechi, Issac

    2016-01-01

    Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH), neuroleptic malignant syndrome (NMS), and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK) and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone.

  20. High-Dose Risperidone Induced Latent Syndrome of Inappropriate Antidiuretic Hormone Secretion With Seizure Presentation.

    PubMed

    Lee, Yen-Feng; Tsai, Chia-Kuang; Liang, Chih-Sung

    2015-01-01

    We report a case of a patient with schizophrenia treated with high-dose risperidone, who developed syndrome of inappropriate antidiuretic hormone secretion (SIADH) with the only early symptom of tonic-clonic seizures. A 40-year-old woman with schizophrenia was treated with risperidone 2 mg/d. After the dosage was titrated to 6 mg/d, she experienced generalized seizure attacks. Laboratory screening revealed that the serum sodium level was 106 mmol/L, the urine sodium concentration was 41.2 mmol/L, and the urine osmolality was 371 mOsm/kg H2O. A diagnosis of SIADH was made, and risperidone was stopped. After infusion of hypertonic saline, the serum sodium returned to normal levels, and seizures did not recur. In this patient, SIADH advanced in a latent manner because the first and only symptom of SIADH was seizure attack. High-dose risperidone treatment is the most probable cause, and the mechanisms may be related to risperidone's high affinity for the 5-hydroxytryptamine 2A and dopamine 2 receptors. Patients with schizophrenia can display atypical features of medical illnesses. Routine physical and laboratory examinations may prevent silent disease progression.

  1. Paliperidone Inducing Concomitantly Syndrome of Inappropriate Antidiuretic Hormone, Neuroleptic Malignant Syndrome, and Rhabdomyolysis

    PubMed Central

    Lopez, Ricardo

    2016-01-01

    Paliperidone, an active metabolite of risperidone, is a new atypical antipsychotic agent. Syndrome of inappropriate antidiuretic hormone (SIADH), neuroleptic malignant syndrome (NMS), and rhabdomyolysis are the uncommon side effects of psychotropic drugs. We report a case of 35-year-old male with schizoaffective disorder who was admitted for acute-on-chronic exacerbation of his psychotic disorder for which intramuscular paliperidone 234 mg injection was given. Two days later, the patient developed hyponatremic seizures secondary to SIADH which was treated with hypertonic saline. On the third day, he developed high grade fever and severe muscle rigidity with raised creatine phosphokinase (CPK) and liver enzymes levels. He was treated with dantrolene 100 mg, bromocriptine 2.5 mg, and lorazepam 2 mg. Our patient required management of the three rare conditions following treatment with paliperidone. This case highlights the need for health care providers to be aware of the rare, potentially life threatening but preventable hyponatremia, NMS, and rhabdomyolysis as a possible adverse effect of paliperidone. PMID:27721999

  2. Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate.

    PubMed

    Ohlsson, C; Nilsson, A; Isaksson, O; Lindahl, A

    1992-10-15

    To study the effect of locally infused growth hormone (GH) or insulin-like growth factor I(IGF-I) on slowly cycling cells in the germinal cell layer of the tibial growth plate, osmotic minipumps delivering 14.3 microCi of [3H]thymidine per day were implanted s.c. into hypophysectomized rats, and GH (1 microgram) or IGF-I (10 micrograms) was injected daily through a cannula implanted in the proximal tibia. The opposite leg served as a control. After 12 days of treatment, the osmotic minipumps were removed, and three rats in each group were given GH (20 micrograms/day, s.c.) for an additional 14 days to chase the labeled cells out of the proliferative layers. Labeled cells remained in the germinal layer, in the perichondrial ring, and on the surface of the articular cartilage close to the epiphyseal plate. GH administered together with labeled thymidine significantly increased the number of labeled cells in the germinal cell layer compared to that in the control leg (ratio = 1.95 +/- 0.13), whereas IGF-I showed no stimulatory effect (ratio = 0.96 +/- 0.04). Therefore GH but not IGF-I stimulates the multiplication of the slowly cycling (label-retaining) cells in the germinal layer of the epiphyseal plate. IGF-I acts only on the proliferation of the resulting chondrocytes.

  3. Melanin concentrating hormone induces hippocampal acetylcholine release via the medial septum in rats.

    PubMed

    Lu, Zhi-Hong; Fukuda, Satoru; Minakawa, Yoichi; Yasuda, Atsushi; Sakamoto, Hidetoshi; Sawamura, Shigehito; Takahashi, Hidenori; Ishii, Noriko

    2013-06-01

    Among various actions of melanin concentrating hormone (MCH), its memory function has been focused in animal studies. Although MCH neurons project to various areas in the brain, one main target site of MCH is hippocampal formation for memory consolidation. Recent immunohistochemical study shows that MCH neurons directly project to the hippocampal formation and may indirectly affect the hippocampus through the medial septum nucleus (MS). It has been reported that sleep is necessary for memory and that hippocampal acetylcholine (ACh) release is indispensable for memory consolidation. However, there is no report how MCH actually influences the hippocampal ACh effluxes in accordance with the sleep-wake cycle changes. Thus, we investigated the modulatory function of intracerebroventricular (icv) injection of MCH on the sleep-wake cycle and ACh release using microdialysis techniques. Icv injection of MCH significantly increased the rapid eye movement (REM) and non-REM episode time and the hippocampal, not cortical, ACh effluxes. There was a significant correlation between REM episode time and hippocampal ACh effluxes, but not between REM episode time and cortical ACh effluxes. Microinjection of MCH into the MS increased the hippocampal ACh effluxes with no influence on the REM episode time. It appears that the effect sites of icv MCH for prolongation of REM episode time may be other neuronal areas than the cholinergic neurons in the MS. We conclude that MCH actually increases the hippocampal ACh release at least in part through the MS in rats.

  4. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    PubMed

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  5. Distribution and responsiveness of rat anti-Muellerian hormone during ovarian development and VCD-induced ovotoxicity

    SciTech Connect

    Mark-Kappeler, Connie J.; Sen, Nivedita; Keating, Aileen F.; Sipes, I. Glenn; Hoyer, Patricia B.

    2010-11-15

    Anti-Muellerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 {mu}M, 2-8 days) decreased (P < 0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days {+-} VCD (30 {mu}M) caused an increase (P < 0.05) in primordial, and a decrease (P < 0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

  6. 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.

  7. Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity.

    PubMed

    Mark-Kappeler, Connie J; Sen, Nivedita; Keating, Aileen F; Sipes, I Glenn; Hoyer, Patricia B

    2010-11-15

    Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 μM, 2-8 days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days±VCD (30 μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

  8. Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

    NASA Astrophysics Data System (ADS)

    Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

    2006-07-01

    Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

  9. Uniconazole-induced tolerance of soybean to water deficit stress in relation to changes in photosynthesis, hormones and antioxidant system.

    PubMed

    Zhang, Mingcai; Duan, Liusheng; Tian, Xiaoli; He, Zhongpei; Li, Jianmin; Wang, Baomin; Li, Zhaohu

    2007-06-01

    This study investigated whether uniconazole confers drought tolerance to soybean and if such tolerance is correlated with changes in photosynthesis, hormones and antioxidant system of leaves. Soybean plants were foliar treated with uniconazole at 50 mg L-1 at the beginning of bloom and then exposed to water deficit stress at pod initiation for 7 d. Uniconazole promoted biomass accumulation and seed yield under both water conditions. Plants treated with uniconazole showed higher leaf water potential only in water-stressed condition. Water stress decreased the chlorophyll content and photosynthetic rate, but those of uniconazole-treated plants were higher than the stressed control. Uniconazole increased the maximum quantum yield of photosystemand ribulose-1,5-bisphosphate carboxylase/oxygenase activity of water-stressed plants. Water stress decreased partitioning of assimilated 14C from labeled leaf to the other parts of the plant. In contrast, uniconazole enhanced translocation of assimilated 14C from labeled leaves to the other parts, except stems, regardless of water treatment. Uniconazole-treated plants contained less GA3, GA4 and ABA under well-watered condition than untreated plants, while the IAA and zeatin levels were increased substantially under both water conditions, and ABA concentration was also increased under water stressed condition. Under water-stressed conditions, uniconazole increased the content of proline and soluble sugars, and the activities of superoxide dismutase and peroxidase in soybean leaves but not the malondialdehyde content or electrical conductivity. These results suggest that uniconazole-induced tolerance to water deficit stress in soybean was related to the changes of photosynthesis, hormones and antioxidant system of leaves.

  10. Acute-onset hypomagnesemia-induced hypocalcemia caused by the refractoriness of bones and renal tubules to parathyroid hormone.

    PubMed

    Yamamoto, Masahiro; Yamaguchi, Toru; Yamauchi, Mika; Yano, Shozo; Sugimoto, Toshitsugu

    2011-11-01

    Chronic hypomagnesemia is closely associated with hypocalcemia, which is caused by impaired parathyroid hormone (PTH) secretion or the refractoriness of bone and renal tubules to PTH. The dominant mechanism of acute-onset, hypomagnesemia-induced hypocalcemia is currently unclear. An 83-year-old man who had undergone chemotherapy with carboplatin for prostate cancer suffered from acute diarrhea and finger paresthesia. Laboratory data confirmed hypocalcemia as well as hypomagnesemia. Urinary calcium levels were not measured. However, the urinary fractional excretion of Mg (FE(Mg)) was elevated. Despite elevated PTH levels, the renal tubular maximal reabsorption rate of phosphate to GFR (TmP/GFR) was elevated, and bone formation and resorption markers were suppressed. A magnesium loading test revealed a clear magnesium deficiency. After administration of magnesium, bone marker levels were increased, and TmP/GFR was reduced to normal levels, despite the persistent elevation of PTH. Serum calcium levels eventually increased to approximately the reference range. Clinical histories and these observations both suggest that when patients with hypomagnesemia-induced hypocalcemia rapidly lose magnesium through complications such as diarrhea, the primary cause may be the refractoriness of bone and renal tubules to PTH, rather than impaired PTH secretion.

  11. Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle.

    PubMed

    Alsted, Thomas J; Ploug, Thorkil; Prats, Clara; Serup, Annette K; Høeg, Louise; Schjerling, Peter; Holm, Cecilia; Zimmermann, Robert; Fledelius, Christian; Galbo, Henrik; Kiens, Bente

    2013-10-15

    In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for ∼98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.

  12. The phytopathogen Rhodococcus fascians breaks apical dominance and activates axillary meristems by inducing plant genes involved in hormone metabolism.

    PubMed

    Simón-Mateo, Carmen; Depuydt, Stephen; DE Oliveira Manes, Carmem Lara; Cnudde, Filip; Holsters, Marcelle; Goethals, Koen; Vereecke, Danny

    2006-03-01

    SUMMARY Rhodococcus fascians is a Gram-positive bacterium that interacts with many plant species and induces multiple shoots through a combination of activation of dormant axillary meristems and de novo meristem formation. Although phenotypic analysis of the symptoms of infected plants clearly demonstrates a disturbance of the phytohormonal balance and an activation of the cell cycle, the actual mechanism of symptom development and the targets of the bacterial signals are unknown. To elucidate the molecular pathways that are responsive to R. fascians infection, differential display was performed on Nicotiana tabacum as a host. Four differentially expressed genes could be identified that putatively encode a senescence-associated protein, a gibberellin 2-oxidase, a P450 monooxygenase and a proline dehydrogenase. The differential expression of the three latter genes was confirmed on infected Arabidopsis thaliana plants by quantitative reverse transcription polymerase chain reactions, supporting their general function in R. fascians-induced symptom development. The role of these genes in hormone metabolism, especially of gibberellin and abscisic acid, in breaking apical dominance and in activating axillary meristems, which are processes associated with symptom development, is discussed.

  13. Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle

    PubMed Central

    Alsted, Thomas J; Ploug, Thorkil; Prats, Clara; Serup, Annette K; Høeg, Louise; Schjerling, Peter; Holm, Cecilia; Zimmermann, Robert; Fledelius, Christian; Galbo, Henrik; Kiens, Bente

    2013-01-01

    In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for ∼98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions. PMID:23878361

  14. Sex Hormones Protect Against Amyloid-β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310.

    PubMed

    Costa, A R; Marcelino, H; Gonçalves, I; Quintela, T; Tomás, J; Duarte, A C; Fonseca, A M; Santos, C R A

    2016-09-01

    The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood on the basal side and the cerebrospinal fluid (CSF) on the apical side. It is a relevant source of many polypeptides secreted to the CSF with neuroprotective functions and also participates in the elimination and detoxification of brain metabolites, such as β-amyloid (Aβ) removal from the CSF through transporter-mediated influx. The CP is also a target tissue for sex hormones (SHs) that have recognised neuroprotective effects against a variety of insults, including Aβ toxicity and oxidative stress in the central nervous system. The present study aimed to understand how SHs modulate Aβ-induced oxidative stress in a CP cell line (Z310 cell line) by analysing the effects of Aβ1-42 on oxidative stress, mitochondrial function and apoptosis, as well as by assessing how 17β-oestradiol (E2 ) and 5α-dihydrotestosterone (DHT) modulated these effects and the cellular uptake of Aβ1-42 by CP cells. Our findings show that E2 and DHT treatment reduce Aβ1-42 -induced oxidative stress and the internalisation of Aβ1-42 by CP epithelial cells, highlighting the importance of considering the background of SHs and therefore sex-related differences in Aβ metabolism and clearance by CP cells.

  15. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men

    PubMed Central

    West, Daniel W D; Kujbida, Gregory W; Moore, Daniel R; Atherton, Philip; Burd, Nicholas A; Padzik, Jan P; De Lisio, Michael; Tang, Jason E; Parise, Gianni; Rennie, Michael J; Baker, Steven K; Phillips, Stuart M

    2009-01-01

    We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 ± 1.1 years, BMI = 26 ± 3.5 kg m−2) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF-1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 ± 0.007, LH = 0.071 ± 0.008, HH = 0.064 ± 0.014% h−1; P < 0.05) with no effect of elevated hormones (P= 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post-exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS. PMID:19736298

  16. Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development

    SciTech Connect

    Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L. . E-mail: clkeen@ucdavis.edu

    2006-09-01

    In experimental animals fed standard laboratory diets, penta-BDE mixtures can decrease circulating thyroid hormone and liver vitamin A concentrations. A substantial number of pregnant women and their children have marginal vitamin A status, potentially increasing their risk of adverse effects to penta-BDE exposure. The current study investigated the effects of maternal gestational and lactational penta-BDE exposure on thyroid hormone and vitamin A homeostasis in rats of sufficient vitamin A (VAS) or marginal vitamin A (VAM) status and their offspring. Dams were administered daily oral doses of 18 mg/kg DE-71 (a penta-BDE mixture) or a corn oil vehicle from gestation day 6 through lactation day (LD) 18. Thyroid hormone and vitamin A homeostasis were assessed in plasma and tissues of LD 19 dams and postnatal day (PND) 12, 18, and 31 pups. DE-71 exposure induced hepatomegaly in VAS and VAM pups at all timepoints and increased testes weights at PND 31. While liver vitamin A concentrations were low in DE-71 treated dams and pups, plasma retinol concentrations and plasma retinol binding protein levels were only low in VAM animals exposed to DE-71. DE-71 exposure lowered plasma thyroxine concentrations in VAS and VAM dams and pups. Plasma thyroid stimulating hormone concentrations were high in VAM dams exposed to DE-71, suggesting that marginal vitamin A status enhances the susceptibility to thyroid hormone axis disruption by DE-71. These results support the concept that marginal vitamin A status in pregnant women may increase the risk for PBDE-induced disruptions in vitamin A and thyroid hormone homeostasis.

  17. Role of progestin-induced mammary-derived growth hormone in the pathogenesis of cystic endometrial hyperplasia in the bitch.

    PubMed

    Bhatti, Sofie F M; Rao, Nagesha A S; Okkens, Auke C; Mol, Jan A; Duchateau, Luc; Ducatelle, Richard; van den Ingh, Ted S G A M; Tshamala, Mulenda; Van Ham, Luc M L; Coryn, Marc; Rijnberk, Ad; Kooistra, Hans S

    2007-10-01

    Endogenous progesterone and synthetic progestins may induce hypersecretion of growth hormone (GH) of mammary origin, hyperplastic ductular changes in the mammary gland, and the development of cystic endometrial hyperplasia (CEH) in dogs. It was investigated whether progestin-induced mammary GH plays a role in the pathogenesis of CEH in the bitch. During 1 year, bitches with surgically excised mammary glands and healthy control bitches received medroxyprogesterone acetate (MPA). Before and after MPA treatment, uterine and mammary tissues were collected for histological, immunohistochemical, and RT-PCR examination. After MPA administration, the mammary tissue in the control dogs had differentiated into lobulo-alveolar structures and CEH was present in all uteri of both dog groups. In the MPA-exposed mammary tissue of the control dogs, GH could only be demonstrated immunohistochemically in proliferating epithelium. After treatment with MPA the dogs of both groups had immunohistochemically demonstrable GH in the cytoplasm of hyperplastic glandular uterine epithelial cells. RT-PCR analysis of the mammary gland tissue after MPA administration demonstrated a significant higher GH gene, and lower GHR gene expression than before treatment. In the uterus, the expression of the gene encoding for GH was significantly increased in the mastectomized dogs, whereas in the control dogs the expression of the gene encoding for insulin-like growth factor-I had significantly increased with MPA administration. MPA treatment significantly down regulated PR gene expression in the uterus in both dog groups. These results indicate that progestin-induced GH of mammary origin is not an essential component in the development of CEH in the bitch.

  18. Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker

    USGS Publications Warehouse

    Yoshizaki, G.; Patino, R.; Thomas, P.; Bolamba, D.; Chang, Xiaotian

    2001-01-01

    A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown /maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker. ?? 2001 Elsevier Science.

  19. Intrathecal urocortin I in the spinal cord as a murine model of stress hormone-induced musculoskeletal and tactile hyperalgesia.

    PubMed

    Larson, Alice A; Nunez, Myra G; Kissel, Casey L; Kovács, Katalin J

    2015-11-01

    Stress is antinociceptive in some models of pain, but enhances musculoskeletal nociceptive responses in mice and muscle pain in patients with fibromyalgia syndrome. To test the hypothesis that urocortins are stress hormones that are sufficient to enhance tactile and musculoskeletal hyperalgesia, von Frey fibre sensitivity and grip force after injection of corticotropin-releasing factor (CRF), urocortin I and urocortin II were measured in mice. Urocortin I (a CRF1 and CRF2 receptor ligand) produced hyperalgesia in both assays when injected intrathecally (i.t.) but not intracerebroventricularly, and only at a large dose when injected peripherally, suggesting a spinal action. Morphine inhibited urocortin I-induced changes in nociceptive responses in a dose-related fashion, confirming that changes in behaviour reflect hyperalgesia rather than weakness. No tolerance developed to the effect of urocortin I (i.t.) when injected repeatedly, consistent with a potential to enhance pain chronically. Tactile hyperalgesia was inhibited by NBI-35965, a CRF1 receptor antagonist, but not astressin 2B, a CRF2 receptor antagonist. However, while urocortin I-induced decreases in grip force were not observed when co-administered i.t. with either NBI-35965 or astressin 2B, they were even more sensitive to inhibition by astressin, a non-selective CRF receptor antagonist. Together these data indicate that urocortin I acts at CRF receptors in the mouse spinal cord to elicit a reproducible and persistent tactile (von Frey) and musculoskeletal (grip force) hyperalgesia. Urocortin I-induced hyperalgesia may serve as a screen for drugs that alleviate painful conditions that are exacerbated by stress.

  20. Intrathecal Urocortin I in the spinal cord as a murine model of stress hormone-induced musculoskeletal and tactile hyperalgesia

    PubMed Central

    Larson, Alice A.; Nunez, Myra G.; Kissel, Casey L.; Kovács, Katalin J.

    2015-01-01

    Stress is antinociceptive in some models of pain but enhances musculoskeletal nociceptive responses in mice and muscle pain in patients with fibromyalgia syndrome. To test the hypothesis that urocortins are stress hormones that are sufficient to enhance tactile and musculoskeletal hyperalgesia, we measured von Frey fiber sensitivity and grip force after injection of corticotrophin releasing factor (CRF), urocortin I and urocortin II in mice. Urocortin I (a CRF1 and CRF2 receptor ligand) produced hyperalgesia in both assays when injected intrathecally (i.t.) but not intracerebroventricularly (i.c.v.), and only at a large dose when injected peripherally, suggesting a spinal action. Morphine inhibited urocortin I-induced changes in nociceptive responses in a dose-related fashion, confirming that changes in behavior reflect hyperalgesia rather than weakness. No tolerance developed to the effect of urocortin I (i.t.) when injected repeatedly, consistent with a potential to enhance pain chronically. Tactile hyperalgesia was inhibited by NBI-35965, a CRF1 receptor antagonist, but not astressin 2B, a CRF2 receptor antagonist. However, while urocortin I-induced decreases in grip force were not observed when coadministered i.t. with either NBI-35965 or astressin 2B, they were even more sensitive to inhibition by astressin, a nonselective CRF receptor antagonist. Together these data indicate that urocortin I acts at CRF receptors in the mouse spinal cord to elicit a reproducible and persistent tactile (von Frey) and musculoskeletal (grip force) hyperalgesia. Urocortin I-induced hyperalgesia may serve as a screen for drugs that alleviate painful conditions that are exacerbated by stress. PMID:26332847

  1. Hormonal and behavioural abnormalities induced by stress in utero: an animal model for depression.

    PubMed

    Maccari, S; Darnaudery, M; Van Reeth, O

    2001-09-01

    Prenatal stress in rats can exert profound influence on the off spring's development, inducing abnormalities such as increased "anxiety", "emotionality" or "depression-like" behaviours.Prenatal stress has long-term effects on the development of the hypothalamo-pituitary-adrenal(HPA) axis and forebrain cholinergic systems. These long-term neuroendocrinological effects are mediated, at least in part, by stress-induced maternal corticosterone increase during pregnancy and stress-induced maternal anxiety during the postnatal period. We have shown a significant phase advance in the circadian rhythms of corticosterone secretion and locomotor activity in prenatally-stressed (PNS) rats. When subjected to an abrupt shift in the light-dark(LD) cycle, PNS rats resynchronized their activity rhythm more slowly than control rats. In view of the data suggesting abnormalities in the circadian timing system in these animals, we have investigated the effects of prenatal stress on the sleep-wake cycle in adult male rats. PNS rats exhibited various changes in sleep-wake parameters, including a dramatic increase in the amount of paradoxical sleep. Taken together, our results indicate that prenatal stress can induce increased responses to stress and abnormal circadian rhythms and sleep in adult rats.Various clinical observations in humans suggest a possible pathophysiological link between depression and disturbances in circadian rhythmicity. Circadian abnormalities in depression can be related to those found in PNS rats. Interestingly, we have recently shown that the increased immobility in the forced swimming test observed in PNS rats can be corrected by chronic treatment with the antidepressant tianeptine, or with melatonin or S23478, a melatonin agonist. Those results reinforce the idea of the usefulness of PNS rats as an appropriate animal model to study human depression and support a new antidepressant-like effect of melatonin and the melatonin agonist S23478.

  2. Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes

    PubMed Central

    Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

    2013-01-01

    Background: The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Objective: Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Materials and Methods: Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. Results: The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Conclusion: Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This

  3. Natural Variation in Stress Hormones, Comparisons Across Matrices, and Impacts Resulting from Induced Stress in the Bottlenose Dolphin.

    PubMed

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E; Kellar, Nicholas M; Cockrem, John; Romano, Tracy; Booth, Rebecca K; Wasser, Samuel K

    2016-01-01

    Knowledge regarding stress hormones and how they vary in response to seasonality, gender, age, and reproductive status for any marine mammal is limited. Furthermore, stress hormones may be measured in more than one matrix (e.g., feces, blood, blubber), but the relationships between levels of a given hormone across these matrices are unknown, further complicating the interpretations of hormones measured in samples collected from wild animals. A study is underway to address these issues in a population of bottlenose dolphins trained for voluntary participation in sample collections from different matrices and across season and time of day.

  4. Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia

    PubMed Central

    Armitage, Andrew E.; Lim, Pei Jin; Frost, Joe N.; Pasricha, Sant-Rayn; Soilleux, Elizabeth J.; Evans, Emma; Morovat, Alireza; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Davies, Benjamin; Gileadi, Uzi; Robbins, Peter A.; Lakhal-Littleton, Samira; Drakesmith, Hal

    2016-01-01

    Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapidly accumulate iron and are susceptible to infection by blood-dwelling siderophilic bacteria such as Vibrio vulnificus. In order to study the innate immune role of hepcidin against a background of normal iron status, we developed a transgenic mouse model of tamoxifen-sensitive conditional Hamp1 deletion (termed iHamp1-KO mice). These mice attain adulthood with an iron status indistinguishable from littermate controls. Hamp1 disruption and the consequent decline of serum hepcidin concentrations occurred within hours of a single tamoxifen dose. We found that the TLR ligands LPS and Pam3CSK4 and heat-killed Brucella abortus caused an equivalent induction of inflammation in control and iHamp1-KO mice. Pam3CSK4 and B. abortus only caused a drop in serum iron in control mice, while hypoferraemia due to LPS was evident but substantially blunted in iHamp1-KO mice. Our results characterise a powerful new model of rapidly inducible hepcidin disruption, and demonstrate the critical contribution of hepcidin to the hypoferraemia of inflammation. PMID:27423740

  5. Regulation of hormone-induced Ca sup 2+ mobilization in the human platelets

    SciTech Connect

    Crouch, M.F.; Lapetina, E.G. )

    1990-03-01

    {alpha}-Thrombin, {gamma}-thrombin, and platelet-activating factor each stimulated the mobilization of intracellular Ca{sup 2+} stores in aspirin-treated human platelets. This was followed by desensitization of the receptors, as shown by the return of the Ca{sup 2+} level to basal values and by the fact that a subsequent addition of a second different agonist, but not the same agonist, could again elicit a response. Epinephrine, acting on {alpha}{sub 2}-adrenergic receptors, was by itself ineffective at mobilizing Ca{sup 2+} stores. However, when added after the thrombin-induced response, epinephrine could evoke a considerable release of Ca{sup 2+} from cellular stores. This appeared to be due to epinephrine recoupling thrombin receptors to phospholipase C. In support of this, epinephrine was able to induce the formation of inositol triphosphate when added after the response to thrombin had also become desensitized. Alone, epinephrine was without effect. Pre-activation of protein kinase C with the phorbol ester abolished these effects of epinephrine, suggesting that epinephrine was working by activating a protein which could be inactivated by phosphorylation. The current work is to characterize this protein that may be a member of the G{sub i}, GTP-binding protein family.

  6. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.

    PubMed

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

    2014-11-04

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

  7. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

    PubMed Central

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

    2014-01-01

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

  8. Hormonal implication in Bracon-venom-induced paralysation of the host larva of Corcyra cephalonica (Lepidoptera: Pyralidae).

    PubMed

    Chanda, Sudipta; Panda, R N; Chakravorty, Sanjib

    2002-08-01

    To facilitate oviposition, the ectoparasite Bracon hebetor, injects its venom, a paralysing toxin, to the host Corcyra larva that ultimately dies without showing any metamorphic change, even if allowed to remain unparasitised. At the initial stage of venom injection the rate of heartbeat of the host becomes abruptly high. This has been explained from the synergistic action of the substances of poison gland and calyx. The paralysed larvae subsequent to envenomization die within 240 hr. Application of hydroprene as single dose or with a booster dose after paralysation mostly increases the survival period considering heart beat as the index. The predicted value of survival period (714.4 hr), determined from a fitted equation obtained from the relationship between heart beat and survival period, indicates that a 100 microg treatment/larva with a booster dose of 50 microg/larva most effectively lengthens the period. It is concluded that the venom-induced physiological dysfunction of the immobilised larvae, as indicated in the rate of heart beat and survival period, though can be recovered to some extent after the application of juvenoids, there cannot occur any metamorphic change of these larvae. The parasitoid, therefore, succeeds in completing its development and metamorphosis by arresting the development of its host through an indirect hormonal suppression. The findings indicate an endocrine implication in host-parasite relationship in insect.

  9. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

    PubMed

    Clark, Erica S; Flannery, Brenna M; Gardner, Elizabeth M; Pestka, James J

    2015-10-19

    Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  10. A novel subtilisin-like serine protease of Batrachochytrium dendrobatidis is induced by thyroid hormone and degrades antimicrobial peptides.

    PubMed

    Thekkiniath, Jose C; Zabet-Moghaddam, Masoud; San Francisco, Susan K; San Francisco, Michael J

    2013-06-01

    Batrachochytrium dendrobatidis (B. dendrobatidis), a chytrid fungus, is one of the major contributors to the global amphibian decline. The fungus infects both tadpoles and adult amphibians. Tadpoles are infected in their keratinized mouthparts, and infected adults exhibit hyperkeratosis and loss of righting reflex. Infections of adults may result in death from cardiac arrest in susceptible species. Thyroid hormone plays a key role in amphibian metamorphosis. The occurrence of B. dendrobatidis in tadpoles during metamorphosis may result in exposure of the fungus to host morphogens including TH. This exposure may induce gene expression in the fungus contributing to invasion and colonization of the host. Here, we demonstrate movement of fungal zoospores toward TH. Additionally, expression of a subtilisin-like serine protease is up-regulated in B. dendrobatidis cells exposed to TH. A gene encoding this protease was cloned from B. dendrobatidis and expressed in Escherichia coli. The protein was partially purified and characterized. The similarity between subtilases of human dermatophytes and the B. dendrobatidis subtilisin-like serine protease suggests the importance of this enzyme in B. dendrobatidis pathogenicity. Cleavage of frog skin antimicrobial peptides (AMPs) by this B. dendrobatidis subtilisin-like serine protease suggests a role for this enzyme in fungal survival and colonization.

  11. Growth hormone improves growth retardation induced by rapamycin without blocking its antiproliferative and antiangiogenic effects on rat growth plate.

    PubMed

    Álvarez-García, Óscar; García-López, Enrique; Loredo, Vanessa; Gil-Peña, Helena; Mejía-Gaviria, Natalia; Rodríguez-Suárez, Julián; Ordóñez, Flor Á; Santos, Fernando

    2012-01-01

    Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis.

  12. Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.

    PubMed

    Gaspers, Lawrence D; Bartlett, Paula J; Politi, Antonio; Burnett, Paul; Metzger, Walson; Johnston, Jane; Joseph, Suresh K; Höfer, Thomas; Thomas, Andrew P

    2014-11-20

    Receptor-mediated oscillations in cytosolic Ca(2+) concentration ([Ca(2+)]i) could originate either directly from an autonomous Ca(2+) feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca(2+) feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca(2+) oscillations or could just be a secondary response to the [Ca(2+)]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state [IP3]. GFP-LBD perturbed [Ca(2+)]i oscillations in a dose-dependent manner: it decreased both the rate of [Ca(2+)]i rise and the speed of Ca(2+) wave propagation and, at high levels, abolished [Ca(2+)]i oscillations completely. These data, together with computational modeling, demonstrate that IP3 dynamics play a fundamental role in generating [Ca(2+)]i oscillations and waves.

  13. Growth Hormone Improves Growth Retardation Induced by Rapamycin without Blocking Its Antiproliferative and Antiangiogenic Effects on Rat Growth Plate

    PubMed Central

    Álvarez-García, Óscar; García-López, Enrique; Loredo, Vanessa; Gil-Peña, Helena; Mejía-Gaviria, Natalia; Rodríguez-Suárez, Julián; Ordóñez, Flor Á.; Santos, Fernando

    2012-01-01

    Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis. PMID:22493717

  14. Oleic acid induces specific alterations in the morphology, gene expression and steroid hormone production of cultured bovine granulosa cells.

    PubMed

    Yenuganti, Vengala Rao; Viergutz, Torsten; Vanselow, Jens

    2016-06-01

    After parturition, one of the major problems related to nutritional management that is faced by the majority of dairy cows is negative energy balance (NEB). During NEB, excessive lipid mobilization takes place and hence the levels of free fatty acids, among them oleic acid, increase in the blood, but also in the follicular fluid. This accumulation can be associated with serious metabolic and reproductive disorders. In the present study, we analyzed the effects of physiological concentrations of oleic acid on cell morphology, apoptosis, necrosis, proliferation and steroid production, and on the abundance of selected transcripts in cultured bovine granulosa cells. Increasing oleic acid concentrations induced intracellular lipid droplet accumulation, thus resulting in a foam cell-like morphology, but had no effects on apoptosis, necrosis or proliferation. Oleic acid also significantly reduced the transcript abundance of the gonadotropin hormone receptors, FSHR and LHCGR, steroidogenic genes STAR, CYP11A1, HSD3B1 and CYP19A1, the cell cycle regulator CCND2, but not of the proliferation marker PCNA. In addition, treatment increased the transcript levels of the fatty acid transporters CD36 and SLC27A1, and decreased the production of 17-beta-estradiol and progesterone. From these data it can be concluded that oleic acid specifically affects morphological and physiological features and gene expression levels thus altering the functionality of granulosa cells. Suggestively, these effects might be partly due to the reduced expression of FSHR and thus the reduced responsiveness to FSH stimulation.

  15. The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells.

    PubMed

    Maltese, Giuseppe; Psefteli, Paraskevi-Maria; Rizzo, Benedetta; Srivastava, Salil; Gnudi, Luigi; Mann, Giovanni E; Siow, Richard C M

    2017-03-01

    Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated. AngII contributes to vascular ageing and atherogenesis by enhancing VSMC oxidative stress, senescence and apoptosis. This study demonstrates that soluble klotho (1 nM, 24 hrs) significantly induces expression of Nrf2 and the antioxidant enzymes haeme oxygenase (HO-1) and peroxiredoxin-1 (Prx-1) and enhances glutathione levels in human aortic smooth muscle cells (HASMC). Silencing of Nrf2 attenuated the induction of HO-1 and Prx-1 expression by soluble klotho. Furthermore, soluble klotho protected against AngII-mediated HASMC apoptosis and senescence via activation of Nrf2. Thus, our findings highlight a novel Nrf2-mediated mechanism underlying the protective actions of soluble klotho in HAMSC. Targeting klotho may thus represent a therapeutic strategy against VSMC dysfunction and cardiovascular ageing.

  16. Induction of T(4) UDP-GT activity, serum thyroid stimulating hormone, and thyroid follicular cell proliferation in mice treated with microsomal enzyme inducers.

    PubMed

    Hood, Alan; Allen, Marcia L; Liu, YaPing; Liu, Jie; Klaassen, Curtis D

    2003-04-01

    The microsomal enzyme inducers phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are known to induce thyroxine (T(4)) glucuronidation and reduce serum T(4) concentrations in rats. Also, microsomal enzyme inducers that increase serum TSH (i.e., PB and PCN) also increase thyroid follicular cell proliferation in rats. Little is known about the effects of these microsomal enzyme inducers on T(4) glucuronidation, serum thyroid hormone concentrations, serum TSH, and thyroid gland growth in mice. Therefore, we tested the hypothesis that microsomal enzyme inducers induce T(4) UDP-GT activity, resulting in reduced serum T(4) concentrations, as well as increased serum TSH and thyroid follicular cell proliferation in mice. B6C3F male mice were fed a control diet or a diet containing PB (600, 1200, 1800, or 2400 ppm), PCN (250, 500, 1000, or 2000 ppm), 3MC (62.5, 125, 250, or 500 ppm), or PCB (10, 30, 100, or 300 ppm) for 21 days. All four inducers increased liver weight and hepatic microsomal UDP-GT activity toward chloramphenicol, alpha-naphthol, and T(4). PB and PCB decreased serum total T(4), but PCN and 3MC did not. Serum thyroid stimulating hormone was markedly increased by PCN and 3MC treatments, and slightly increased by PB and PCB treatments. All four microsomal enzyme inducers dramatically increased thyroid follicular cell proliferation in mice. The findings suggest that PB, PCN, 3MC, and PCB disrupt thyroid hormone homeostasis in mice.

  17. MODEST THYROID HORMONE INSUFFICIENCY DURING DEVELOPMENT INDUCES A CELLULAR MALFORMATION IN THE CORPUS CALLOSUM: A MODEL OF CORTICAL DYSPLASIA.

    EPA Science Inventory

    There is a growing body of evidence that subtle decreases in maternal thyroid hormone during gestation can impact fetal brain development. The present study examined the impact of graded levels of thyroid hormone insufficiency on brain development in rodents. Maternal thyroid ho...

  18. KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats.

    PubMed

    Helena, Cleyde V; Toporikova, Natalia; Kalil, Bruna; Stathopoulos, Andrea M; Pogrebna, Veronika V; Carolino, Ruither O; Anselmo-Franci, Janete A; Bertram, Richard

    2015-11-01

    Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges.

  19. Hormone Therapy

    MedlinePlus

    ... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  20. Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.

    PubMed

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Fu, Liezhen; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2016-11-21

    In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2016.

  1. Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis

    PubMed Central

    Fan, Yi; Bi, Ruiye; Densmore, Michael J.; Sato, Tadatoshi; Kobayashi, Tatsuya; Yuan, Quan; Zhou, Xuedong; Erben, Reinhold G.; Lanske, Beate

    2016-01-01

    Parathyroid-hormone–type 1 receptor (PTH1R) is extensively expressed in key regulatory organs for systemic mineral ion homeostasis, including kidney and bone. We investigated the bone-specific functions of PTH1R in modulating mineral ion homeostasis by generating a novel mouse model in which PTH1R is ablated in the limb mesenchyme using Prx1Cre transgenic mice. Such ablation decreased FGF23 protein and serum levels by 50%, despite normal Fgf23 mRNA levels in long bones. Circulating calcium and PTH levels were unchanged, but inorganic phosphate and 1,25(OH)2D3 levels were significantly decreased and accompanied by elevated urinary calcium and phosphate wasting. Key renal genes for balancing mineral ion homeostasis, calbindinD28k, Klotho, and Napi2a were suppressed by 30–40%. Intermittent hPTH(1–34) injections increased Fgf23 mRNA (7.3-fold), Nurr1 mRNA (3.1-fold), and serum intact-FGF23 (1.6-fold) in controls, but failed to induce Fgf23, Nurr1 mRNA, or intact FGF23 production in mutants. Moreover, a significant elevation in serum C-terminal-FGF23 levels (4-fold) was detected in both genotypes. PTH markedly downregulated Galnt3 expression (2.7-fold) in controls but not in mutants. These results demonstrate the pivotal role of PTH1R in long bones to regulate systemic mineral ion homeostasis and the direct induction of FGF23 by PTH1R signaling.—Fan, Y., Bi, R., Densmore, M. J., Sato, T., Kobayashi, T., Yuan, Q., Zhou, X., Erben, R. G., Lanske, B. Parathyroid hormone 1 receptor is essential to induce FGF23 production and maintain systemic mineral ion homeostasis. PMID:26428657

  2. Luteinizing Hormone-Induced RUNX1 Regulates the Expression of Genes in Granulosa Cells of Rat Periovulatory Follicles

    PubMed Central

    Jo, Misung; Curry, Thomas E.

    2006-01-01

    The LH surge induces specific transcription factors that regulate the expression of a myriad of genes in periovulatory follicles to bring about ovulation and luteinization. The present study determined 1) the localization of RUNX1, a nuclear transcription factor, 2) regulation of Runx1 mRNA expression, and 3) its potential function in rat ovaries. Up-regulation of mRNA and protein for RUNX1 is detected in preovulatory follicles after human chorionic gonadotropin (hCG) injection in gonadotropin-treated immature rats as well as after the LH surge in cycling animals by in situ hybridization and immunohistochemical and Western blot analyses. The regulation of Runx1 mRNA expression was investigated in vitro using granulosa cells from rat pre-ovulatory ovaries. Treatments with hCG, forskolin, or phorbol 12 myristate 13-acetate stimulated Runx1 mRNA expression. The effects of hCG were reduced by inhibitors of protein kinase A, MAPK kinase, or p38 kinase, indicating that Runx1 expression is regulated by the LH-initiated activation of these signaling mediators. In addition, hCG-induced Runx1 mRNA expression was inhibited by a progesterone receptor antagonist and an epidermal growth factor receptor tyrosine kinase inhibitor, whereas amphiregulin stimulated Runx1 mRNA expression, demonstrating that the expression is mediated by the activation of the progesterone receptor and epidermal growth factor receptor. Finally, knockdown of Runx1 mRNA by small interfering RNA decreased progesterone secretion and reduced levels of mRNA for Cyp11a1, Hapln1, Mt1a, and Rgc32. The hormonally regulated expression of Runx1 in periovulatory follicles, its involvement in progesterone production, and regulation of preovulatory gene expression suggest important roles of RUNX1 in the periovulatory process. PMID:16675540

  3. Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia.

    PubMed

    Oest, Megan E; Gong, Bo; Esmonde-White, Karen; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A; Morris, Michael D

    2016-05-01

    As part of our ongoing efforts to understand underlying mechanisms contributing to radiation-associated bone fragility and to identify possible treatments, we evaluated the longitudinal effects of parathyroid hormone (PTH) treatment on bone quality in a murine model of limited field irradiation. We hypothesized PTH would mitigate radiation-induced changes in the chemical composition and structure of bone, as measured by microscope-based Raman spectroscopy. We further hypothesized that collagen crosslinking would be especially responsive to PTH treatment. Raman spectroscopy was performed on retrieved tibiae (6-7/group/time point) to quantify metrics associated with bone quality, including: mineral-to-matrix ratio, carbonate-to-phosphate ratio, mineral crystallinity, collagen crosslink (trivalent:divalent) ratio, and the mineral and matrix depolarization ratios. Irradiation disrupted the molecular structure and orientation of bone collagen, as evidenced by a higher collagen crosslink ratio and lower matrix depolarization ratio (vs. non-irradiated control bones), persisting until 12weeks post-irradiation. Radiation transiently affected the mineral phase, as evidenced by increased mineral crystallinity and mineral-to-matrix ratio at 4weeks compared to controls. Radiation decreased bone mineral depolarization ratios through 12weeks, indicating increased mineral alignment. PTH treatment partially attenuated radiation-induced increases in collagen crosslink ratio, but did not restore collagen or mineral alignment. These post-radiation matrix changes are consistent with our previous studies of radiation damage to bone, and suggest that the initial radiation damage to bone matrix has extensive effects on the quality of tissue deposited thereafter. In addition to maintaining bone quality, preventing initial radiation damage to the bone matrix (i.e. crosslink ratio, matrix orientation) may be critical to preventing late-onset fragility fractures.

  4. Detecting the Hormonal Pathways in Oilseed Rape behind Induced Systemic Resistance by Trichoderma harzianum TH12 to Sclerotinia sclerotiorum

    PubMed Central

    Alkooranee, Jawadayn Talib; Aledan, Tamarah Raad; Ali, Ali Kadhim; Lu, Guangyuan; Zhang, Xuekun; Wu, Jiangsheng; Fu, Chunhua

    2017-01-01

    Plants have the ability to resist pathogen attack after infection or treatment with biotic and abiotic elicitors. In oilseed rape plant Brassica napus AACC and in the artificially synthesized Raphanus alboglabra RRCC, the root-colonizing Trichoderma harzianum TH12 fungus triggers induced systemic resistance (ISR), and its culture filtrate (CF) triggers a systemic acquired resistance (SAR) response against infection by the Sclerotinia sclerotiorum. Salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) are plant hormone signals that play important roles in the regulation of ISR and SAR. In this study, at six different time points (1, 2, 4, 6, 8 and 10 days post-infection [dpi]), six resistance genes were used as markers of signaling pathways: JA/ET signaling used AOC3, PDF1.2 and ERF2 genes, while PR-1, TGA5 and TGA6 genes were used as markers of SA signaling. The results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that AOC3, PDF1.2 and ERF2 expression levels in infected leaves of AACC and RRCC increase at 1 and 2 dpi with S. sclerotiorum or inoculation with TH12. PR-1, TGA5 and TGA6 expression levels increased at 8 and 10 dpi in infected leaves. PR-1, TGA5 and TGA6 expression levels increased early in plants treated with CF in both of the healthy genotypes. Furthermore, induction of SA- and JA/ET-dependent defense decreased disease symptoms in infected leaves at different times. The results suggest that the RRCC genotype exhibits resistance to disease and that the ability of TH12 and its CF to induce systemic resistance in susceptible and resistant oilseed rape genotypes exists. In addition, the results indicate for the first time that in RRCC the SA signaling pathway is involved in resistance to necrotrophic pathogens. PMID:28045929

  5. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers

    PubMed Central

    Váradi, Judit; Harazin, András; Fenyvesi, Ferenc; Réti-Nagy, Katalin; Gogolák, Péter; Vámosi, György; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Vasvári, Gábor; Róka, Eszter; Haines, David; Deli, Mária A.; Vecsernyés, Miklós

    2017-01-01

    Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB) was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines. PMID:28103316

  6. Detecting the Hormonal Pathways in Oilseed Rape behind Induced Systemic Resistance by Trichoderma harzianum TH12 to Sclerotinia sclerotiorum.

    PubMed

    Alkooranee, Jawadayn Talib; Aledan, Tamarah Raad; Ali, Ali Kadhim; Lu, Guangyuan; Zhang, Xuekun; Wu, Jiangsheng; Fu, Chunhua; Li, Maoteng

    2017-01-01

    Plants have the ability to resist pathogen attack after infection or treatment with biotic and abiotic elicitors. In oilseed rape plant Brassica napus AACC and in the artificially synthesized Raphanus alboglabra RRCC, the root-colonizing Trichoderma harzianum TH12 fungus triggers induced systemic resistance (ISR), and its culture filtrate (CF) triggers a systemic acquired resistance (SAR) response against infection by the Sclerotinia sclerotiorum. Salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) are plant hormone signals that play important roles in the regulation of ISR and SAR. In this study, at six different time points (1, 2, 4, 6, 8 and 10 days post-infection [dpi]), six resistance genes were used as markers of signaling pathways: JA/ET signaling used AOC3, PDF1.2 and ERF2 genes, while PR-1, TGA5 and TGA6 genes were used as markers of SA signaling. The results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that AOC3, PDF1.2 and ERF2 expression levels in infected leaves of AACC and RRCC increase at 1 and 2 dpi with S. sclerotiorum or inoculation with TH12. PR-1, TGA5 and TGA6 expression levels increased at 8 and 10 dpi in infected leaves. PR-1, TGA5 and TGA6 expression levels increased early in plants treated with CF in both of the healthy genotypes. Furthermore, induction of SA- and JA/ET-dependent defense decreased disease symptoms in infected leaves at different times. The results suggest that the RRCC genotype exhibits resistance to disease and that the ability of TH12 and its CF to induce systemic resistance in susceptible and resistant oilseed rape genotypes exists. In addition, the results indicate for the first time that in RRCC the SA signaling pathway is involved in resistance to necrotrophic pathogens.

  7. Protection from radiation-induced damage to spermatogenesis by hormone treatment

    SciTech Connect

    Kurdoglu, B.; Wilson, G.; Parchuri, N.; Ye, W.; Meistrich, M.L.

    1994-07-01

    Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs.

  8. Integrated physiological and hormonal profile of heat-induced thermotolerance in Pinus radiata.

    PubMed

    Escandón, Mónica; Cañal, María Jesús; Pascual, Jesús; Pinto, Glória; Correia, Barbara; Amaral, Joana; Meijón, Mónica

    2016-01-01

    Despite great interest, not only from the economic point of view but also in terms of basic science, research on heat stress tolerance in conifers remains scarce. To fill this gap, a time-course experiment using expected temperature increase was performed aiming to identify physiological and biochemical traits that allow the characterization of heat-induced thermotolerance and recovery in Pinus radiata D. Don plants. Several physiological parameters were assessed during heat exposure and after recovery, and multiple phytohormones-abscisic acid (ABA), indole-3-acetic acid (IAA), cytokinins (CKs), gibberellins, jasmonic acid, salicylic acid (SA) and brassinosteroids-were quantified by ultra-performance liquid chromatography-mass spectrometry from unique sample. Furthermore, tissue specific stress-signaling was monitored by IAA and ABA immunolocalization. Multivariate statistical analysis of the data enabled clustering of the shorter- and longer-term effects of heat stress exposure. Two sequential physiological responses were identified: an immediate and a delayed response, essentially determined by specific phytohormones, proline, malondialdehyde and total soluble sugar patterns. Results showed that ABA and SA play a crucial role in the first stage of response to heat stress, probably due to the plant's urgent need to regulate stomatal closure and counteract the increase in oxidative membrane damage demonstrated in shorter-term exposures. However, in longer exposures and recovery, proline, total sugars, IAA and CKs seem to be more relevant. This integrated approach pinpointed some basic mechanisms of P. radiata physiological responses underlying thermotolerance processes and after recovery.

  9. Bone and hormonal changes induced by skeletal unloading in the mature male rat

    NASA Technical Reports Server (NTRS)

    Dehority, W.; Halloran, B. P.; Bikle, D. D.; Curren, T.; Kostenuik, P. J.; Wronski, T. J.; Shen, Y.; Rabkin, B.; Bouraoui, A.; Morey-Holton, E.

    1999-01-01

    To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

  10. Parathyroid hormone induces c-fos and c-jun messenger RNA in rat osteoblastic cells

    NASA Technical Reports Server (NTRS)

    Clohisy, J. C.; Scott, D. K.; Brakenhoff, K. D.; Quinn, C. O.; Partridge, N. C.

    1992-01-01

    PTH is a potent regulator of osteoblast gene expression, yet the nuclear events that mediate PTH action are poorly understood. We were interested in identifying immediate early genes which may regulate PTH-altered gene expression in the osteoblast. Therefore, we examined the effects of PTH on c-fos and c-jun gene expression in a rat osteoblastic cell line (UMR 106-01). Under control conditions, c-fos and c-jun mRNAs were present at low basal levels. After PTH treatment, c-fos mRNA abundance dramatically increased, with a maximal and transient response at 30 min. PTH also stimulated an increase in c-jun mRNA, but in a biphasic manner, with maximal levels at 30 min and 2 h. These responses were dose dependent, not altered by cotreatment with the protein synthesis inhibitor cycloheximide, and preceded PTH-induced expression of matrix metallo-proteinase-1 mRNA. Nuclear run-on assays demonstrated an increased rate of c-fos and c-jun transcription after PTH exposure. To determine the signal transduction pathways involved, second messenger analogs were tested for their ability to mimic the effects of PTH. 8-Bromo-cAMP and phorbol 12-myristate 13-acetate (PMA) caused increases in the abundance of c-fos and c-jun transcripts. Ionomycin had no effect on the expression of these genes. Pretreatment of the cells with PMA resulted in a decrease in basal c-jun expression, but did not alter the PTH-mediated increase in c-fos, c-jun, or matrix metalloproteinase-1 mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS).

  11. Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced melanogenesis.

    PubMed

    Wen, Kuo-Ching; Chang, Chih-Shiang; Chien, Yin-Chih; Wang, Hsiao-Wen; Wu, Wan-Chen; Wu, Chin-Sheng; Chiang, Hsiu-Mei

    2013-11-28

    Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

  12. Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats.

    PubMed

    Bielohuby, Maximilian; Sawitzky, Mandy; Stoehr, Barbara J M; Stock, Peggy; Menhofer, Dominik; Ebensing, Sabine; Bjerre, Mette; Frystyk, Jan; Binder, Gerhard; Strasburger, Christian; Wu, Zida; Christ, Bruno; Hoeflich, Andreas; Bidlingmaier, Martin

    2011-05-01

    GH is a well established regulator of growth, lipid, and glucose metabolism and therefore important for fuel utilization. However, little is known about the effects of macronutrients on the GH/IGF system. We used low-carbohydrate/high-fat diets (LC-HFD) as a model to study the impact of fat, protein, and carbohydrates on the GH/IGF-axis; 12-wk-old Wistar rats were fed either regular chow, a moderate, protein-matched LC-HFD, or a ketogenic LC-HFD (percentage of fat/protein/carbohydrates: chow, 16.7/19/64.3; LC-HF-1, 78.7/19.1/2.2; LC-HF-2, 92.8/5.5/1.7). After 4 wk, body and tibia length, lean body mass, and fat pad weights were measured. Furthermore, we investigated the effects of LC-HFD on 1) secretion of GH and GH-dependent factors, 2) expression and signaling of components of the GH/IGF system in liver and muscle, and 3) hypothalamic and pituitary regulation of GH release. Serum concentrations of IGF-I, IGF binding protein-1, and IGF binding protein-3 were lower with LC-HF-1 and LC-HF-2 (P < 0.01). Both LC-HFD-reduced hepatic GH receptor mRNA and protein expression, decreased basal levels of total and phosphorylated Janus kinase/signal transducers and activators of transcription signaling proteins and reduced hepatic IGF-I gene expression. Hypothalamic somatostatin expression was reduced only with LC-HF-1, leading to increased pituitary GH secretion, higher IGF-I gene expression, and activation of IGF-dependent signaling pathways in skeletal muscle. In contrast, despite severely reduced IGF-I concentrations, GH secretion did not increase with LC-HF-2 diet. In conclusion, lack of carbohydrates in LC-HFD induces hepatic GH resistance. Furthermore, central feedback mechanisms of the GH/IGF system are impaired with extreme, ketogenic LC-HFD.

  13. Hormone-induced increase in free cytosolic calcium and glycogen phosphorylase activation in rat hepatocytes incubated in normal and low-calcium media.

    PubMed Central

    Binet, A; Berthon, B; Claret, M

    1985-01-01

    The action of alpha 1-adrenergic agonists (noradrenaline in the presence of propranolol), vasopressin and angiotensin on the intracellular free Ca2+ concentration, [Ca2+]i, was determined by using the fluorescent dye quin2 in isolated rat liver cells. In the presence of external Ca2+ (1.8 mM), 1 microM-noradrenaline induced an increase in [Ca2+]i up to about 800 nM without apparent delay, whereas 10 nM-vasopressin and 1 nM-angiotensin increased [Ca2+]i to values higher than 1500 nM with a lag period of about 6s. The successive addition of the hormones and of their specific antagonists indicated that the actions of the three Ca2+-mobilizing hormones occurred without apparent desensitization (over 6 min) and via independent receptors. The relative contributions of internal and external Ca2+ pools to the cell response were determined by studying the hormone-mediated [Ca2+]i increase and glycogen phosphorylase activation in low-Ca2+ media (22 microM). In this medium: (1) [Ca2+]i was lowered and the hormones initiated a transient instead of a sustained increase in [Ca2+]i; subsequent addition (2 min) of a second hormone promoted a lesser increase in [Ca2+]i; in contrast, the subsequent addition (2 min) of Ca2+ (1.8 mM) caused [Ca2+]i to increase to a value close to that initiated by the hormone in control conditions, the amplitude of the latter response being dependent on the concentration of Ca2+ added to the medium; (2) returning to normal Ca2+ (1.8 mM) restored the resting [Ca2+]i and allowed the hormone added 2 min later to promote a large increase in [Ca2+]i whose final amplitude was also dependent on the concentration of Ca2+ added beforehand. Similar results were found when the same protocol was applied to the glycogen phosphorylase activation. It is concluded that Ca2+ influx is required for a maximal and sustained response and to reload the hormone-sensitive stores. PMID:4026798

  14. Subsets of gonadotropin-releasing hormone (GnRH) neurons are activated during a steroid-induced luteinizing hormone surge and mating in mice: a combined retrograde tracing double immunohistochemical study.

    PubMed

    Rajendren, G

    2001-11-09

    The decapeptide gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproduction and is synthesized by GnRH-producing cell bodies in the basal forebrain. Experiments were designed to investigate whether GnRH cells projecting outside the blood brain barrier or those projecting within the brain are activated during the steroid-induced LH surge or mating in female mice. Retrograde uptake of intraperitoneally administered fluorogold (FG) by GnRH cells and double immunostaining for GnRH and Fos was employed for this purpose. The number of GnRH cells with FG uptake was comparable among the surged, mated and control mice. However, the number of Fos-positive GnRH cells was significantly higher in the steroid-induced LH surge group than in the mated mice. The number of Fos+FG-positive GnRH cells was higher and the number of FG-only GnRH cells was lower in mice with a steroid-induced LH surge as compared with the mated mice. This suggests the existence of a subgroup of GnRH cells projecting outside the blood-brain barrier activated during the steroid-induced LH surge but not during mating. The activation of similar proportions of GnRH cells without FG uptake in both the mated and the surge group indicate that nonneuroendocrine GnRH cells are not silent but can be activated by both mating and steroid hormones. Thus, functional subgroups may exist within the GnRH system with considerable overlap in the input to these cells.

  15. Protein kinase C is necessary for recovery from the thyrotropin-releasing hormone-induced r-ERG current reduction in GH3 rat anterior pituitary cells

    PubMed Central

    Gómez-Varela, David; Giráldez, Teresa; la Peña, Pilar de; Dupuy, Silvia G; García-Manso, Diego; Barros, Francisco

    2003-01-01

    The biochemical cascade linking activation of phospholipase C-coupled thyrotropin-releasing hormone (TRH) receptors to rat ERG (r-ERG) channel modulation was studied in situ using perforated-patch clamped adenohypophysial GH3 cells and pharmacological inhibitors. To check the recent suggestion that Rho kinase is involved in the TRH-induced r-ERG current suppression, the hormonal effects were studied in cells pretreated with the Rho kinase inhibitors Y-27632 and HA-1077. The TRH-induced r-ERG inhibition was not significantly modified in the presence of the inhibitors. Surprisingly, the hormonal effects became irreversible in the presence of HA-1077 but not in the presence of the more potent Rho kinase inhibitor Y-27632. Further experiments indicated that the effect of HA-1077 correlated with its ability to inhibit protein kinase C (PKC). The hormonal effects also became irreversible in cells in which PKC activity was selectively impaired with GF109203X, Gö6976 or long-term incubation with phorbol esters. Furthermore, the reversal of the effects of TRH, but not its ability to suppress r-ERG currents, was blocked if diacylglycerol generation was prevented by blocking phospholipase C activity with U-73122. Our results suggest that a pathway involving an as yet unidentified protein kinase is the main cause of r-ERG inhibition in perforated-patch clamped GH3 cells. Furthermore, they demonstrate that although not necessary to trigger the ERG current reductions induced by TRH, an intracellular signal cascade involving phosphatidylinositol-4,5-bisphosphate hydrolysis by phospholipase C, activation of an α/βII conventional PKC and one or more dephosphorylation steps catalysed by protein phosphatase 2A, mediates recovery of ERG currents following TRH withdrawal. PMID:12562894

  16. Structural Abnormalities and Learning Impairments Induced by Low Level Thyroid Hormone Insufficiency: A Cross-Fostering Study

    EPA Science Inventory

    Severe reductions in thyroid hormones (TH) during development alter brain structure and impair learning. Uncertainty surrounds both the impact oflower levels of TH disruption and the sensitivity of available metrics to detect neurodevelopmental deficits of this disruption. We ha...

  17. INTERACTION BETWEEN GABA AND NOREPINEPHRINE IN INTERLEUKIN-1β-INDUCED SUPPRESSION OF THE LUTEINIZING HORMONE SURGE

    PubMed Central

    Sirivelu, Madhu P.; Burnett, Robert; Shin, Andrew C.; Kim, Charlotte; MohanKumar, P.S.; MohanKumar, Sheba M.J.

    2009-01-01

    Interleukin-1β (IL-1β), a cytokine that is closely associated with inflammation and immune stress, is known to interfere with reproductive functions. Earlier studies have demonstrated that IL-1β inhibits the luteinizing hormone (LH) surge during the afternoon of proestrus in female rats. We have shown that this effect is most probably mediated through a reduction in norepinephrine (NE) levels in the medial preoptic area (MPA) of the hypothalamus. However, the mechanism by which IL-1β decreases NE levels in the MPA is unclear. We hypothesized that the inhibitory neurotransmitter, GABA could play a role in decreasing NE levels in the MPA. To test this, ovariectomized, steroid-primed rats were injected (i.p.) with either PBS-BSA (control) or 5 μg of IL-1β, alone or in combination with i.c.v. administration of GABA-A and GABA-B receptor antagonists, Bicuculline and CGP 35348 (CGP) respectively. Animals were subjected to push-pull perfusion of the MPA and perfusates collected at 30 min intervals were analyzed for both NE and GABA levels using HPLC-EC. Simultaneously, serial plasma samples were obtained through jugular catheters and were analyzed for LH levels using RIA. Compared to control rats, NE levels decreased significantly in the MPA in IL-1β-treated rats (p<0.05). Concurrently, there was a significant increase in GABA levels in the MPA (p<0.05). The GABA-A receptor antagonist, bicuculline, was able to reverse the effect of IL-1β on NE and LH, while the GABA-B receptor antagonist, CGP 35348 was without any effect. This leads us to conclude that the IL-1β-induced suppression of the LH surge is most probably mediated through an increase in GABA levels in the MPA which causes a reduction in NE levels. This is probably one of the mechanisms by which IL-1β inhibits reproductive functions. PMID:19014915

  18. Foliar application of methyl jasmonate induced physio-hormonal changes in Pisum sativum under diverse temperature regimes.

    PubMed

    Shahzad, Raheem; Waqas, Muhammad; Khan, Abdul Latif; Hamayun, Muhammad; Kang, Sang-Mo; Lee, In-Jung

    2015-11-01

    Global climate change brings with it unwarranted shifts in both abiotic (heat stress, cold stress, wind, precipitation) and biotic (pathogens, pests) environmental factors, thus posing a threat to agricultural productivity across the world. In plants, lodging due to storms or herbivory causes wounding stress and consequently enhances endogenous jasmonates. In response, the plant growth is arrested as plant defense is prioritized. We pre-treated pea plants with elevated methyl jasmonate (MeJA) levels i.e. 50 μM, 100 μM and 200 μM under controlled growth chamber conditions. The pre-treated plants were then kept at 40 °C (heat stress--HS), 4 °C (cold stress--CS) and 20 °C (optimum/control temperature--OT) for 72 h. The effect of such treatments on plant growth attributes, photosynthesis, stomatal conductance, cell death rate, and regulation of endogenous hormones were observed. Elevated MeJA application hindered plant growth attributes under HS, CS and OT conditions. Moreover, elevated MeJA levels lowered the rate of photosynthesis and stomatal conductance, induced stomatal closure, caused higher cells mortality in leaves under HS, CS, and OT conditions. Endogenous ABA contents significantly declined in all MeJA treatments under HS and OT, but increased under CS conditions. Exogenous MeJA enhanced endogenous jasmonic acid contents of pea plants, but altered endogenous salicylic acid contents under varying temperatures. Current study shows that higher concentrations of exogenous MeJA strengthen plant defense mechanism by hindering plant growth under stress conditions.

  19. Hormone crosstalk in wound stress response: wound-inducible amidohydrolases can simultaneously regulate jasmonate and auxin homeostasis in Arabidopsis thaliana

    PubMed Central

    Zhang, Tong; Poudel, Arati N.; Jewell, Jeremy B.; Kitaoka, Naoki; Staswick, Paul; Matsuura, Hideyuki; Koo, Abraham J.

    2016-01-01

    Jasmonate (JA) and auxin are essential hormones in plant development and stress responses. While the two govern distinct physiological processes, their signaling pathways interact at various levels. Recently, members of the Arabidopsis indole-3-acetic acid (IAA) amidohydrolase (IAH) family were reported to metabolize jasmonoyl-isoleucine (JA-Ile), a bioactive form of JA. Here, we characterized three IAH members, ILR1, ILL6, and IAR3, for their function in JA and IAA metabolism and signaling. Expression of all three genes in leaves was up-regulated by wounding or JA, but not by IAA. Purified recombinant proteins showed overlapping but distinct substrate specificities for diverse amino acid conjugates of JA and IAA. Perturbed patterns of the endogenous JA profile in plants overexpressing or knocked-out for the three genes were consistent with ILL6 and IAR3, but not ILR1, being the JA amidohydrolases. Increased turnover of JA-Ile in the ILL6- and IAR3-overexpressing plants created symptoms of JA deficiency whereas increased free IAA by overexpression of ILR1 and IAR3 made plants hypersensitive to exogenous IAA conjugates. Surprisingly, ILL6 overexpression rendered plants highly resistant to exogenous IAA conjugates, indicating its interference with IAA conjugate hydrolysis. Fluorescent protein-tagged IAR3 and ILL6 co-localized with the endoplasmic reticulum-localized JA-Ile 12-hydroxylase, CYP94B3. Together, these results demonstrate that in wounded leaves JA-inducible amidohydrolases contribute to regulate active IAA and JA-Ile levels, promoting auxin signaling while attenuating JA signaling. This mechanism represents an example of a metabolic-level crosstalk between the auxin and JA signaling pathways. PMID:26672615

  20. Parathyroid Hormone-Induced Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and its Repair of Articular Cartilage Injury in Rabbits

    PubMed Central

    Chen, Yushu; Chen, Yi; Zhang, Shujiang; Du, Xiufan; Bai, Bo

    2016-01-01

    Background We explored the effect of parathyroid hormone (PTH)-induced bone marrow stem cells (BMSCs) complexed with fibrin glue (FG) in the repair of articular cartilage injury in rabbits. Material/Methods Forty-eight rabbits randomized into four groups were subjected to articular surgery (cartilage loss). The PTH and non-PTH intervention groups included transplantation with PTH/BMSC/FG xenogeneic and BMSC/FG xenogeneic complexes, respectively, into the injured area. The injured group contained no transplant while the control group comprised rabbits without any articular injury. Samples were monitored for cartilage repair up to three months post-surgery. Immunohistochemistry as well as real-time fluorescent quantitative PCR and Western blot were used to analyze the expression of type II collagen and aggrecan in the repaired tissue. Results At 12 weeks post-surgery, the loss of articular cartilage in the PTH group was fully repaired by hyaline tissue. Typical cartilage lacunae and intact subchondral bone were found. The boundary separating the surrounding normal cartilage tissue disappeared. The gross and International Cartilage Repair Society (ICRS) histological ranking of the repaired tissue was significantly higher in the PTH intervention group than in the non-PTH intervention and injury groups (p<0.05) without any significant difference compared to the control group (p>0.05). Type II collagen and aggrecan stained positive and the average optical density, relative mRNA expression and protein-integrated optical density in the PTH group were higher than in non-PTH and injured groups (p<0.05) but not significantly different from the control group (p>0.05). Conclusions PTH/BMSC/FG xenogeneic complexes effectively repaired the loss of cartilage in rabbit knee injury. PMID:27847384

  1. The effects of palm vitamin E on stress hormone levels and gastric lesions in stress-induced rats

    PubMed Central

    Aziz Ibrahim, Ibrahim Abdel; Kamisah, Yusof; Nafeeza, Mohd Ismail

    2012-01-01

    Introduction This study examines the effects of palm vitamin E (PVE) or α-tocopherol (α-TF) supplementation on adrenocorticotropin hormone (ACTH), corticosterone and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Material and methods Sixty male Sprague-Dawley rats (200-250 g) were divided into three groups. Group I: 20 rats as a control group were given a normal diet. Group II: 20 rats received oral supplementation of PVE at 60 mg/kg body weight. Group III: 20 rats received oral supplementation of α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups: 10 rats not exposed to stress, and the other 10 rats subjected to WIRS for 3.5 h. Blood samples were taken to measure the ACTH and corticosterone levels. The rats were then sacrificed and the stomach excised and opened along the greater curvature and examined for lesions. Results Rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementation of PVE or α-TF was able to reduce gastric lesions significantly in comparison to the stressed controls. The WIRS increased plasma ACTH and corticosterone significantly. Palm vitamin E and α-TF treatments reduced these parameters significantly compared to the stressed controls. Conclusions Supplementation with either PVE or α-TF reduces the formation of gastric lesions, probably by inhibiting the elevation of ACTH and corticosterone levels induced by stress. PMID:22457670

  2. Anti-mullerian hormone is expressed by endometriosis tissues and induces cell cycle arrest and apoptosis in endometriosis cells

    PubMed Central

    2014-01-01

    Background The anti-mullerian hormone (AMH) is a member of the transforming growth factor β (TGF-β) superfamily, which is responsible of the regression of the mullerian duct. AMH is expressed in the normal endometrium, where, acting in a paracrine fashion, negatively regulates cellular viability. Our objective was to evaluate the in vitro effects of the treatment with AMH of endometriosic cells. Methods AMH expression in human endometriosis glands was evaluated by immunohistochemistry. RT-PCR has been used to quantify the expression levels of AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity. Results AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in both endometriosis epithelial and stromal cells. Treatment of endometriosis stromal and epithelial cell growth with AMH was able to induce a decrease in the percentage of cells in S phase and increase percentage of cells in G1 and G2 phase; coherently, decreased cell viability and increased percentage of cells death fraction was observed. The plasmin-digested AMH was able to suppress most of the cytochrome P450 activity, causing an increase of pre-G1 phase and of apoptosis induction treating with plasmin-digested AMH in both cell lines, most marked in the epithelial cells. Conclusions The data produced suggest a possible use of AMH as therapeutic agents in endometriosis. PMID:24886254

  3. Functional significance of parasitism-induced suppression of juvenile hormone esterase activity in developmentally delayed Choristoneura fumiferana larvae.

    PubMed

    Cusson, M; Laforge, M; Miller, D; Cloutier, C; Stoltz, D

    2000-03-01

    The parasitic wasp Tranosema rostrale transmits a polydnavirus (PDV) to its host, Choristoneura fumiferana, during oviposition. Last-instar C. fumiferana larvae parasitized by T. rostrale early in the stadium fail to undergo metamorphosis, and injection of the wasp's calyx fluid (CxF; contains PDV) into healthy caterpillars induces a dose-dependent delay in initiation of metamorphosis (D. Doucet and M. Cusson, 1996, Entomol. Exp. Appl. 81, 21-30). In the present work, parasitization and injection of CxF (0.5 female equivalent) on the first day of the last stadium both prevented the rise in hemolymph 20-hydroxyecdysone (20HE) titer observed between day 4 and day 7 in control and saline-injected larvae. Similarly, juvenile hormone esterase (JHE) activity was depressed following parasitization or CxF injection, whereas control larvae displayed a peak on day 4. However, neither parasitism nor injection of CxF on day 1 prevented the JH-producing glands from turning off during the first half of the last stadium. Likewise, low but clearly detectable JH titers were observed in the first hours following the molt but very low titers, at or near the detection limit of our radioimmunoassay, were seen in both control and parasitized larvae on day 4. Prothoracic glands showed no apparent sign of degeneration 4 days after injection of CxF but had significantly smaller cells than saline-injected larvae 7 days postinjection. It is not clear whether this was a direct effect of T. rostrale PDV. Thus, disruption of spruce budworm metamorphosis by T. rostrale CxF involves depression of 20HE titers but is not associated with a measurable increase in the level of JH, as shown for some other host-parasitoid systems. In view of the latter observation, we put forward three hypotheses regarding the functional significance of the observed suppression of JHE activity in developmentally arrested C. fumiferana larvae.

  4. Progesterone Receptor and Prostaglandins Mediate Luteinizing Hormone-Induced Changes in Messenger RNAs for ADAMTS Proteases in Theca Cells of Bovine Periovulatory Follicles

    PubMed Central

    WILLIS, ERIN L.; BRIDGES, PHILLIP J.; FORTUNE, JOANNE E.

    2017-01-01

    SUMMARY Little is known about the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of extracellular proteases in ovarian follicles of non-rodent species, particularly in theca cells. In the present study, temporal changes in the abundance of mRNA encoding four ADAMTS subtypes and hormonal regulation of mRNA encoding two subtypes were investigated in theca interna cells during the periovulatory period in cattle. Gonadotropin-releasing hormone (GnRH) was injected into animals to induce a luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge, and follicles were obtained at 0 hr post-GnRH (preovulatory) or at 6, 12, 18, or 24 hr (periovulatory). ADAMTS1, -2, -7, and -9 transcript abundance was then determined in the isolated theca interna. ADAMTS1 and -9 mRNA levels were up-regulated at 24 hr post-GnRH, whereas ADAMTS2 mRNA was higher at r12–24 hr post-GnRH and ADAMTS7 mRNA increased transiently at 12 hr post-GnRH compared to other time points. Subsequent in vitro experiments using preovulatory theca interna (0 hr post-GnRH) showed that application of LH in vitro can mimic the effects of the gonadotropin surge on mRNAs encoding ADAMTS1 and -9 and that progesterone/progesterone receptor and/or prostaglandins may regulate the levels of mRNA encoding ADAMTS1 and -9 in theca interna, downstream of the LH surge. Time- and subtype-specific changes in ADAMTS mRNA abundance in vivo, and their regulation in vitro by hormones, indicate that ADAMTS family members produced by theca cells may play important roles in follicle rupture and the accompanying tissue remodeling in cattle. PMID:27879029

  5. Farnesol induces thyroid hormone receptor (THR) {beta}1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells

    SciTech Connect

    Duncan, Robin E.; Archer, Michael C. . E-mail: m.archer@utoronto.ca

    2006-04-28

    Anti-cancer effects of farnesol are well established, although mechanisms mediating these effects are not fully understood. Since farnesol has been shown to regulate gene transcription through activation of the farnesoid X receptor and the peroxisome proliferator-activated receptors-{alpha} and -{gamma}, we hypothesized that farnesol may also mediate some of its effects through other nuclear hormone receptors. Here we showed that in MCF-7 human breast cancer cells, farnesol induced the expression of thyroid hormone receptor (THR) {beta}1 mRNA and protein at concentrations that inhibited cell growth. Changes in the expression of THR responsive genes, however, suggested that farnesol inhibits THR-mediated signaling. Protein extracts from cells treated with farnesol displayed decreased binding to oligodeoxynucleotides containing a consensus sequence for the THR response element, despite the higher THR{beta}1 content, providing a mechanism to explain the decreased transcriptional activity of cellular THRs.

  6. Epidermal growth factor receptor (EGFR) signaling is a key mediator of hormone-induced leukocyte infiltration in the pubertal female mammary gland.

    PubMed

    Aupperlee, Mark D; Zhao, Yong; Tan, Ying Siow; Leipprandt, Jeffrey R; Bennett, Jessica; Haslam, Sandra Z; Schwartz, Richard C

    2014-06-01

    It is well documented that macrophages and eosinophils play important roles in normal murine pubertal mammary gland development. Although it is accepted that estrogen (E) and progesterone (P) are key players in mammary gland development, the roles these hormones might play in regulating the actions of leukocytes in that process is an understudied area. We show here that P and E, respectively, induce unique, but overlapping, sets of proinflammatory and angiogenic cytokines and chemokines, in the pubertal female BALB/c mammary gland, as well as induce infiltration of macrophages and eosinophils to the mammary periepithelium. This extends earlier studies showing P induction of proinflammatory products in pubertal and adult mammary epithelial organoids and P-induced in vivo infiltration of leukocytes to the adult mammary periepithelium. Importantly, epidermal growth factor receptor-signaling, which is likely mediated by amphiregulin (Areg), a downstream mediator of E and P, is both necessary and sufficient for both E- and P-induced recruitment of macrophages and eosinophils to the pubertal mammary periepithelium. We further show that receptor activator of nuclear factor κB ligand (RANKL), although not sufficient of itself to cause macrophage and eosinophil recruitment, contributes to an optimal response to P. The potency of Areg is highlighted by the fact that it is sufficient to induce macrophage and eosinophil recruitment at levels equivalent to that induced by either E or P. Our finding of a dominant role for Areg in hormonally induced leukocyte recruitment to the pubertal mammary gland parallels its dominance in regulating ductal outgrowth and its role in P-induced proliferation in the pubertal gland.

  7. After-ripening induced transcriptional changes of hormonal genes in wheat seeds: the cases of brassinosteroids, ethylene, cytokinin and salicylic acid.

    PubMed

    Chitnis, Vijaya R; Gao, Feng; Yao, Zhen; Jordan, Mark C; Park, Seokhoon; Ayele, Belay T

    2014-01-01

    Maintenance and release of seed dormancy is regulated by plant hormones; their levels and seed sensitivity being the critical factors. This study reports transcriptional regulation of brassinosteroids (BR), ethylene (ET), cytokinin (CK) and salicylic acid (SA) related wheat genes by after-ripening, a period of dry storage that decays dormancy. Changes in the expression of hormonal genes due to seed after-ripening did not occur in the anhydrobiotic state but rather in the hydrated state. After-ripening induced dormancy decay appears to be associated with imbibition mediated increase in the synthesis and signalling of BR, via transcriptional activation of de-etiolated2, dwarf4 and brassinosteroid signaling kinase, and repression of brassinosteroid insensitive 2. Our analysis is also suggestive of the significance of increased ET production, as reflected by enhanced transcription of 1-aminocyclopropane-1-carboxylic acid oxidase in after-ripened seeds, and tight regulation of seed response to ET in regulating dormancy decay. Differential transcriptions of lonely guy, zeatin O-glucosyltransferases and cytokinin oxidases, and pseudo-response regulator between dormant and after-ripened seeds implicate CK in the regulation of seed dormancy in wheat. Our analysis also reflects the association of dormancy decay in wheat with seed SA level and NPR independent SA signaling that appear to be regulated transcriptionally by phenylalanine ammonia lyase, and whirly and suppressor of npr1 inducible1 genes, respectively. Co-expression clustering of the hormonal genes implies the significance of synergistic and antagonistic interaction between the different plant hormones in regulating wheat seed dormancy. These results contribute to further our understanding of the molecular features controlling seed dormancy in wheat.

  8. Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

    PubMed Central

    Zhang, Lei; Gong, Ji T; Zhang, Hu Q; Song, Quan H; Xu, Guang H; Cai, Lei; Tang, Xiao D; Zhang, Hai F; Liu, Fang-E; Jia, Zhan S; Zhang, Hong W

    2015-01-01

    Background/Aims There are increasing evidences for gastrointestinal motility disorder (GIMD) and gastric stress ulcer induced by noise stress. The present study was to investigate the reversed effect of melatonin on GIMD and gastric stress ulcer induced by noise stress and potential mechanism. Methods Noise stress was induced on rats, and melatonin (15 mg/kg) was administered to rats by intraperitoneal injection. Differences were assessed in gastric residual rate (GRR), small intestine propulsion rate (SPR), Guth injury score, cortisol, gastrointestinal hormones (calcitonin-gene-related peptide and motilin) and oxidative stress markers (superoxide dismutase and malondialde hyde) in blood plasma as well as gastric mucosa homogenate with or without melatonin. The pathological examination of gastric mucosa was also performed. Results The GRR and SPR were improved by noise stress compared with control (P < 0.05). The pathological examination and Guth injury score revealed gastric stress ulcer. Moreover, the levels of cortisol, motilin and malondialdehyde in blood plasma and malondialdehyde in gastric mucosa homogenate were increased by noise stress (P < 0.05). CGRP and superoxide dismutase activity in both of blood plasma and gastric mucosa homogenate were significantly decreased (P< 0.05). Furthermore, melatonin reversed changes in GRR, SPR, pathological examination, Guth injury score, cortisol, motilin, CGRP, superoxide dismutase activity and malondialdehyde (P < 0.05). Conclusions Melatonin is effective in reversing the GIMD and gastric stress ulcer induced by noise stress. The underlying mechanism may be involved in oxidative stress and gastrointestinal hormones. PMID:25537679

  9. Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

    PubMed

    Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Bartho, Julia; Blois, Sandra M; Karpf, Eva F; Sedlmayr, Peter; Klapp, Burghard F; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C

    2010-03-01

    Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH

  10. Parathyroid hormone induces epithelial-to-mesenchymal transition via the Wnt/β-catenin signaling pathway in human renal proximal tubular cells.

    PubMed

    Guo, Yunshan; Li, Zhen; Ding, Raohai; Li, Hongdong; Zhang, Lei; Yuan, Weijie; Wang, Yanxia

    2014-01-01

    Epithelial-to-mesenchymal transition (EMT) has been shown to play an important role in renal fibrogenesis. Recent studies suggested parathyroid hormone (PTH) could accelerate EMT and subsequent organ fibrosis. However, the precise molecular mechanisms underlying PTH-induced EMT remain unknown. The present study was to investigate whether Wnt/β-catenin signaling pathway is involved in PTH-induced EMT in human renal proximal tubular cells (HK-2 cells) and to determine the profile of gene expression associated with PTH-induced EMT. PTH could induce morphological changes and gene expression characteristic of EMT in cultured HK-2 cells. Suppressing β-catenin expression or DKK1 limited gene expression characteristic of PTH-induced EMT. Based on the PCR array analysis, PTH treatment resulted in the up-regulation of 18 genes and down-regulation of 9 genes compared with the control. The results were further supported by a western blot analysis, which showed the increased Wnt4 protein expression. Wnt4 overexpression also promotes PTH-induced EMT in HK-2 cells. The findings demonstrated that PTH-induced EMT in HK-2 cells is mediated by Wnt/β-catenin signal pathway, and Wnt4 might be a key gene during PTH-induced EMT.

  11. Feedback effects of estradiol and progesterone on ovulation and fertility of dairy cows after gonadotropin-releasing hormone-induced release of luteinizing hormone.

    PubMed

    Stevenson, J S; Pulley, S L

    2016-04-01

    An experiment was conducted with the objective to determine the effects of estradiol, progesterone, presence of a corpus luteum (CL), and size of a dominant follicle on the characteristics and patterns of GnRH-induced LH release and subsequent ovulation during a timed artificial insemination (TAI) program, or a combination of these. In 70 lactating dairy cows, a total of 163 blood collection periods resulting in a GnRH-induced LH release were analyzed. Concentrations of LH were measured in hourly samples (0 through 6 h after GnRH) during each of the blood collection periods, whereas concentrations of progesterone and estradiol were measured in the sample before GnRH treatment (0 h). Measures of LH included time to LH peak concentration during the 6-h blood collection period, the 2 largest concentrations of LH, mean, and variance of the 6 LH concentrations under each LH curve. Individual and combination effects of CL presence and a dominant follicle ≤ or >13.5mm, in addition to individual and combination effects of progesterone: low (<0.45 ng/mL; n=83), medium (0.53 to 2.41 ng/mL; n=25), and high (2.66 to 10.7 ng/mL; n=55), and estradiol: low (<4.0 pg/mL; n=89) and high (≥4.0 pg/mL; n=74) were independent variables in models to determine their influence on characteristics of LH and ovulation. Injections of GnRH induced LH release during 6 h after each of 163 injections. Measures of GnRH-induced LH concentration were inhibited at greater concentrations of progesterone and in the presence of a CL. In contrast, GnRH-induced LH concentrations were increased when estradiol was ≥4.0 pg/mL, but relatively unaffected by the size of the dominant follicle. Furthermore, resulting incidences of ovulation were decreased at greater progesterone concentrations and presence of a CL, and increased at greater estradiol concentrations and presence of follicles >13.5mm. In cows with or without a CL, the presence of a follicle >13.5mm did not increase mean LH concentration or

  12. Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

    PubMed

    Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

    2014-01-01

    We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

  13. Hormonal changes and increased anxiety-like behavior in a perimenopause-animal model induced by 4-vinylcyclohexene diepoxide (VCD) in female rats.

    PubMed

    Reis, F M C V; Pestana-Oliveira, N; Leite, C M; Lima, F B; Brandão, M L; Graeff, F G; Del-Ben, C M; Anselmo-Franci, J A

    2014-11-01

    Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.

  14. Developmental and hormone-induced changes of mitochondrial electron transport chain enzyme activities during the last instar larval development of maize stem borer, Chilo partellus (Lepidoptera: Crambidae).

    PubMed

    VenkatRao, V; Chaitanya, R K; Naresh Kumar, D; Bramhaiah, M; Dutta-Gupta, A

    2016-12-01

    The energy demand for structural remodelling in holometabolous insects is met by cellular mitochondria. Developmental and hormone-induced changes in the mitochondrial respiratory activity during insect metamorphosis are not well documented. The present study investigates activities of enzymes of mitochondrial electron transport chain (ETC) namely, NADH:ubiquinone oxidoreductase or complex I, Succinate: ubiquinone oxidoreductase or complex II, Ubiquinol:ferricytochrome c oxidoreductase or complex III, cytochrome c oxidase or complex IV and F1F0ATPase (ATPase), during Chilo partellus development. Further, the effect of juvenile hormone (JH) analog, methoprene, and brain and corpora-allata-corpora-cardiaca (CC-CA) homogenates that represent neurohormones, on the ETC enzyme activities was monitored. The enzymatic activities increased from penultimate to last larval stage and thereafter declined during pupal development with an exception of ATPase which showed high enzyme activity during last larval and pupal stages compared to the penultimate stage. JH analog, methoprene differentially modulated ETC enzyme activities. It stimulated complex I and IV enzyme activities, but did not alter the activities of complex II, III and ATPase. On the other hand, brain homogenate declined the ATPase activity while the injected CC-CA homogenate stimulated complex I and IV enzyme activities. Cumulatively, the present study is the first to show that mitochondrial ETC enzyme system is under hormone control, particularly of JH and neurohormones during insect development.

  15. Neutralizing circulating ghrelin by expressing a growth hormone secretagogue receptor-based protein protects against high-fat diet-induced obesity in mice.

    PubMed

    Gagnon, J; Zhu, L; Anini, Y; Wang, Q

    2015-09-01

    Ghrelin is a stomach-derived peptide hormone that stimulates appetite and promotes adiposity through binding to the growth hormone secretagogue receptor (GHS-R1a). Administration of ghrelin in rodents increases weight gain due to stimulating food intake and reducing fat utilization. Therefore, reducing circulating ghrelin levels holds the potential to reduce weight gain. We developed a GHS-R1a-fusion constructs of a decoy protein containing the ligand-binding domains of the ghrelin receptor. Intramuscular injection of the GHSR/Fc plasmid decreased circulating levels of acylated-ghrelin. When challenged with the high fat diet, treated mice displayed reduced weight gain compared with controls, which was associated with reduced fat accumulation in the peritoneum but not lean mass. Quantitative PCR with reverse transcription showed increased PPARγ and hormone sensitive lipase transcripts levels in adipose tissue of treated animals, illustrating a preference for increased fat utilization. Intra-peritoneal glucose tolerance and insulin tolerance tests showed improved glucose clearance and insulin sensitivity in GHSR/Fc treated animals. We suggest that in vivo expression of the GHSR-based fusion protein prevents diet-induced weight gain, altering adipose gene expression and improving glucose tolerance. These findings, while confirming the role of ghrelin in peripheral energy metabolism, suggest that a strategy involving neutralization of the circulation ghrelin by intramuscular injection of the GHSR1/Fc fusion construct may find clinical application in the treatment of obesity.

  16. CHANGES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS INDUCED IN MALE OFFSPRING AFTER MATERNAL TREATMENT WITH PHTHALATE ESTERS

    EPA Science Inventory

    Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice results in altered gubernacular development, disrupted testis decent, and cryptorchidism. Cryptorchidism is a fairly common human malformation, being displayed in 1-3% of males at birth. Since only a s...

  17. MODE OF ACTION: NEUROTOXICITY INDUCED BY DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY -- NEUROLOGICAL ABNORMALITIES RESULTING FROM EXPOSURE TO PROPYLTHIOURACIL.

    EPA Science Inventory

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. This specific report used animal data on neurodevelopmental effects of thyroid hormone disruption to test the framework. Polyhaloge...

  18. Hormone induces binding of receptors and transcription factors to a rearranged nucleosome on the MMTV promoter in vivo.

    PubMed Central

    Truss, M; Bartsch, J; Schelbert, A; Haché, R J; Beato, M

    1995-01-01

    Hormonal induction of the mouse mammary tumour virus (MMTV) promoter is mediated by interactions between hormone receptors and other transcription factors bound to a complex array of sites. Previous results suggested that access to these sites is modulated by their precise organization into a positioned regulatory nucleosome. Using genomic footprinting, we show that MMTV promoter DNA is rotationally phased in intact cells containing either episomal or chromosomally integrated proviral fragments. Prior to induction there is no evidence for factors bound to the promoter. Following progesterone induction of cells with high levels of receptor, genomic footprinting detects simultaneous protection over the binding sites for hormone receptors, NF-I and the octamer binding proteins. Glucocorticoid or progestin induction leads to a characteristic chromatin remodelling that is independent of ongoing transcription. The centre of the regulatory nucleosome becomes more accessible to DNase I and restriction enzymes, but the limits of the nucleosome are unchanged and the 145 bp core region remains protected against micrococcal nuclease digestion. Thus, the nucleosome covering the MMTV promoter is neither removed nor shifted upon hormone induction, and all relevant transcription factors bind to the surface of the rearranged nucleosome. Since these factors cannot bind simultaneously to free DNA, maintainance of the nucleosome may be required for binding of factors to contiguous sites. Images PMID:7737125

  19. Action of luteinizing hormone-releasing hormone: involvement of novel arachidonic acid metabolites.

    PubMed Central

    Snyder, G D; Capdevila, J; Chacos, N; Manna, S; Falck, J R

    1983-01-01

    Anterior pituitary cells were incubated in the presence of luteinizing hormone-releasing hormone and one of three inhibitors of arachidonic acid metabolism:indomethacin, an inhibitor of the cyclooxygenase system; nordihydroguaiaretic acid, an antioxidant that inhibits lipoxygenase; and icosatetraynoic acid, an acetylenic analogue of arachidonic acid that blocks all known pathways of arachidonic acid metabolism. Indomethacin was ineffective in blocking luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Nordihydroguaiaretic acid was only marginally capable of inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone secretion. Icosatetraynoic acid at 10 microM completely inhibited stimulated luteinizing hormone secretion. Addition of several epoxygenated arachidonic acid metabolites to cells in vitro resulted in secretion of luteinizing hormone equal to or greater than that induced by 10 nM luteinizing hormone-releasing hormone. The half-maximal effective dose for these compounds was approximately 50 nM. The 5,6-epoxyicosatrienoic acid was the most potent of the compounds tested. These studies suggest that luteinizing hormone-releasing hormone-stimulated luteinizing hormone release is closely coupled with the production of oxidized arachidonic acid metabolites. Moreover, one or more of the epoxygenated arachidonic acid metabolites might be a component of the cascade of reactions initiated by luteinizing hormone-releasing hormone that ultimately results in secretion of luteinizing hormone. PMID:6344087

  20. Developmental and hormone-induced epigenetic changes to estrogen and progesterone receptor genes in brain are dynamic across the life span.

    PubMed

    Schwarz, Jaclyn M; Nugent, Bridget M; McCarthy, Margaret M

    2010-10-01

    Sexual differentiation of the rodent brain occurs during a perinatal critical period when androgen production from the male testis is locally converted to estradiol in neurons, resulting in masculinization of adult sexual behavior. Adult brain responses to hormones are programmed developmentally by estradiol exposure, but the mechanism(s) by which these changes are permanently organized remains poorly understood. Activation of steroid receptors plays a major role in organization of the brain, and we hypothesized that estradiol-induced alteration of steroid-receptor gene methylation is a critical component to this process. Estrogen receptor (ER)-α and ER-β and progesterone receptor are expressed at high levels within the preoptic area (POA) and the mediobasal hypothalamus, two brain regions critical for the expression of male and female sexual behavior. The percent methylation on the ER-α promoter increased markedly across development. During the critical period of sexual differentiation, females had significantly increased methylation than males or females masculinized with estradiol at two CpG sites. By adulthood, the neonatal sex difference and hormonal modulation of methylation were replaced with a new pattern at a different CpG site on the ER-α promoter. In contrast, the percent methylation on the progesterone receptor and ER-β promoter did not change developmentally but was modulated by hormones and exhibited only late emerging transient sex differences. These data indicate that sex differences in the methylation pattern of genes important for sexual behavior are epigenetically modified during development, but the specific changes observed do not endure and are not necessarily temporally associated with neonatal hormone exposure.

  1. Gonadotropins and Growth Hormone Family Characterization in an Endangered Siluriform Species, Steindachneridion parahybae (Pimelodidae): Relationship With Annual Reproductive Cycle and Induced Spawning in Captivity.

    PubMed

    Honji, Renato Massaaki; Caneppele, Danilo; Pandolfi, Matias; Nostro, Fabiana Laura Lo; Moreira, Renata Guimarães

    2015-09-01

    The aim of this study was to identify and characterize pituitary cells of Steindachneridion parahybae females in captivity, highlighting the possible relationship with reproductive disorders at this level, since this species shows oocyte final maturation, ovulation and spawning dysfunction in captivity. The localization and distribution of growth hormone (GH), prolactin (PRL), somatolactin (SL), β-luteinizing hormone (β-LH), and β-follicle stimulating hormone (β-FSH) immunoreactive (-ir) cells in the adenohypophysis was studied by immunohistochemical and Western blot methods. In addition, cellular morphometric analyses and semi-quantification of ir-cells optical density (OD) during the annual reproductive cycle and after artificial induced spawning (AIS) were performed. Results showed that the distribution and general localization of pituitary cell types were similar to that of other teleost species. However, the morphometrical study of adenohypophysial cells showed differences along the reproductive cycle and following AIS. In general, females at the vitellogenic stage presented greater OD values for GH, PRL and SL than at other maturation stages (previtellogenic and regression stages), probably indicating an increased cellular activity during this stage. Conversely, β-LH OD did not vary during the annual reproductive cycle. After AIS, β-LH, SL and GH ir-cells showed an increase in OD values suggesting a possible involvement on oocyte final maturation, ovulation and spawning or a feedback control on the brain-pituitary-gonads axis. Reproductive dysfunction in S. parahybae females in captivity may be due to alteration of the synthesis pathways of β-LH. In addition, GH family of hormones could modulate associated mechanisms that influence the reproductive status in this species.

  2. Protein Hormones and Immunity‡

    PubMed Central

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  3. Multidirectional chemical signalling between Mammalian hosts, resident microbiota, and invasive pathogens: neuroendocrine hormone-induced changes in bacterial gene expression.

    PubMed

    Karavolos, Michail H; Khan, C M Anjam

    2014-01-01

    Host-pathogen communication appears to be crucial in establishing the outcome of bacterial infections. There is increasing evidence to suggest that this communication can take place by bacterial pathogens sensing and subsequently responding to host neuroendocrine (NE) stress hormones. Bacterial pathogens have developed mechanisms allowing them to eavesdrop on these communication pathways within their hosts. These pathogens can use intercepted communication signals to adjust their fitness to persist and cause disease in their hosts. Recently, there have been numerous studies highlighting the ability of NE hormones to act as an environmental cue for pathogens, helping to steer their responses during host infection. Host NE hormone sensing can take place indirectly or directly via bacterial adrenergic receptors (BARs). The resulting changes in bacterial gene expression can be of strategic benefit to the pathogen. Furthermore, it is intriguing that not only can bacteria sense NE stress hormones but they are also able to produce key signalling molecules known as autoinducers. The rapid advances in our knowledge of the human microbiome, and its impact on health and disease highlights the potential importance of communication between the microbiota, pathogens and the host. It is indeed likely that the microbiota input significantly in the neuroendocrinological homeostasis of the host by catabolic, anabolic, and signalling processes. The arrival of unwanted guests, such as bacterial pathogens, clearly has a major impact on these delicately balanced interactions. Unravelling the pathways involved in interkingdom communication between invading bacterial pathogens, the resident microbiota, and hosts, may provide novel targets in our continuous search for new antimicrobials to control disease.

  4. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: An in vitro study with cells expressing cloned human growth hormone secretagogue receptor.

    PubMed

    Tagami, Keita; Kashiwase, Yohei; Yokoyama, Akinobu; Nishimura, Hitomi; Miyano, Kanako; Suzuki, Masami; Shiraishi, Seiji; Matoba, Motohiro; Ohe, Yuichiro; Uezono, Yasuhito

    2016-08-01

    The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified. In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10(-7) and 10(-6)mol/L enhanced ghrelin-induced (10(-10)-10(-8)mol/L) GHS-R activation. A Ca(2+) imaging assay revealed that olanzapine (10(-7) and 10(-6)mol/L) enhanced ghrelin (10(-7) M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca(2+) imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling.

  5. 4 weeks of high-intensity interval training does not alter the exercise-induced growth hormone response in sedentary men.

    PubMed

    Sasaki, Hiroto; Morishima, Takuma; Hasegawa, Yuta; Mori, Ayaka; Ijichi, Toshiaki; Kurihara, Toshiyuki; Goto, Kazushige

    2014-01-01

    This study determined the effects of high-intensity interval training on the exercise-induced growth hormone (GH) responses, whole body and regional fat content. Twenty-four sedentary males were randomized to either a high-intensity interval training (HIT) group or a low-intensity continuous training (LT) group. The HIT group performed intermittent exercises at 85% of [Formula: see text], whereas the LT group performed continuous exercise for 22 min at 45% of [Formula: see text]. Before and after 4 weeks of training, hormonal and metabolic responses to acute exercise were determined. Acute exercise significantly increased GH concentrations in both groups (p < 0.05). However, the responses did not change after training period in either group. Furthermore, the training did not significantly affect intramyocellular or intrahepatic lipid content in either group. The present study indicates that 4 weeks of high-intensity interval training does not alter the exercise-induced GH responses, whole body fat mass or intramyocellular and intrahepatic lipid content in sedentary males.

  6. Silencing the expression of mitochondrial acyl-CoA thioesterase I and acyl-CoA synthetase 4 inhibits hormone-induced steroidogenesis.

    PubMed

    Maloberti, Paula; Castilla, Rocío; Castillo, Fernanda; Cornejo Maciel, Fabiana; Mendez, Carlos F; Paz, Cristina; Podestá, Ernesto J

    2005-04-01

    Arachidonic acid and its lypoxygenated metabolites play a fundamental role in the hormonal regulation of steroidogenesis. Reduction in the expression of the mitochondrial acyl-CoA thioesterase (MTE-I) by antisense or small interfering RNA (siRNA) and of the arachidonic acid-preferring acyl-CoA synthetase (ACS4) by siRNA produced a marked reduction in steroid output of cAMP-stimulated Leydig cells. This effect was blunted by a permeable analog of cholesterol that bypasses the rate-limiting step in steroidogenesis, the transport of cholesterol from the outer to the inner mitochondrial membrane. The inhibition of steroidogenesis was overcome by addition of exogenous arachidonic acid, indicating that the enzymes are part of the mechanism responsible for arachidonic acid release involved in steroidogenesis. Knocking down the expression of MTE-I leads to a significant reduction in the expression of steroidogenic acute regulatory protein. This protein is induced by arachidonic acid and controls the rate-limiting step. Overexpression of MTE-I resulted in an increase in cAMP-induced steroidogenesis. In summary, our results demonstrate a critical role for ACS4 and MTE-I in the hormonal regulation of steroidogenesis as a new pathway of arachidonic acid release different from the classical phospholipase A2 cascade.

  7. Effect of sex differences and gonadal hormones on kainic acid-induced neurodegeneration in the bed nucleus of the stria terminalis of the rat.

    PubMed

    Pereno, German Leandro; Balaszczuk, Verónica; Beltramino, Carlos Alberto

    2012-05-01

    Previously we have demonstrated that medial nucleus of the amygdala, which is part of medial extended amygdala, is damaged by status epilepticus induced by kainic acid (KA) and this neurodegeneration was prevents by estrogen replacement. The medial bed nucleus of stria terminalis (BSTM) also belong to medial extended amygdala and it is uncertain whether the gonadal hormones are protective or not against this neurotoxicity in the BSTM. Here we show that a single i.p. injection of KA (9 mg/kg) induces neurodegeneration in the subnuclei of the BSTM of rats with different degrees of intensity in males and females. A differential neuroprotective effect of the gonadal hormones was also observed. In diestrous rats, massive neuronal death similar to that in the ovariectomized females was detected. BSTM neurons of proestrous rats, like the ovariectomized treated with estrogen, were significantly less affected by the KA. Testosterone produced a mild neuroprotective action, but dihydrotestosterone did not protect. A similar pattern was observed in all male groups. This results show that estrogen protects BSTM neurons from KA neurotoxicity and androgens are partially neuroprotective; and probably this effect of androgens is due to conversion to estrogen.

  8. 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

  9. Steroid hormones block amyloid fibril-induced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan exocytosis: relationship to neurotoxicity.

    PubMed

    Liu, Y; Schubert, D

    1998-12-01

    Perhaps the most reproducible early event induced by the interaction of amyloid beta peptide (A beta) with the cell is the inhibition of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. We recently demonstrated that cytotoxic amyloid peptides such as A beta and human amylin inhibit cellular MTT reduction by dramatically enhancing MTT formazan exocytosis. We now show the following: (a) Insulin and glucagon, when converted to fibrils with beta-pleated sheet structure, induce MTT formazan exocytosis that is indistinguishable from that induced by A beta. NAC35, an amyloidogenic fragment of alpha-synuclein (or NACP), also induces MTT formazan exocytosis. (b) All protein fibrils with the beta-pleated sheet structure examined are toxic to rat hippocampal neurons. (c) Many sterol sex hormones (e.g., estradiol and progesterone) block amyloid fibril-enhanced MTT formazan exocytosis as well as MTT formazan exocytosis in control cells by acting at a common late step in the exocytic pathway. Steroids fail, however, to protect hippocampal neurons from acute amyloid fibril toxicity. These findings suggest that the ability to enhance MTT formazan exocytosis and to induce neurotoxicity are common biological activities of protein fibrils with beta-pleated sheet structure but that enhanced MTT formazan exocytosis is not sufficient for acute A beta neurotoxicity.

  10. A novel action of follicle-stimulating hormone in the ovary promotes estradiol production without inducing excessive follicular growth before puberty

    PubMed Central

    François, Charlotte M.; Petit, Florence; Giton, Frank; Gougeon, Alain; Ravel, Célia; Magre, Solange; Cohen-Tannoudji, Joëlle; Guigon, Céline J.

    2017-01-01

    In cyclic females, FSH stimulates ovarian estradiol (E2) production and follicular growth up to the terminal stage. A transient elevation in circulating FSH and E2 levels occurs shortly after birth. But what could be the action of FSH on the ovary during this period, and in particular how it stimulates ovarian steroidogenesis without supporting terminal follicular maturation is intriguing. By experimentally manipulating FSH levels, we demonstrate in mice that the mid-infantile elevation in FSH is mandatory for E2 production by the immature ovary, but that it does not stimulate follicle growth. Importantly, FSH increases aromatase expression to stimulate E2 synthesis, however it becomes unable to induce cyclin D2, a major driver of granulosa cell proliferation. Besides, although FSH prematurely induces luteinizing hormone (LH) receptor expression in granulosa cells, LH pathway is not functional in these cells to induce their terminal differentiation. In line with these results, supplying infantile mice with a superovulation regimen exacerbates E2 production, but it does not stimulate the growth of follicles and it does not induce ovulation. Overall, our findings unveil a regulation whereby high postnatal FSH concentrations ensure the supply of E2 required for programming adult reproductive function without inducing follicular maturation before puberty.

  11. [Growth hormone signaling pathways].

    PubMed

    Zych, Sławomir; Szatkowska, Iwona; Czerniawska-Piatkowska, Ewa

    2006-01-01

    The substantial improvement in the studies on a very complicated mechanism-- growth hormone signaling in a cell, has been noted in last decade. GH-induced signaling is characterized by activation of several pathways, including extracellular signal-regulated kinase (ERK), the signal transducer and activator of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review shows a current model of the growth hormone receptor dimerization, rotation of subunits and JAK2 kinase activation as the initial steps in the cascade of events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2 complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and particularly all cascade proteins that activate MAP kinase. These pathways regulate basal cellular functions including target gene transcription, enzymatic activity and metabolite transport. Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too.

  12. L-type calcium channels and MAP kinase contribute to thyrotropin-releasing hormone-induced depolarization in thalamic paraventricular nucleus neurons

    PubMed Central

    Kolaj, Miloslav; Zhang, Li

    2016-01-01

    In rat paraventricular thalamic nucleus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances neuronal excitability via concurrent decrease in a G protein-coupled inwardly rectifying K (GIRK)-like conductance and opening of a cannabinoid receptor-sensitive transient receptor potential canonical (TRPC)-like conductance. Here, we investigated the calcium (Ca2+) contribution to the components of this TRH-induced response. TRH-induced membrane depolarization was reduced in the presence of intracellular BAPTA, also in media containing nominally zero [Ca2+]o, suggesting a critical role for both intracellular Ca2+ release and Ca2+ influx. TRH-induced inward current was unchanged by T-type Ca2+ channel blockade, but was decreased by blockade of high-voltage-activated Ca2+ channels (HVACCs). Both the pharmacologically isolated GIRK-like and the TRPC-like components of the TRH-induced response were decreased by nifedipine and increased by BayK8644, implying Ca2+ influx via L-type Ca2+ channels. Only the TRPC-like conductance was reduced by either thapsigargin or dantrolene, suggesting a role for ryanodine receptors and Ca2+-induced Ca2+ release in this component of the TRH-induced response. In pituitary and other cell lines, TRH stimulates MAPK. In PVT neurons, only the GIRK-like component of the TRH-induced current was selectively decreased in the presence of PD98059, a MAPK inhibitor. Collectively, the data imply that TRH-induced depolarization and inward current in PVT neurons involve both a dependency on extracellular Ca2+ influx via opening of L-type Ca2+ channels, a sensitivity of a TRPC-like component to intracellular Ca2+ release via ryanodine channels, and a modulation by MAPK of a GIRK-like conductance component. PMID:27009047

  13. Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation.

    EPA Science Inventory

    Ozone, a major component of smog generated through the interaction of light and anthropogenic emissions, induces adverse pulmonary, cardiovascular, and systemic health effects upon inhalation. It is generally accepted that ozone-induced lung injury is mediated by its interaction ...

  14. Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess.

    PubMed

    Barbour, Linda A; Mizanoor Rahman, Shaikh; Gurevich, Inga; Leitner, J Wayne; Fischer, Stephanie J; Roper, Michael D; Knotts, Trina A; Vo, Yen; McCurdy, Carrie E; Yakar, Shoshana; Leroith, Derek; Kahn, C Ronald; Cantley, Lewis C; Friedman, Jacob E; Draznin, Boris

    2005-11-11

    Insulin resistance is a cardinal feature of normal pregnancy and excess growth hormone (GH) states, but its underlying mechanism remains enigmatic. We previously found a significant increase in the p85 regulatory subunit of phosphatidylinositol kinase (PI 3-kinase) and striking decrease in IRS-1-associated PI 3-kinase activity in the skeletal muscle of transgenic animals overexpressing human placental growth hormone. Herein, using transgenic mice bearing deletions in p85alpha, p85beta, or insulin-like growth factor-1, we provide novel evidence suggesting that overexpression of p85alpha is a primary mechanism for skeletal muscle insulin resistance in response to GH. We found that the excess in total p85 was entirely accounted for by an increase in the free p85alpha-specific isoform. In mice with a liver-specific deletion in insulin-like growth factor-1, excess GH caused insulin resistance and an increase in skeletal muscle p85alpha, which was completely reversible using a GH-releasing hormone antagonist. To understand the role of p85alpha in GH-induced insulin resistance, we used mice bearing deletions of the genes coding for p85alpha or p85beta, respectively (p85alpha (+/-) and p85beta(-/-)). Wild type and p85beta(-/-) mice developed in vivo insulin resistance and demonstrated overexpression of p85alpha and reduced insulin-stimulated PI 3-kinase activity in skeletal muscle in response to GH. In contrast, p85alpha(+/-)mice retained global insulin sensitivity and PI 3-kinase activity associated with reduced p85alpha expression. These findings demonstrated the importance of increased p85alpha in mediating skeletal muscle insulin resistance in response to GH and suggested a potential role for reducing p85alpha as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle.

  15. 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

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

    PubMed

    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.

  17. 1,2,5,6,9,10-αHexabromocyclododecane (HBCD) impairs thyroid hormone-induced dendrite arborization of Purkinje cells and suppresses thyroid hormone receptor-mediated transcription.

    PubMed

    Ibhazehiebo, Kingsley; Iwasaki, Toshiharu; Shimokawa, Noriaki; Koibuchi, Noriyuki

    2011-03-01

    1,2,5,6,9,10-αHexabromocyclododecane (HBCD) is a nonaromatic, brominated cyclic alkane used as an additive flame retardant. It bioaccumulates, persists in the environment, and has been detected in humans and wildlife. Its developmental neurotoxicity is of great concern. We investigated the effect of HBCD on thyroid hormone (TH) receptor (TR)-mediated transcription using transient transfection-based reporter gene assays and found that a low-dose (10(-10) M) HBCD suppressed TR-mediated transcription. We further examined the effect of HBCD on interaction of TR with TH response element (TRE) and found a partial dissociation of TR from TRE. HBCD did not dissociate steroid receptor coactivator-1 from TR in the presence of TH; neither did it recruit corepressors (N-CoR and SMRT) to TR in the absence of TH. Furthermore, low-dose HBCD (10(-10) M) significantly suppressed TH-induced dendrite arborization of Purkinje cells in primary cerebellar culture derived from newborn rat. These results show that low-dose HBCD can potentially disrupt TR-mediated transactivation and impairs Purkinje cell dendritogenesis, suggesting that HBCD can interfere with TH action in target organs, including the developing brain.

  18. Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary.

    PubMed

    Park, Jae-Il; Kim, Sun-Gyun; Chun, Jang-Soo; Seo, You-Mi; Jeon, Mi-Jin; Ohba, Motoi; Kim, Hyun-Jin; Chun, Sang-Young

    2007-05-30

    We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 microM), but not by low doses RO 31-8220 (0.1-1.0 microM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCzeta activity. Interestingly, like LH, forskolin was also able to activate PKCzeta. Treatment with the cell-permeable PKCzeta-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCzeta. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCzeta pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCzeta in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.

  19. Activation of the MKL1/actin signaling pathway induces hormonal escape in estrogen-responsive breast cancer cell lines.

    PubMed

    Kerdivel, Gwenneg; Boudot, Antoine; Habauzit, Denis; Percevault, Frederic; Demay, Florence; Pakdel, Farzad; Flouriot, Gilles

    2014-06-05

    Estrogen receptor alpha (ERα) is generally considered to be a good prognostic marker because almost 70% of ERα-positive tumors respond to anti-hormone therapies. Unfortunately, during cancer progression, mammary tumors can escape from estrogen control, resulting in resistance to treatment. In this study, we demonstrate that activation of the actin/megakaryoblastic leukemia 1 (MKL1) signaling pathway promotes the hormonal escape of estrogen-sensitive breast cancer cell lines. The actin/MKL1 signaling pathway is silenced in differentiated ERα-positive breast cancer MCF-7 and T47D cell lines and active in ERα-negative HMT-3522 T4-2 and MDA-MB-231 breast cancer cells, which have undergone epithelial-mesenchymal transition. We showed that MKL1 activation in MCF-7 cells, either by modulating actin dynamics or using MKL1 mutants, down-regulates ERα expression and abolishes E2-dependent cell growth. Interestingly, the constitutively active form of MKL1 represses PR and HER2 expression in these cells and increases the expression of HB-EGF, TGFβ, and amphiregulin growth factors in an E2-independent manner. The resulting expression profile (ER-, PR-, HER2-) typically corresponds to the triple-negative breast cancer expression profile.

  20. Lipopolysaccharide Induces a Significant Increase in Expression of Iron Regulatory Hormone Hepcidin in the Cortex and Substantia Nigra in Rat Brain

    PubMed Central

    Wang, Qin; Du, Fang; Qian, Zhong-Ming; Ge, Xiao Hu; Zhu, Li; Yung, Wing Ho; Yang, Lei; Ke, Ya

    2008-01-01

    Hepcidin plays an essential role in maintaining normal iron homeostasis outside the brain. This recently discovered iron regulation hormone is predominantly expressed in the liver, and regulated by iron and hypoxia. As an antimicrobial peptide, this hormone is also elevated during infections and inflammation. In this study we investigated the expression of hepcidin mRNA and protein in different brain regions, including the cortex, hippocampus, striatum, and substantia nigra, and the effects of lipopolysaccharide (LPS) on the expression of hepcidin using quantitative real-time RT-PCR and immunofluorescence analysis. Our data provided further evidence for the existence of hepcidin in all the regions we examined. We also demonstrated for the first time that LPS administration by iv injection can regulate the expression of hepcidin mRNA and protein not only in peripheral organs such as the liver, but also in the brain. LPS induced a significant increase in the expression of hepcidin mRNA and protein in the cortex and substantia nigra, but not in the hippocampus and striatum, indicating a regionally specific regulation of LPS on hepcidin in the brain. The relevant mechanisms and the functions of hepcidin in the brain remain to be elucidated. PMID:18450970

  1. Hormone therapy for transgender patients

    PubMed Central

    2016-01-01

    Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219

  2. Investigation of the effect of α-melanocyte-stimulating hormone on proliferation and early stages of differentiation of human induced pluripotent stem cells.

    PubMed

    Novosadova, E V; Manuilova, E S; Arsenyeva, E L; Andreeva, L A; Lebedeva, O S; Grivennikov, I A; Myasoedov, N F

    2016-03-01

    We have studied the influence of α-melanocyte-stimulating hormone (α-MSH) on proliferation and early stages of differentiation of human induced pluripotent stem cells (iPSc). We have demonstrated that α-MSH receptor genes are expressed in undifferentiated iPSc. The expression levels of MCR1, MCR2, and MCR3 increased at the embryoid body (EB) formation stage. The formation of neural progenitors was accompanied by elevation of MCR2, MCR3, and MCR4 expression. α-MSH had no effect on EB generation and iPSc proliferation at concentrations ranging from 1 nM to 10 μM. At the same time, α-MSH increased the generation of neural rosettes in human iPSc cultures more than twice.

  3. Hormone impostors

    SciTech Connect

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  4. Gonadotropic hormone (GtH) receptors in the testis of the troutSalmo gairdneri: in vitro studies.

    PubMed

    Le Gac, F; Breton, B; Bougoussa, M

    1988-10-01

    A particulate fraction obtained from trout testis at the time of spermiation shows saturable binding sites for(125)I-labeled salmon gonadotropin ((125)I-GtH). Non-gonadal tissues (liver, muscle and spleen) did not demonstrate specific(125)I-GtH binding. The tracer's specific activity was determined by the self-displacement method (18 to 30 μCi/μg). Maximal specific binding ability of(125)I-GtH varied from 20 to 30% of the labelled ligand added, depending on the hormone preparation. Specific binding of(125)I-GtH to 20 mg of the testis membrane varied from 40 to 85% of the total binding depending on the method of membrane prepratation, and was competitively inhibited by concentrations of unlabelled GtH ranging from ca 1 to 1000 ng/ml of incubate. Gonadotropin of mammalian origin, ovine TSH or salmon prolactin competed only weakly, or not at all, for testicular gonadotropin binding sites (relative potencies s-GtH>FSH=hCG>s-PRL>bTSH). Scatchard analysis of equilibrium binding studies shows that saturable gonadotropin binding was due to a class of high affinity binding sites (sites I Ka≊3×10(10) M(-1)) and possibly to a second class of lower affinity binding sites (sites II Ka=5 to 14×10(8) M(-1)). The binding capacity of sites I, as measured in enriched membrane preparations, was 45±18 fmoles/g of testis during the period of spermiation. The concentration of GtH required to obtain half maximal displacement of(125)I-GtH in the binding studies was of the same order of magnitude as the apparent ED50 for GtH stimulation of 11-Cetotestosterone (11KT) secretion by trout testesin vitro. Mammalian LH and FSH were 100 to 1000 folds less potent than salmor GtH to increase 11 KT secretion.

  5. The incorporation of myo-inositol into phosphatidylinositol derivatives is stimulated during hormone-induced meiotic maturation of amphibian oocytes

    SciTech Connect

    Carrasco, D.; Allende, C.C.; Allende, J.E. )

    1990-12-01

    The incorporation of myo-({sup 3}H)inositol into phosphatidylinositol and its phosphorylated derivatives was studied by microinjection of the radioactive precursor into Xenopus laevis oocytes. Induction of meiotic maturation of the oocytes by treatment with either progesterone one or insulin resulted in a significant increase in the incorporation of myo-({sup 3}H)inositol into the phospholipid fraction. This increase occurred 3-6 h after hormonal treatment, a time coincident with the start of the breakdown of the nuclear envelope, and requires protein synthesis. The effect of progesterone and insulin contrasts with the effect of acetylcholine, which acts through a muscarinic receptor causing the activation of phospholipase C, since the latter effector causes an increase in myo-({sup 3}H)inositol incorporation, which is more rapid and does not require protein synthesis. These results suggest that the meiotic maturation process is connected with changes in inositol metabolism in the amphibian oocyte.

  6. Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

    PubMed

    Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

    2016-06-01

    Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future.

  7. E74-like factor inhibition induces reacquisition of hormone sensitiveness decreasing period circadian protein homolog 1 expression in prostate cancer cells☆

    PubMed Central

    Koyama, Kohei; Takahara, Kiyoshi; Inamoto, Teruo; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Komura, Kazumasa; Nishida, Takeshi; Sakamoto, Takeshi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Azuma, Haruhito

    2015-01-01

    Purpose Initiating as an androgen-dependent adenocarcinoma, prostate cancer (PCa) gradually progresses to a castrate-resistant disease following androgen deprivation therapy with a propensity to metastasize. Methods In order to resolve the mechanism of castrate-resistant PCa, we performed a cDNA-microarray assay of two PCa cell lines, LNCaP (androgen dependent) and C4-2 (androgen independent). Among them, we focused on a novel Ets transcription factor, E74-like factor 5 (ELF5), the expression level of which was extremely high in C4-2 in comparison with LNCaP both in the microarray analysis and real-time polymerase chain reaction analysis, and investigated the biological role in acquisition of androgen-refractory PCa growth. Results Western blot analysis and morphological analysis using confocal immunofluorescence microscopy demonstrated that ELF5 was expressed mainly in cytosol both in LNCaP and C4-2. Inhibition of ELF5 expression using ELF5-small interfering RNA in C4-2 induced decreased expression of androgen receptor corepressor, period circadian protein homolog 1, and MTT assay of C4-2 after ELF5 small interfering RNA transfection showed the same cell growth pattern of LNCaP. Conclusions Our in vitro experiments of cell growth and microarray analysis have demonstrated for the first time that decreased expression of period circadian protein homolog 1 due to ELF5 inhibition may induce the possibility of reacquisition of hormone sensitiveness of PCa cells. We suggest that ELF5 could be a novel potential target for the treatment of hormone-refractory PCa patients. PMID:26288799

  8. Rapid signaling responses in Sertoli cell membranes induced by follicle stimulating hormone and testosterone: calcium inflow and electrophysiological changes.

    PubMed

    Loss, Eloísa S; Jacobus, Ana Paula; Wassermann, Guillermo F

    2011-10-10

    This minireview describes the rapid signaling actions of follicle stimulating hormone (FSH) and testosterone in immature Sertoli cells mainly related to Ca(2+) inflow and the electrophysiological changes produced by hormones. The rapid membrane actions of FSH occur in a time frame of seconds to minutes, which include membrane depolarization and the stimulation of (45)Ca(2+) uptake. These effects can be prevented by pertussis toxin (PTX), suggesting that they are likely mediated by Gi-protein coupled receptor activation. Furthermore, these effects were inhibited by verapamil, a blocker of the L-type voltage-dependent Ca(2+) channel (VDCC). Finally, FSH stimulation of (45)Ca(2+) uptake was inhibited by the (phosphoinositide 3-kinase) PI3K inhibitor wortmannin. These results suggest that the rapid action of FSH on L-type Ca(2+) channel activity in Sertoli cells from pre-pubertal rats is mediated by the Gi/Gβγ/PI3Kγ pathway, independent of its effects on insulin-like growth factor type I (IGF-I). Testosterone depolarizes the membrane potential and increases the resistance and the (45)Ca(2+) uptake in Sertoli cells of the seminiferous tubules of immature rats. These actions were nullified by diazoxide (K(+)(ATP) channel opener). Testosterone actions were blocked by both PTX and the phospholipase C (PLC) inhibitor U73122, suggesting the involvement of PLC - phosphatidylinositol 4-5 bisphosphate (PIP2) hydrolysis via the Gq protein in the testosterone-mediated pathway. These results indicate that testosterone acts on the Sertoli cell membrane through the K(+)(ATP) channels and PLC-PIP2 hydrolysis, which closes the channel, depolarizes the membrane and stimulates (45)Ca(2+) uptake. These results demonstrate the existence of rapid non-classical pathways in immature Sertoli cells regulated by FSH and testosterone.

  9. Gamma1- and gamma2-melanocyte stimulating hormones induce central anxiogenic effects and potentiate ethanol withdrawal responses in the elevated plus-maze test in mice.

    PubMed

    Jansone, Baiba; Rumaks, Juris; Dzirkale, Zane; Pupure, Jolanta; Svirskis, Simons; Muceniece, Ruta; Klusa, Vija

    2009-04-01

    Little is known about the endogenous functions of gamma1- and gamma2-melanocyte stimulating hormones (gamma1- and gamma2-MSH). Although gamma-MSHs bind to melanocortin receptor subtypes 3 and 4, we have previously shown that these peptides also influence non-melanocortinergic processes, such as dopaminergic and GABAergic. The aim of this study was to determine the effects of gamma1- and gamma2-MSH (at doses 0.3, 1 and 2 nmol/mouse/5 microl) on the anxiety levels in mice in elevated plus maze. Three experimental paradigms were performed to assess the effects of peptides on: a) ethanol withdrawal; b) acute ethanol-induced anxiolytic action; c) peptides per se. We used ethanol as the model substance, since its action involves either dopaminergic/GABAergic or melanocortinergic processes. gamma-MSHs were administered intracisternally in mice and behavioural responses were assessed in the elevated plus maze test. This study provides the first demonstration of an anxiogenic effect of gamma1- and gamma2-MSH, their synergistic/additive effect on ethanol withdrawal-induced anxiety behaviour, and an antagonism of peptides involved in the anxiolytic action of ethanol. Furthermore, results suggest that gamma-MSHs belong to an anxiogenic peptide family that may play an important role in anxiety disorders as well as in the development of alcohol dependence and/or alcohol withdrawal-induced behaviours.

  10. α-Melanocyte stimulating hormone attenuates dexamethasone-induced osteoblast damages through activating melanocortin receptor 4-SphK1 signaling.

    PubMed

    Guo, Shiguang; Xie, Yue; Fan, Jian-bo; Ji, Feng; Wang, Shouguo; Fei, Haodong

    2016-01-08

    Long-term glucocorticoid (GC) usage may cause non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) is shown to exert potent cytotoxic effect to osteoblasts. Here, we investigated the potential activity of α-melanocyte stimulating hormone (α-MSH) against the process. Our data revealed that pretreatment of α-MSH significantly inhibited Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Melanocortin receptor 4 (MC4R) acts as the receptor of α-MSH in mediating its actions in osteoblasts. The MC4R antagonist SHU9119, or shRNA-mediated knockdown of MC4R, almost abolished α-MSH-induced activation of downstream signalings (Akt and Erk1/2) and its pro-survival effect in osteoblasts. Further studies showed that α-MSH activated MC4R downstream sphingosine kinase 1 (SphK1) and increased cellular sphingosine-1-phosphate (S1P) content in MC3T3-E1 cells and primary murine osteoblasts, which were blocked by SHU9119 or MC4R shRNAs. SphK1 inhibition by the its inhibitor N,N-dimethylsphingosine (DMS), or SphK1 knockdown by targeted-shRNAs, largely attenuated α-MSH-mediated osteoblast protection against Dex. Together, these results suggest that α-MSH alleviates Dex-induced damages to cultured osteoblasts through activating MC4R-SphK1 signaling.

  11. Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila melanogaster.

    PubMed Central

    Lee, Gyunghee; Park, Jae H

    2004-01-01

    Adipokinetic hormones (AKHs) are metabolic neuropeptides, mediating mobilization of energy substrates from the fat body in many insects. In delving into the roles of the Drosophila Akh (dAkh) gene, its developmental expression patterns were examined and the physiological functions of the AKH-producing neurons were investigated using animals devoid of AKH neurons and ones with ectopically expressing dAkh. The dAkh gene is expressed exclusively in the corpora cardiaca from late embryos to adult stages. Projections emanating from the AKH neurons indicated that AKH has multiple target tissues as follows: the prothoracic gland and aorta in the larva and the crop and brain in the adult. Studies using transgenic manipulations of the dAkh gene demonstrated that AKH induced both hypertrehalosemia and hyperlipemia. Starved wild-type flies displayed prolonged hyperactivity prior to death; this novel behavioral pattern could be associated with food-searching activities in response to starvation. In contrast, flies devoid of AKH neurons not only lacked this type of hyperactivity, but also displayed strong resistance to starvation-induced death. From these findings, we propose another role for AKH in the regulation of starvation-induced foraging behavior. PMID:15166157

  12. Fasting-induced changes in hepatic thyroid hormone metabolism in male rats are independent of autonomic nervous input to the liver.

    PubMed

    de Vries, E M; Eggels, L; van Beeren, H C; Ackermans, M T; Kalsbeek, A; Fliers, E; Boelen, A

    2014-12-01

    During fasting, profound changes in the regulation of the hypothalamus-pituitary-thyroid axis occur in order to save energy and limit catabolism. In this setting, serum T3 and T4 are decreased without an appropriate TSH and TRH response reflecting central down-regulation of the hypothalamus-pituitary-thyroid axis. Hepatic thyroid hormone (TH) metabolism is also affected by fasting, because type 3 deiodinase (D3) is increased, which is mediated by serum leptin concentrations. A recent study showed that fasting-induced changes in liver TH sulfotransferases (Sults) and uridine 5'-diphospho-glucuronosyltransferase (Ugts) depend on a functional melanocortin system in the hypothalamus. However, the pathways connecting the hypothalamus and the liver that induce these changes are currently unknown. In the present study, we investigated in rats whether the fasting-induced changes in hepatic TH metabolism are regulated by the autonomic nervous system. We selectively cut either the sympathetic or the parasympathetic input to the liver. Serum and liver TH concentrations, deiodinase expression, and activity and Sult and Ugt expression were measured in rats that had been fasted for 36 hours or were fed ad libitum. Fasting decreased serum T3 and T4 concentrations, whereas intrahepatic TH concentrations remained unchanged. D3 expression and activity increased, as was the expression of constitutive androstane receptor, Sult1b1, and Ugt1a1, whereas liver D1 was unaffected. Neither sympathetic nor parasympathetic denervation affected the fasting-induced alterations. We conclude that fasting-induced changes in liver TH metabolism are not regulated via the hepatic autonomic input in a major way and more likely reflect a direct effect of humoral factors on the hepatocyte.

  13. Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

    PubMed

    Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

    2011-01-01

    Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth.

  14. Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis.

    PubMed

    Maasalu, Katre; Laius, Ott; Zhytnik, Lidiia; Kõks, Sulev; Prans, Ele; Reimann, Ene; Märtson, Aare

    2017-01-01

    Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis, with the aim of finding different gene expressions and thus targets for future osteoporosis biomarker studies. Our study consisted of transcriptome analysis of whole blood serum from 12 elderly female osteoporotic patients and 12 non-osteoporotic elderly female controls. The transcriptome analysis was performed with RNA sequencing technology. For data analysis, the edgeR package of R Bioconductor was used. Two hundred and fourteen genes were expressed differently in osteoporotic compared with non-osteoporotic patients. Statistical analysis revealed 20 differently expressed genes with a false discovery rate of less than 1.47 × 10(-4) among osteoporotic patients. The expression of 10 genes were up-regulated and 10 down-regulated. Further statistical analysis identified a potential osteoporosis mRNA biomarker pattern consisting of six genes: CACNA1G, ALG13, SBK1, GGT7, MBNL3, and RIOK3. Functional ingenuity pathway analysis identified the strongest candidate genes with regard to potential involvement in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers.

  15. 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.

  16. Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction

    PubMed Central

    Trivieri, Maria Giovanna; Oudit, Gavin Y.; Sah, Rajan; Kerfant, Benoit-Gilles; Sun, Hui; Gramolini, Anthony O.; Pan, Yan; Wickenden, Alan D.; Croteau, Walburga; Morreale de Escobar, Gabriella; Pekhletski, Roman; St. Germain, Donald; MacLennan, David H.; Backx, Peter H.

    2006-01-01

    Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na+/Ca2+ exchanger, β-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca2+ cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload. PMID:16595628

  17. Molecular and functional characterization of catfish (Heteropneustes fossilis) aquaporin-1b: changes in expression during ovarian development and hormone-induced follicular maturation.

    PubMed

    Chaube, Radha; Chauvigné, François; Tingaud-Sequeira, Angèle; Joy, Keerikkattil P; Acharjee, Arup; Singh, Varsha; Cerdà, Joan

    2011-01-01

    The oocytes of the freshwater catfish Heteropneustes fossilis hydrate during hormone-induced meiotic maturation. To investigate if this process may be mediated by aquaporins (AQPs), as it occurs in marine fish producing highly hydrated eggs, the cloning of ovarian AQPs in catfish was carried out. Using degenerate primers for conserved domains of the major intrinsic protein (MIP) family, and 5' and 3'end amplification procedures, a full-length cDNA encoding for an AQP1-like protein was isolated. The predicted protein showed the typical six transmembrane domains and two Asn-Pro-Ala (NPA) motifs conserved among the members of the AQP superfamily. Phylogenetic analysis indicated that the catfish AQP clustered with the teleost-specific aquaporin-1b subfamily, and accordingly it was termed HfAqp1b. Heterologous expression in Xenopus laevis oocytes indicated that HfAqp1b encoded for a functional AQP, water permeability being enhanced by cAMP. Site-directed mutagenesis revealed that cAMP induced the translocation of HfAqp1b into the oocyte plasma membrane most likely through the phosphorylation of HfAqp1b Ser(227). In adult catfish, hfaqp1b transcripts were detected exclusively in ovary and brain and showed significant seasonal variations; in the ovary, hfaqp1b was maximally expressed during the pre-spawning period, whereas in the brain the highest expression was detected during spawning. In vitro stimulation of isolated catfish ovarian follicles with vasotocin (VT) or human chorionic gonadotropin (hCG), which induce oocyte maturation and hydration, elevated the hfaqp1b transcript levels after 6 or 16 h of incubation, respectively. These results suggest that HfAqp1b may play a role during VT- and hCG-induced oocyte hydration in catfish, and that VT may regulate HfAqp1b at the transcriptional and post-translational level in a manner similar to the vasopressin-dependent mammalian AQP2.

  18. Exogenous NO depletes Cd-induced toxicity by eliminating oxidative damage, re-establishing ATPase activity, and maintaining stress-related hormone equilibrium in white clover plants.

    PubMed

    Liu, S L; Yang, R J; Pan, Y Z; Wang, M H; Zhao, Y; Wu, M X; Hu, J; Zhang, L L; Ma, M D

    2015-11-01

    Various nitric oxide (NO) regulators [including the NO donor sodium nitroprusside (SNP), the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), the NO-synthase inhibitor N (G)-nitro-L-Arg-methyl ester (L-NAME), and the SNP analogues sodium nitrite/nitrate and sodium ferrocyanide] were investigated to elucidate the role of NO in white clover (Trifolium repens L.) plants after long-term (5 days) exposure to cadmium (Cd). A dose of 100 μM Cd stress significantly restrained plant growth and decreased the concentrations of chlorophyll and NO in vivo, whereas it disrupted the balance of stress-related hormones and enhanced the accumulation of Cd, thereby inducing reactive oxygen species (ROS) burst. However, the inhibition of plant growth was relieved by 50 μM SNP through its stimulation of ROS-scavenging compounds (ascorbic acid, ascorbate peroxidase, catalase, glutathione reductase, non-protein thiol, superoxide dismutase, and total glutathione), regulation of H(+)-ATPase activity of proton pumps, and increasing jasmonic acid and proline but decreasing ethylene in plant tissues. Even so, the alleviating effect of SNP on plant growth was counteracted by cPTIO and L-NAME and was not observed with SNP analogues, suggesting that the protective roles of SNP are related to the induction of NO. These results suggest that NO may improve the Cd tolerance of white clover plants by eliminating oxidative damage, re-establishing ATPase activity, and maintaining hormone equilibrium. Improving our understanding of the role of NO in white clover plants is key to expanding the plantations to various regions and the recovery of pasture species in the future.

  19. Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

    PubMed Central

    Mitra, Swarup; Bastos, Cristiane P.; Bates, Katherine; Pereira, Grace S.; Bult-Ito, Abel

    2016-01-01

    There is currently a lack of understanding of how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female obsessive-compulsive disorder (OCD) patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2) or progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background. PMID:27881956

  20. Nitrite-induced alterations in sex steroids and thyroid hormones of Labeo rohita juveniles: effects of dietary vitamin E and L-tryptophan.

    PubMed

    Ciji, A; Sahu, N P; Pal, A K; Akhtar, M S

    2013-10-01

    An experiment was conducted to study the effect of sub-lethal nitrite exposure on sex steroids (testosterone and estradiol), cortisol and thyroid hormones (T3 and T4) of Labeo rohita juveniles. Fishes previously fed with normal or elevated levels of vitamin E (VE) and tryptophan for 60 days were exposed to sub-lethal nitrite for another 45 days with same feeding regime. There were nine treatment groups, viz. VE0TRP0-N, VE0TRP0+N, VE100TRP0-N, VE100TRP0+N, VE100TRP0.75+N, VE100TRP1.5+N, VE150TRP0+N, VE300TRP0+N and VE200TRP1+N. Except the groups VE0TRP0-N and VE100TRP0-N, all other groups were exposed to nitrite. At the end of the 45 days of nitrite exposure, serum samples were assayed for sex steroids, cortisol and thyroid hormones. The serum T3 and T4 levels decreased to the extent of 84.5 and 94.06%, respectively, upon nitrite exposure. Dietary supplementation with additional amounts of VE and tryptophan appears to reduce the decline of the production of T4. The serum testosterone and estradiol decreased 97.31 and 92.86%, respectively, upon nitrite exposure. Supplementation with additional amounts of VE was found to reverse nitrite-induced inhibition of testosterone and estradiol production. Serum cortisol increased upon nitrite exposure and unexposed (VE100-N) group showed lower levels, which were comparable to groups fed with elevated levels of VE. The overall results of the present study revealed that environmental nitrites have a negative impact on steroidogenesis, which can be overcome by dietary supplementation of elevated amounts of VE (minimum of 150 mg VE Kg diet(-1)) and to a lesser extent by tryptophan (only at the level of 1.5% of the diet).

  1. Molecular modulation of estrogen-induced apoptosis by synthetic progestins in hormone replacement therapy: An insight into the Women’s Health Initiative study

    PubMed Central

    Sweeney, Elizabeth; Fan, Ping; Jordan, Virgil Craig

    2014-01-01

    Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women, and can comprise an estrogen alone or an estrogen combined with a progestin. The Women’s Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in post-menopausal women, while combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the post-menopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone (Dex) increases GR transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, up-regulating ER-target genes and generating apoptosis in MCF-7:5C cells. The data suggests that women taking HRT comprising an estrogen plus MPA may have an increased the risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g. NETA) should be considered as alternatives to MPA. PMID:25304262

  2. FOXL2 Is an Essential Activator of SF-1-Induced Transcriptional Regulation of Anti-Müllerian Hormone in Human Granulosa Cells

    PubMed Central

    Park, Si Eun; Lee, Seunghwa; Park, Mira; Bae, Jeehyeon

    2016-01-01

    Anti-Müllerian hormone (AMH) is required for proper sexual differentiation by regulating the regression of the Müllerian ducts in males. Recent studies indicate that AMH could be an important factor for maintaining the ovarian reserve. However, the mechanisms of AMH regulation in the ovary are largely unknown. Here, we provide evidence that AMH is an ovarian target gene of steroidogenic factor-1 (SF-1), an orphan nuclear receptor required for proper follicle development. FOXL2 is an evolutionally conserved transcription factor, and its mutations cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), wherein affected females display eyelid defects and premature ovarian failure (POF). Notably, we found that functional FOXL2 is essential for SF-1-induced AMH regulation, via protein–protein interactions between FOXL2 and SF-1. A BPES-inducing mutant of FOXL2 (290–291delCA) was unable to interact with SF-1 and failed to mediate the association between SF-1 and the AMH promoter. Therefore, this study identified a novel regulatory circuit for ovarian AMH production; specifically, through the coordinated interplay between FOXL2 and SF-1 that could control ovarian follicle development. PMID:27414805

  3. Protective effect of alpha-melanocyte-stimulating hormone (α-MSH) on the recovery of ischemia/reperfusion (I/R)-induced retinal damage in a rat model.

    PubMed

    Varga, Balazs; Gesztelyi, Rudolf; Bombicz, Mariann; Haines, David; Szabo, Adrienn Monika; Kemeny-Beke, Adam; Antal, Miklos; Vecsernyes, Miklos; Juhasz, Bela; Tosaki, Arpad

    2013-07-01

    The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.

  4. Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during larval intestinal cell death and adult stem cell development.

    PubMed

    Matsuura, Kazuo; Fujimoto, Kenta; Fu, Liezhen; Shi, Yun-Bo

    2012-02-01

    Thyroid hormone (T(3)) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T(3) signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T(3)-dependent Xenopus metamorphosis as a model to study how T(3) regulates transcription during vertebrate development. T(3) exerts its metamorphic effects through T(3) receptors (TR). TR recruits, in a T(3)-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T(3) target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.

  5. Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

    PubMed Central

    Crespo, Diego; Goetz, Frederick W.; Planas, Josep V.

    2015-01-01

    Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID:26374476

  6. Activity changes in jaw motor neurons induced by egg-laying hormone contribute to the feeding suppression during egg-laying behavior in Aplysia kurodai.

    PubMed

    Narusuye, Kenji; Hamaguchi, Aya; Nagahama, Tatsumi

    2013-01-01

    Egg-laying behavior in Aplysia is accompanied by behavioral changes such as feeding suppression. We investigated the effects of the egg-laying hormone (ELH) on food intake, the activity patterns of jaw muscles, and the activity of buccal neurons (multi-action neuron [MA1] and jaw-closing motor neuron [JC2]), which are elements of the feeding neural circuits controlling jaw movements in Aplysia kurodai. Injection of ELH into the body cavity inhibited the intake of seaweed. After ELH application, the rhythmic activity of jaw muscles that was induced by preferred taste stimulation elicited fewer ingestion-like responses and increased the number of rejection-like responses. ELH applied to the buccal ganglia increased the firing activity of JC2 during spontaneous rhythmic responses and during the rhythmic feeding-like responses that were evoked by electrical stimulation of the esophageal nerves. In the 2 types of rhythmic responses, the Dn (normalized value of the delay time of JC2 firing onset) decreased after ELH application as compared with the control. Furthermore, ELH decreased the size of MA1-induced inhibitory postsynaptic currents in JC2. These results suggest that ELH changes the buccal motor program from ingestion to rejection on the basis of our previous results, and may contribute to a decrease in food intake during egg laying.

  7. Brain-derived neurotrophic factor (BDNF) ameliorates the suppression of thyroid hormone-induced granule cell neurite extension by hexabromocyclododecane (HBCD).

    PubMed

    Ibhazehiebo, Kingsley; Iwasaki, Toshiharu; Xu, Ming; Shimokawa, Noriaki; Koibuchi, Noriyuki

    2011-04-08

    Thyroid hormone (TH) plays an essential role in growth and differentiation of the central nervous system. Deficiency of TH during perinatal period results in abnormal brain development known as cretinism in human. We recently reported that an environmental chemical 1,2,5,6,9,10-α-hexabromocyclododecane (HBCD) suppressed TH receptor (TR)-mediated transcription. To examine the effect of HBCD on cerebellar granule cells, we used purified rat cerebellar granule cells in reaggregate culture. Low dose HBCD (10(-10)M) significantly suppressed TH-induced neurite extension of granule cell aggregate. To clarify further the mechanisms of such suppression, we added brain-derived neurotrophic factor (BDNF) into culture medium, since BDNF plays a critical role in promoting granule cell development and is regulated by TH. BDNF completely rescued HBCD-induced suppression of granule cell neurite extension in the presence of T3. These results indicate that HBCD may disrupt TH-mediated brain development at least in part due to a disruption of the T3 stimulated increase in BDNF and BDNF may possess ability to ameliorate the effect of HBCD in granule cells.

  8. Role of alpha 1- and alpha 2-adrenergic receptors in the growth hormone and prolactin response to insulin-induced hypoglycemia in man.

    PubMed

    Tatár, P; Vigas, M

    1984-09-01

    The effects of intravenous infusion of the nonselective alpha-adrenergic antagonist phentolamine or of the selective alpha 2-adrenergic antagonist yohimbine on growth hormone (GH), prolactin (PRL) and cortisol secretion during insulin-induced hypoglycemia were studied in 11 healthy young men. The GH response was blunted following each antagonist used, PRL secretion was higher after yohimbine and diminished after phentolamine when compared to controls. The plasma cortisol response was not influenced by either compound. In another series of experiments no effect of an oral administration of prazosin, a selective alpha 1-adrenergic antagonist, on the secretion of GH, PRL and cortisol was found in any of 7 subjects. Prazosin inhibited blood pressure increase during hypoglycemia and induced slight drowsiness and fatigue in the subjects. It is concluded that in man alpha-adrenergic stimulation of GH secretion during hypoglycemia is transmitted via alpha 2-receptors, PRL secretion is mediated via alpha 1-receptors, whereas inhibition of PRL release is mediated via alpha 2-receptors. In this experiment no effect of alpha 1- or alpha 2-blockade on cortisol response to hypoglycemia was seen.

  9. Metabolic hormone FGF21 is induced in ground squirrels during hibernation but its overexpression is not sufficient to cause torpor.

    PubMed

    Nelson, Bethany T; Ding, Xunshan; Boney-Montoya, Jamie; Gerard, Robert D; Kliewer, Steven A; Andrews, Matthew T

    2013-01-01

    Hibernation is a natural adaptation that allows certain mammals to survive physiological extremes that are lethal to humans. Near freezing body temperatures, heart rates of 3-10 beats per minute, absence of food consumption, and depressed metabolism are characteristic of hibernation torpor bouts that are periodically interrupted by brief interbout arousals (IBAs). The molecular basis of torpor induction is unknown, however starved mice overexpressing the metabolic hormone fibroblast growth factor 21 (FGF21) promote fat utilization, reduce body temperature, and readily enter torpor-all hallmarks of mammalian hibernation. In this study we cloned FGF21 from the naturally hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus) and found that levels of FGF21 mRNA in liver and FGF21 protein in serum are elevated during hibernation torpor bouts and significantly elevated during IBAs compared to summer active animals. The effects of artificially elevating circulating FGF21 concentrations 50 to 100-fold via adenoviral-mediated overexpression were examined at three different times of the year. This is the first time that a transgenic approach has been used in a natural hibernator to examine mechanistic aspects of hibernation. Surgically implanted transmitters measured various metrics of the hibernation phenotype over a 7-day period including changes in motor activity, heart rate and core body temperature. In April fed-state animals, FGF21 overexpression decreased blood insulin and free fatty acid concentrations, effects similar to those seen in obese mice. However, elevated FGF21 concentrations did not cause torpor in these fed-state animals nor did they cause torpor or affect metabolic parameters in fasted-state animals in March/April, August or October. We conclude that FGF21 is strongly regulated during torpor and IBA but that its overexpression is not sufficient to cause torpor in naturally hibernating ground squirrels.

  10. Genistein-induced histomorphometric and hormone secreting changes in the adrenal cortex in middle-aged rats.

    PubMed

    Ajdzanović, Vladimir; Sosić-Jurjević, Branka; Filipović, Branko; Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Sekulić, Milka; Milosević, Verica

    2009-02-01

    The soybean phytoestrogen, genistein, is increasingly consumed as an alternative therapeutic for age-related diseases, namely cardiovascular conditions, cancer and osteoporosis. Besides estrogenic/antiestrogenic action, this isoflavone exerts a prominent inhibitory effect on tyrosine kinase and the steroidogenic enzyme families, thus affecting hormonal homeostasis. The aim of this study was to examine the effects of genistein on: histomorphometric features of the adrenal cortex, blood concentrations of aldosterone, corticosterone and dehydroepiandrosterone (DHEA) and adrenal tissue corticosterone content in orchidectomized middle-aged male rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for three weeks, while the control groups received the vehicle alone. The adrenal cortex was analysed histologically and morphometrically. Circulating concentrations of aldosterone, corticosterone and DHEA, as well as adrenal tissue corticosterone levels, were determined by immunoassay. When compared to the SO group, orchidectomy decreased the ZG and ZR cell volume by 43% and 29%, respectively (P<0.05). Serum concentrations of aldosterone and DHEA were markedly lower [13% and 41%, respectively (P<0.05)], while serum and adrenal tissue levels of corticosterone did not change after orchidectomy. Orchidectomy followed by genistein treatment increased the ZG, ZF and ZR cell volume by 54%, 34% and 77%, respectively (P<0.05), compared to the untreated orchidectomized group. Histological analysis revealed noticeable vacuolization of the ZG and ZF cells in the Orx+G group. Serum aldosterone and corticosterone concentrations together with adrenal tissue corticosterone were 47%, 31% and 44% lower, respectively (P<0.05), whereas serum DHEA concentration was 342% higher (P<0.05) in this group in comparison with the Orx group. This study

  11. 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.

  12. Intermittent Administration of Parathyroid Hormone [1–34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model

    PubMed Central

    Bi, Fanggang; Shi, Zhongli; Zhou, Chenhe; Liu, An; Shen, Yue; Yan, Shigui

    2015-01-01

    We examined whether intermittent administration of parathyroid hormone [1–34] (PTH[1–34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1–34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1–34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone–implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1–34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1–34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis. PMID:26441073

  13. Hormonally induced alterations of chromatin structure in the polyadenylation and transcription termination regions of the chicken ovalbumin gene.

    PubMed Central

    Bellard, M; Dretzen, G; Bellard, F; Kaye, J S; Pratt-Kaye, S; Chambon, P

    1986-01-01

    We have studied the chromatin structure of a 16-kb region of the chicken genome containing the 3'-terminal 2 kb of the ovalbumin pre-mRNA coding sequence and the 14-kb segment located immediately downstream from the main mRNA polyadenylation site. Using the indirect end-labelling technique, four major and two minor DNase I-hypersensitive regions were found in the oviduct chromatin, whereas they were not present in liver, kidney or erythrocyte chromatin. The first hypersensitive region (region A) was present in chromatin of oviducts from laying hen and estrogen- or progesterone-stimulated immature chicks, in which the ovalbumin gene is expressed, but not in the chromatin of 'acute withdrawn' chicks where the gene is no longer transcribed. Region A spans 1.3 kb, from 7.2 to 8.5 kb downstream from the ovalbumin gene capsite (position +1), and encompasses the 3' moiety of the last exon including the major polyadenylation signal and polyadenylation site located at +7546 and +7564, respectively. Region A also contains a minor polyadenylation signal present at +7294 and the corresponding polyadenylation site at +7368. Two putative termination sequences at +8445 and +8483 are also found at the 3' extremity of region A in a 170-bp DNA segment within which 90% of the ovalbumin primary transcripts apparently terminate. Two minor hormone-independent DNase I-hypersensitive regions (a1 and a2) located at +8.6 and +8.8 kb are also specific to oviduct chromatin.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:3011414

  14. Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

    PubMed

    Bi, Fanggang; Shi, Zhongli; Zhou, Chenhe; Liu, An; Shen, Yue; Yan, Shigui

    2015-01-01

    We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

  15. Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes

    EPA Science Inventory

    Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and cl...

  16. The wound hormone jasmonate

    PubMed Central

    Koo, Abraham J.K.; Howe, Gregg A.

    2009-01-01

    Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic wound responses through distinct cell autonomous and nonautonomous pathways. In both pathways, bioactive JAs are recognized by an F-box protein-based receptor system that couples hormone binding to ubiquitin-dependent degradation of transcriptional repressor proteins. These results provide a new framework for understanding how plants recognize and respond to tissue injury. PMID:19695649

  17. Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway.

    PubMed

    Yang, Xiao; Wang, Jing; Li, Wen-Ping; Jin, Zhi-Jun; Liu, Xiao-Jun

    2015-01-01

    Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (P<0.05). Consistently, the expression of Dsc3 in four out of five ovarian cancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway.

  18. Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

    USGS Publications Warehouse

    Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

    2003-01-01

    Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

  19. Expression of Vascular Endothelial Growth Factor A During Ligand-Induced Down-Regulation of Luteinizing Hormone Receptor in the Ovary☆

    PubMed Central

    Harada, M.; Peegel, H.; Menon, K. M. J.

    2010-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important regulators of ovarian angiogenesis. In this study, we examined the temporal relationship between VEGF-A and luteinizing hormone receptor (LHR) mRNA expression during ligand-induced down-regulation of LHR. Immature female rats were treated with pregnant mare’s serum gonadotropin followed by 25 IU hCG 56h later (day 0). On day 5, treatment with hCG (50 IU) to down-regulate LHR showed a temporal decrease in VEGF-A mRNA and protein levels in parallel with decreasing LHR mRNA. This effect was specific since the expression of CYP11A1 mRNA showed no decline. Examination of VEGF-A mRNA expression, using in situ hybridization histochemistry with 35S-labeled antisense VEGF-A mRNA probe, showed intense signal in the corpora lutea on day 5. Treatment with 50 IU hCG to down-regulate LHR mRNA showed a decline in the intensity of VEGF-A mRNA in the corpora lutea. VEGF-A mRNA expression returned to control level 53 hours later when the expression of LHR mRNA also recovered. These results show that the transient down-regulation of VEGF-A mRNA and protein closely parallels the ligand-induced down-regulation of LHR mRNA. The present study establishes a close association between VEGF-A and LHR mRNA expression, suggesting the possibility that VEGF-A-induced vascularization of the ovary is dictated by the expression of LHR and this might play a regulatory role in ovarian physiology. PMID:20619315

  20. Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause.

    PubMed

    Keck, Maggie; Romero-Aleshire, Melissa J; Cai, Qi; Hoyer, Patricia B; Brooks, Heddwen L

    2007-07-01

    Changes in the estrogen/testosterone balance at menopause may negatively influence the development of diabetic kidney disease. Furthermore, recent studies suggest that changes in hormone levels during perimenopause may influence disease development. Injection of 4-vinylcyclohexene diepoxide (VCD) in B(6)C(3)F(1) mice induces gradual ovarian failure, preserving both the perimenopausal (peri-ovarian failure) and menopausal (post-ovarian failure) periods. To address the impact of the transition into menopause on the development of diabetes and diabetic kidney damage, we used streptozotocin (STZ)-induced diabetes in the VCD model of menopause. After 6 wk of STZ-induced diabetes, blood glucose was significantly increased in post-ovarian failure (post-OF) diabetic mice compared with cycling diabetic mice. In peri-ovarian failure (peri-OF) diabetic mice, blood glucose levels trended higher but were not significantly different from cycling diabetic mice, suggesting a continuum of worsening blood glucose across the menopausal transition. Cell proliferation, an early marker of damage in the kidney, was increased in post-OF diabetic mice compared with cycling diabetic mice, as measured by PCNA immunohistochemistry. In post-OF diabetic mice, mRNA abundance of early growth response-1 (Egr-1), collagen-4alpha1, and matrix metalloproteinase-9 were increased and 3beta-hydroxysteroid dehydrogenase 4 (3beta-HSD4) and transforming growth factor-beta(2) (TGF-beta(2)) were decreased compared with cycling diabetic mice. In peri-OF diabetic mice, mRNA abundance of Egr-1 and 3beta-HSD4 were increased, and TGF-beta(2) was decreased compared with cycling diabetic mice. This study highlights the importance and utility of the VCD model of menopause, as it provides a physiologically relevant system for determining the impact of the menopausal transition on diabetes and diabetic kidney damage.

  1. Adverse Effects of Induced Hot Flashes on Objectively Recorded and Subjectively Reported Sleep: Results of a Gonadotropin-Releasing Hormone Agonist Experimental Protocol

    PubMed Central

    Joffe, Hadine; White, David P.; Crawford, Sybil L.; McCurnin, Kristin E.; Economou, Nicole; Connors, Stephanie; Hall, Janet E.

    2013-01-01

    Objectives The impact of hot flashes on sleep is of great clinical interest, but results are inconsistent, especially when both hot flashes and sleep are measured objectively. Using objective and subjective measurements, we examined the impact of hot flashes on sleep by inducing hot flashes with a gonadotropin-releasing hormone agonist (GnRHa). Methods The GnRHa leuprolide was administered to 20 healthy premenopausal volunteers without hot flashes or sleep disturbances. Induced hot flashes were assessed objectively (skin-conductance monitor) and subjectively (daily diary) during one-month follow-up. Changes from baseline in objective (actigraphy) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were compared between women who did and did not develop objective hot flashes, and, in parallel analyses, subjective hot flashes. Results New-onset hot flashes were recorded in 14 (70%) and reported by 14 (70%) women (80% concordance). Estradiol was universally suppressed. Objective sleep efficiency worsened in women with objective hot flashes and improved in women without objective hot flashes (median decrease 2.6%, increase 4.2%, p=0.005). Subjective sleep quality worsened more in those with than without subjective hot flashes (median increase PSQI 2.5 vs. 1.0, p=0.03). Objective hot flashes were not associated with subjective sleep quality, nor were subjective symptoms linked to objective sleep measures. Conclusions This experimental model of induced hot flashes demonstrates a causal relationship between hot flashes and poor sleep quality. Objective hot flashes result in worse objective sleep efficiency, while subjective hot flashes worsen perceived sleep quality. PMID:23481119

  2. Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.

    PubMed

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

    2014-08-01

    Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, P<0.05), and the effects were dose dependent. Histologically, hair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia.

  3. Network Identification of Hormonal Regulation

    PubMed Central

    Vis, Daniel J.; Westerhuis, Johan A.; Hoefsloot, Huub C. J.; Roelfsema, Ferdinand; van der Greef, Jan

    2014-01-01

    Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for detecting regulatory relations between hormones. This is demonstrated with a cohort of obese women, who underwent blood sampling at 10 minute intervals for 24-hours. The cohort was treated with bromocriptine in an attempt to clarify how hormone relations change by treatment. The detected regulatory relations are summarized in a network graph and treatment-induced changes in the relations are determined. The proposed method identifies many relations, including well-known ones. Ultimately, the method provides ways to improve the description and understanding of normal hormonal relations and deviations caused by disease or treatment. PMID:24852517

  4. Ambiguine I Isonitrile from Fischerella ambigua Induces Caspase-Independent Cell Death in MCF-7 Hormone Dependent Breast Cancer Cells

    PubMed Central

    Acuña, Ulyana Muñoz; Zi, Jiachen; Orjala, Jimmy; Carcache de Blanco, Esperanza J.

    2015-01-01

    Ambiguine I isonitrile (AmbI) obtained from the cultured cyanobacterium Fischerella ambigua was identified as a potent NF-κB inhibitor (IC50=30 nM). The cytotoxic effect was evaluated in both HT-29 colon cancer cell line (EC50=4.35 μM) and MCF-7 breast cancer cell line (EC50=1.7 μM) using the SRB assay. In the cells treated with AmbI, an increased population of cells was detected in sub G1-phase. The apoptotic effect was associated with block in G1-phase of the cell cycle in treated cells; however, cell death was induced independently of caspase-7. The NF-κB expression of p50 and p65 units were also examined in treated cells and compared with the positive control, rocaglamide (IC50=75 nM). Moreover, the expression of mediators of the NF-κB pathway such as kinase IKKκ was studied at increasing concentrations of AmbI. The down stream effect of NF-κB inhibition and the effect on the expression of TNF-α induced ICAM-1 was evaluated. Thus, the dose-dependent and time-dependent effect of AmbI on MCF-7 cells was examined in an attempt to investigate its potential mechanism of action on inducing apoptosis. PMID:26753095

  5. Thiazolidinediones and the renal and hormonal response to water immersion-induced volume expansion in type 2 diabetes mellitus.

    PubMed

    Goenka, Niru; Kotonya, Christina; Penney, Michael D; Randeva, Harpal S; O'Hare, J Paul

    2008-04-01

    Thiazolidinediones cause sodium retention and edema by a direct effect on the kidneys. The aim of this study was to use the technique of head-out water immersion to investigate the effects of rosiglitazone on sodium and volume homeostasis in subjects with type 2 diabetes mellitus. The volume expansion response to water immersion was compared with the response on a non-immersion control day in 12 nondiabetic male subjects and 8 diet-controlled male type 2 diabetic subjects with hourly blood and urine sampling over a 4-h period. This was repeated after both groups had taken 4 mg of rosiglitazone daily for 7 days. Immersion produced a natriuresis in both groups (P < 0.001). An impairment of this natriuresis was seen in the diabetic subjects (P = 0.006). However, when rosiglitazone was taken, there was no significant difference in immersion-induced natriuresis compared with nondiabetic controls (P = 0.2). There was an immersion-induced rise in atrial natriuretic peptide (ANP) and urinary cyclic guanosine monophosphate (cGMP), in the healthy subjects (ANP P = 0.001, cGMP P = 0.043), which was not seen in the diabetic subjects (ANP P = 0.51, cGMP P = 0.74). Rosiglitazone restored the immersion-induced increase in cGMP excretion and rise of ANP in the diabetic group (ANP P = 0.048, cGMP P = 0.009). This study confirms that type 2 diabetic subjects have an impaired natriuretic response to acute volume expansion, which appears to be enhanced rather than diminished by rosiglitazone. This may be related to its effects in increasing natriuretic peptides and restoring the impaired cGMP excretion to volume expansion.

  6. Role of arachidonic acid and protein kinase C during maturation-inducing hormone-dependent meiotic resumption and ovulation in ovarian follicles of Atlantic croaker

    USGS Publications Warehouse

    Patino, R.; Yoshizaki, G.; Bolamba, D.; Thomas, P.

    2003-01-01

    The roles of arachidonic acid (AA) and protein kinase C (PKC) during in vitro maturation-inducing hormone (MIH)-dependent meiotic resumption (maturation) and ovulation were studied in ovarian follicles of Atlantic croaker (Micropogonias undulatus). The requirement for cyclooxygenase (COX) metabolites of AA was examined using a nonspecific COX inhibitor, indomethacin (IM), as well as two COX products, prostaglandin (PG) F2?? and PGE2, whereas the role of lipoxygenase (LOX) was investigated using a specific LOX inhibitor, nordihydroguaiaretic acid (NDGA). The involvement of PKC was examined using phorbol 12-myristate 13-acetate (PMA), a PKC activator, as well as GF109203X (GF), a specific inhibitor of PKC and 1-(5-isoquin- olinesulfonyl)-2-methylpiperazine (H7), nonspecific inhibitor of protein kinases. Genomic mechanisms were examined with the transcription-inhibitor actinomycin D (ActD) and the functionality of heterologous (oocyte-granulosa) gap junctions (GJ) with a dye transfer assay. The AA (100 ??M) and PGF2?? (5 ??M) did not induce maturation, and NDGA (10 ??M) did not affect MIH-dependent maturation. However, IM (100 ??M) partially inhibited MIH-dependent maturation. Conversely, AA and both PGs induced, and IM and NDGA inhibited, MIH-dependent ovulation in matured follicles. The PMA (1 ??g/ml) did not induce maturation but caused ovulation in matured follicles, whereas PKC inhibitors (GF, 5 ??M; H7, 50??M) did not affect MIH-dependent maturation but inhibited MIH- and PMA-dependent ovulation. The PMA-dependent ovulation was inhibited by IM but not by NDGA. In addition, ActD (5 ??M) blocked MIH-dependent, but not PMA-dependent, ovulation, and PGF2?? restored MIH-dependent ovulation in ActD-blocked follicles. The AA and PGs did not induce, and GF did not inhibit, MIH-dependent heterologous GJ uncoupling. In conclusion, AA and PKC mediate MIH-dependent ovulation but not meiotic resumption or heterologous GJ uncoupling in croaker follicles, but a permissive role

  7. Thyroliberin (TRH) induced growth hormone (GH) release: test of maturation of hypothalamo-pituitary axis in postnatal rat.

    PubMed

    Strbák, V; Jurcovicová, J; Vigas, M

    1981-12-01

    Small doses of TRH elicit GH release from rat pituitary provided the pituitary lacks CNS influences (e.g. in vitro or in ectopic pituitaries). We have found previously that hypothalamic regulation of TSH secretion matures between the 5th and 12th postnatal day. Therefore the possibility of TRH induced GH release was investigated in neonatal rats. GH concentration was measured by RIA at 10 min after s.c. TRH administration (4.1 pmol g-1 BW) into female Wistar rats at the age 3, 9, 12, 15, 21, 30 and 100 days. Control animals were injected the same volume (1 microliter g-1 BW) of saline. Serum GH in saline treated animals gradually decreased during postnatal ontogenesis. The TRH induced increase of serum GH level decreased during maturation: the most marked response was found at 3 days, it was somewhat lessened but still significant at 9 days and was absent in 12, 15, 30 days old and adult animals. Surprisingly, in 21 days old animals the increase of GH after TRH administration was again present. We conclude that the ability of TRH to elicit GH release in newborn rats may depend on the maturity of the hypothalamo-pituitary axis. The effect of hypothalamic somatostatin is likely to inhibit such a response at the pituitary level in older rats.

  8. The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

    PubMed Central

    Derkach, Kira V.; Bondareva, Vera M.; Chistyakova, Oxana V.; Berstein, Lev M.; Shpakov, Alexander O.

    2015-01-01

    In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation by β-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications. PMID:26124826

  9. Involvement of glutamate and gamma-aminobutyric acid (GABA)-ergic systems in thyrotropin-releasing hormone-induced rat cerebellar cGMP formation.

    PubMed

    Nakayama, T; Hashimoto, T; Nagai, Y

    1996-12-05

    The increase in cyclic guanosine 3',5'-monophosphate (cGMP) caused by subcutaneous injection of thyrotropin-releasing hormone (TRH) tartrate was observed in a region-specific manner in the rat cerebellum. TRH tartrate (TRH-T) (2.8, 7.0 and 17 mg/kg as free TRH, s.c.) produced dose-dependent increases in cGMP levels markedly in the cerebellar superior and inferior vermis, and a smaller but still significant increase in the cerebellar hemispheres and brainstem but no significant increases in other brain regions. The TRH-induced increase in the cGMP level in the cerebellum was suppressed by pretreatment with muscimol, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one) or MK-801 (dizocilpine maleate) and partially suppressed by atropine but was not suppressed by chlordiazepoxide, oxazepam, phentolamine, propranolol, cyproheptadine, haloperidol, baclofen or DNQX (6,7-dinitroquinoxaline-2,3-dione), suggesting the possible involvement of GABA (gamma-aminobutyric acid)(A)-ergic, N-methyl-D-aspartate (NMDA)-type glutamatergic and cholinergic systems. These results suggest that excitatory amino acids may be involved in the cGMP formation caused by TRH in the cerebellar areas, and that cGMP formation is inhibited by enhancement of GABAA receptor function.

  10. Teleost maturation-inducing hormone, 17,20β-dihydroxypregn-4-en-3-one, peaks after spawning in Tinca tinca.

    PubMed

    Antonopoulou, Efthimia; Tsikliras, Athanassios C; Kocour, Martin; Zlábek, Vladimir; Flajšhans, Martin; Gela, David; Piačková, Veronika; Scott, Alexander P

    2011-06-01

    During an eight month study of the reproductive cycle in two age groups, and in both sexes, of tench (Tinca tinca L.), it was found that plasma concentrations of the presumptive 'maturation inducing hormone (MIH)' 17,20β-dihydroxypregn-4-en-3-one (17,20β-P) did not reach a peak during the spawning season, but as much as two months after spawning had ceased. The cessation of the spawning season was confirmed by histological examination of the gonads and by measurement of 11-ketotestosterone and 17β-estradiol in the plasma of males and females, respectively. Measurements were also made of the 'alternative MIH' 17,20β,21-trihydroxypregn-4-en-3-one in the older fish. However, this steroid did not show the same pattern as 17,20β-P. An assessment was made of the prevalence of primary spermatocytes in the testes of post-spawned fish - to test an alternative hypothesis that 17,20β-P might be involved in the stimulation of meiosis. However, there was no evidence for any increase in testis differentiation post-spawning. In fact the testes became increasingly undifferentiated as the autumn progressed. The role, if any, of this 'unseasonal' peak of 17,20β-P production remains to be determined.

  11. The Epidermal Growth Factor Receptor (EGFR) Inhibitor Gefitinib Reduces but Does Not Prevent Tumorigenesis in Chemical and Hormonal Induced Hepatocarcinogenesis Rat Models

    PubMed Central

    Ribback, Silvia; Sailer, Verena; Böhning, Enrico; Günther, Julia; Merz, Jaqueline; Steinmüller, Frauke; Utpatel, Kirsten; Cigliano, Antonio; Peters, Kristin; Pilo, Maria G.; Evert, Matthias; Calvisi, Diego F.; Dombrowski, Frank

    2016-01-01

    Activation of the epidermal growth factor receptor (EGFR) signaling pathway promotes the development of hepatocellular adenoma (HCA) and carcinoma (HCC). The selective EGFR inhibitor Gefitinib was found to prevent hepatocarcinogenesis in rat cirrhotic livers. Thus, Gefitinib might reduce progression of pre-neoplastic liver lesions to HCC. In short- and long-term experiments, administration of N-Nitrosomorpholine (NNM) or intrahepatic transplantation of pancreatic islets in diabetic (PTx), thyroid follicles in thyroidectomized (TTx) and ovarian fragments in ovariectomized (OTx) rats was conducted for the induction of foci of altered hepatocytes (FAH). Gefitinib was administered for two weeks (20 mg/kg) or three and nine months (10 mg/kg). In NNM-treated rats, Gefitinib administration decreased the amount of FAH when compared to controls. The amount of HCA and HCC was decreased, but development was not prevented. Upon all transplantation models, proliferative activity of FAH was lower after administration of Gefitinib in short-term experiments. Nevertheless, the burden of HCA and HCC was not changed in later stages. Thus, EGFR inhibition by Gefitinib diminishes chemical and hormonal also induced hepatocarcinogenesis in the initiation stage in the non-cirrhotic liver. However, progression to malignant hepatocellular tumors was not prevented, indicating only a limited relevance of the EGFR signaling cascade in later stages of hepatocarcinogenesis. PMID:27669229

  12. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion: A case report in a patient with metastatic pancreatic adenocarcinoma.

    PubMed

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-06-01

    Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date.We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy.Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited.

  13. α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways.

    PubMed

    Ru, Yusha; Huang, Yue; Liu, Huijuan; Du, Juan; Meng, Zhu; Dou, Zexia; Liu, Xun; Wei, Rui Hua; Zhang, Yan; Zhao, Shaozhen

    2015-12-21

    Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability, and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-α, IL-1β, and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10(-4) μg/μl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH's protective effects, suggesting that both pathways are necessary for α-MSH's protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED.

  14. Extracts of Artocarpus communis decrease α-melanocyte stimulating hormone-induced melanogenesis through activation of ERK and JNK signaling pathways.

    PubMed

    Fu, Yi-Tzu; Lee, Chiang-Wen; Ko, Horng-Huey; Yen, Feng-Lin

    2014-01-01

    Artocarpus communis is an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts of A. communis have been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well as α-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract of A. communis (ACM) and various organic partition fractions of A. communis on melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics.

  15. Effects of interleukin-1 beta on the steroid-induced luteinizing hormone surge: role of norepinephrine in the medial preoptic area.

    PubMed

    MohanKumar, Sheba M J; MohanKumar, P S

    2002-08-15

    Interleukin-1beta (IL-1beta), a cytokine, is known to inhibit the preovulatory surge of luteinizing hormone (LH); however, the mechanism by which it does so is unclear. This study was done to see if this effect is mediated through hypothalamic catecholamines. Adult female Sprague-Dawley rats were ovariectomized and implanted with a push-pull cannula in the medial preoptic area (MPA) of the hypothalamus. They were injected subcutaneously with 30 microg of Estradiol on the day 8 after surgery and with 2mg of Progesterone on day 10 at 1000 h. On the day of perfusion (day 10), the rats were injected with IL-1beta or its vehicle at 1300 h. Perfusate samples from the MPA and blood samples from a jugular catheter were collected from 1300 to 1800 h. Catecholamine concentrations in the perfusate were measured using high performance liquid chromatography (HPLC)-EC and LH levels in the serum using RIA. Norepinephrine release in the MPA of control rats increased significantly at 1530, 1600, and 1630 h paralelling an increase in LH at 1600 h. In contrast, IL-1beta treatment blocked the LH surge and the rise in norepinephrine release in the MPA. No changes were observed in dopamine release, both in control and IL-treated animals. These results demonstrate for the first time that IL-induced suppression of the LH surge is probably mediated through inhibition of norepinephrine release in the MPA.

  16. Systemic overexpression of growth hormone (GH) in transgenic FVB/N inbred mice: an optimized model for holistic studies of molecular mechanisms underlying GH-induced kidney pathology.

    PubMed

    von Waldthausen, Dagmar C; Schneider, Marlon R; Renner-Müller, Ingrid; Rauleder, Dirk N; Herbach, Nadja; Aigner, Bernhard; Wanke, Rüdiger; Wolf, Eckhard

    2008-08-01

    Transgenic mice overexpressing growth hormone (GH) display a plethora of phenotypic alterations and provide unique models for studying and influencing consequences of chronic GH excess. Since the first report on GH transgenic mice was published in 1982, many different mouse models overexpressing GH from various species at different levels and with different tissue specificities were established, most of them on random-bred or hybrid genetic background. We have generated a new transgenic mouse model on FVB/N inbred background, expressing bovine (b) GH under the control of the chicken beta-actin promoter (cbetaa). cbetaa-bGH transgenic mice exhibit ubiquitous expression of bGH mRNA and protein and circulating bGH levels in the range of several microg/ml, resulting in markedly stimulated growth and the characteristic spectrum of pathological lesions which were described in previous GH overexpressing mouse models. Importantly, a consistent sequence of renal alterations is observed, mimicking progressive kidney disease in human patients. The novel, genetically standardized GH transgenic mouse model is ideal for holistic transcriptome and proteome studies aiming at the identification of the molecular mechanisms underlying GH-induced pathological alterations especially in the kidney. Moreover, genetically defined cbetaa-bGH mice facilitate random mutagenesis screens for modifier genes which influence the effects of chronic GH excess and associated pathological lesions.

  17. Growth hormone suppresses the expression of IGFBP-5, and promotes the IGF-I-induced phosphorylation of Akt in bovine mammary epithelial cells.

    PubMed

    Sakamoto, Kazuhito; Yano, Tomoki; Kobayashi, Takuya; Hagino, Akihiko; Aso, Hisashi; Obara, Yoshiaki

    2007-05-01

    Growth hormone (GH) plays a specific role to inhibit apoptosis in the bovine mammary gland through the insulin-like growth factor (IGF)-I system, however, the mechanism of GH action is poorly understood. In this study, we show that GH dramatically inhibits the expression of IGFBP-5, and GH along with IGF-I enhanced the phosphorylation of Akt through the reduction of IGF binding protein (IGFBP)-5. To determine how GH affects Akt through IGF-I in bovine mammary epithelial cells (BMECs), we examined the phosphorylation of Akt in GH treated BMECs and found that IGF-I induced phosphorylation of Akt was significantly enhanced by the treatment with GH. We demonstrated that GH reduces mRNA and protein expression of IGFBP-5 in BMECs, but it does not affect the expression of IGFBP-3. To determine that the enhanced effect of the Akt phosphorylation by the treatment of GH is due to the inhibition of the expression of IGFBP-5, we examined the effect of IGFBP-3 and -5 on the phosphorylation of Akt through IGF-I in the GH-treated BMECs. The phosphorylation of Akt was inhibited in a dose-dependent manner when IGFBP-5 was added at varying concentrations and was also inhibited in the presence of IGFBP-3. The results of this study suggest that GH plays an important role on mammary gland involution in bovine mammary epithelial cells.

  18. Thyroid Hormone-Induced Cytosol-to-Nuclear Translocation of Rat Liver Nrf2 Is Dependent on Kupffer Cell Functioning

    PubMed Central

    Videla, Luis A.; Cornejo, Pamela; Romanque, Pamela; Santibáñez, Catherine; Castillo, Iván; Vargas, Romina

    2012-01-01

    L-3,3′,5-triiodothyronine (T3) administration upregulates nuclear factor-E2-related factor 2 (Nrf2) in rat liver, which is redox-sensitive transcription factor mediating cytoprotection. In this work, we studied the role of Kupffer cell respiratory burst activity, a process related to reactive oxygen species generation and liver homeostasis, in Nrf2 activation using the macrophage inactivator gadolinium chloride (GdCl3; 10 mg/kg i.v. 72 h before T3 [0.1 mg/kg i.p.]) or NADPH oxidase inhibitor apocynin (1.5 mmol/L added to the drinking water for 7 days before T3), and determinations were performed 2 h after T3. T3 increased nuclear/cytosolic Nrf2 content ratio and levels of heme oxygenase 1 (HO-1), catalytic subunit of glutamate cysteine ligase, and thioredoxin (Western blot) over control values, proteins whose gene transcription is induced by Nrf2. These changes were suppressed by GdCl3 treatment prior to T3, an agent-eliciting Kupffer-cell depletion, inhibition of colloidal carbon phagocytosis, and the associated respiratory burst activity, with enhancement in nuclear inhibitor of Nrf2 kelch-like ECH-associated protein 1 (Keap1)/Nrf2 content ratios suggesting Nrf2 degradation. Under these conditions, T3-induced tumor necrosis factor-α (TNF-α) response was eliminated by previous GdCl3 administration. Similar to GdCl3, apocynin given before T3 significantly reduced liver Nrf2 activation and HO-1 expression, a NADPH oxidase inhibitor eliciting abolishment of colloidal carbon-induced respiratory burst activity without altering carbon phagocytosis. It is concluded that Kupffer cell functioning is essential for upregulation of liver Nrf2-signaling pathway by T3. This contention is supported by suppression of the respiratory burst activity of Kupffer cells and the associated reactive oxygen species production by GdCl3 or apocynin given prior to T3, thus hindering Nrf2 activation. PMID:22649286

  19. Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

    SciTech Connect

    Kim, Young C. Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

    2007-08-15

    Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards.

  20. Hormone-induced luteolysis on physiologically persisting corpora lutea in Eurasian and Iberian lynx (Lynx lynx and Lynx pardinus).

    PubMed

    Painer, Johanna; Goeritz, Frank; Dehnhard, Martin; Hildebrandt, Thomas B; Naidenko, Sergey V; Sánchez, Iñigo; Quevedo Muñoz, Miguel A; Jewgenow, Katarina

    2014-09-01

    The Iberian lynx (Lynx pardinus) is the most critically endangered felid. A high reproductive success within the Iberian Lynx Conservation Breeding Program is crucial to maintaining the goal of reintroducing captive born offspring to the wild and thus increasing the population. Lynx follow a unique reproductive strategy with a monoestrous cycle and persisting CLs over many years. These persistent CLs constantly produce progesterone (on average 5 ng/mL) and are hypothesized to hinder a polyestrous cyclicity in lynx. The aim of this study was to evaluate whether artificial luteolysis can be achieved with common luteolytic drugs and if luteolysis would induce a second estrus naturally. We observed a functional regression of lynx CLs after artificial luteolysis with 2.5 μg/kg body weight PGF2α analogue (cloprostenol) administered three times every 16 hours. We could see a similar effect when combining cloprostenol with other drugs like an anti-gestagen (aglepristone) or a dopamin-agonist (prolactin-inhibitor, cabergolin) or by prolonging the cloprostenol administration to a total of 5 days. However, the sample size was too small to draw conclusions about which protocol is superior or if combining different drugs would result in a positive synergism. Neither structural regression of CLs nor subsequent spontaneous estrus induction was induced with any of these treatments. We suggest that a dose of 2.5 μg/kg body weight cloprostenol administered once daily over 3 to 5 days is sufficient for functional luteolysis in lynx. The next step would be to compare the success of estrus induction with or without the preceding artificial luteolysis.

  1. Modulation of adrenocorticotrophin hormone (ACTH)-induced expression of stress-related genes by PUFA in inter-renal cells from European sea bass (Dicentrarchus labrax).

    PubMed

    Montero, Daniel; Terova, Genciana; Rimoldi, Simona; Tort, Lluis; Negrin, Davinia; Zamorano, María Jesús; Izquierdo, Marisol

    2015-01-01

    Dietary fatty acids have been shown to exert a clear effect on the stress response, modulating the release of cortisol. The role of fatty acids on the expression of steroidogenic genes has been described in mammals, but little is known in fish. The effect of different fatty acids on the release of cortisol and expression of stress-related genes of European sea bass (Dicentrarchus labrax) head kidney, induced by a pulse of adenocorticotrophin hormone (ACTH), was studied. Tissue was maintained in superfusion with 60 min of incubation with EPA, DHA, arachidonic acid (ARA), linoleic acid or α-linolenic acid (ALA) during 490 min. Cortisol was measured by RIA. The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real-time RT-PCR. There was an effect of the type of fatty acid on the ACTH-induced release of cortisol, values from ALA treatment being elevated within all of the experimental period. The expression of some steroidogenic genes, such as the steroidogenic acute regulatory protein (StAR) and c-fos, were affected by fatty acids, ALA increasing the expression of StAR after 1 h of ACTH stimulation whereas DHA, ARA and ALA increased the expression of c-fos after 20 min. ARA increased expression of the 11β-hydroxylase gene. Expression of heat shock protein 70 (HSP70) was increased in all the experimental treatments except for ARA. Results corroborate previous studies of the effect of different fatty acids on the release of cortisol in marine fish and demonstrate that those effects are mediated by alteration of the expression of steroidogenic genes.

  2. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.

    PubMed

    Martinez, Bridget; Soñanez-Organis, José G; Viscarra, Jose A; Jaques, John T; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

    2016-03-15

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition.

  3. Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model.

    PubMed

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients.

  4. Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model

    PubMed Central

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. To compare the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50–150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6–12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

  5. Fuel oil-induced adrenal hypertrophy in ranch mink (Mustela vison): effects of sex, fuel oil weathering, and response to adrenocorticotropic hormone.

    PubMed

    Mohr, F C; Lasley, B; Bursian, S

    2010-01-01

    Environmental contamination by petroleum hydrocarbons from anthropogenic sources can be a cause of stress for free-ranging wildlife. The response of wildlife to chemical contaminants requires that the hypothalamic-pituitary-adrenal (HPA) axis be precisely regulated to allow for proper glucocorticoid-mediated adaptive responses. Chronic oral exposure to low concentrations of bunker C fuel oil causes the development of adrenal hypertrophy in male ranch mink (Mustela vison) without increasing serum or fecal glucocorticoid concentrations. This hypertrophy is an adaptive response to fuel oil-induced adrenal insufficiency. To determine if the same phenomenon occurs in female mink or male mink exposed to artificially weathered fuel oil, female mink were fed 0 ppm (mineral oil) or 420 ppm fuel oil and male mink were exposed to 0 ppm, 420 ppm fuel oil, or 480 ppm artificially weathered fuel oil in the diet for 60-62 days. At the end of the exposure, serum glucocorticoid concentrations were assayed along with body and organ weight measurements. Fecal glucocorticoid concentrations were assayed at time points throughout the exposure. Male mink fed fuel oil or weathered fuel oil and female mink fed fuel oil had adrenal enlargement without any significant increases in the serum or fecal concentration of glucocorticoids, which is consistent with fuel oil-induced adrenal insufficiency. To address the physiological consequences of adrenal insufficiency, fuel oil-exposed male mink were administered an adrenocorticotropic hormone (ACTH) stimulation test. Fuel oil-exposed animals had a smaller incremental increase in serum glucocorticoid concentration after ACTH challenge compared to control animals. Our findings provide further evidence that the HPA axis of fuel oil-exposed animals is compromised and, therefore, not able to respond appropriately to the diverse stressors found in the environment.

  6. Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis

    PubMed Central

    2010-01-01

    Background Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis. Methods Female B10.Q-ncf1*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines. Results Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6. Conclusions This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA. PMID:21159208

  7. Effect of exercise intensity on weight changes and sexual hormones (androstenedione and free testosterone) in female rats with estradiol valerate-induced PCOS

    PubMed Central

    2014-01-01

    Introduction Weight gain and fat accumulation are predisposing factors of PCOS. Life-style modification, including increasing physical activity, is the first line approach in managing PCOS. The objective of this study is to assess the effect of exercise intensity on weight changes, androstenedione and free testosterone level in female rats with estradiol valerate induced PCOS. Method and materials 40 female Wistar rats were selected (180 ± 20 g). They had every 2 to 3 consecutive estrous cycles during 12 to 14 days. The study was approved by ethical committee of Jahrom University of Medical Sciences. The first two groups were divided into control (n = 10) and polycystic (n = 30) that were induced PCOS by estradiol valerate injection after 60 days. The polycystic groups were divided into three groups of sham (n = 10), experiment group with low-intensity exercise (pco + l.exe) (n = 10) and experiment group with moderate intensity exercise (pco + m.exe) (n = 10). Exercises were performed during 6 sessions of 60 minutes per week for 8 weeks. (Moderate intensity: 28 m/min-70%–75%VO2Max. Low intensity (20 m/min-50%–55%VO2Max) running at 0 slope, 1 h/day, 6 days/week). ANOVA and LSD test were used for data analysis. Results In the present study, no significant differences were found in the decrease of total weights of rats. And also androstenedione level changes in experiment groups were higher compared to control group but no significant differences were found, also free testosterone level was significantly higher than the observer group. Conclusion According to weight changes and sexual hormones (Free testosterone and androstenedione) exercise training especially with low intensity may improve symptoms of polycystic ovary syndrome. PMID:24708600

  8. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    SciTech Connect

    Al-Kafaji, Ghada; Malik, Afshan N.

    2010-01-22

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  9. Deciding about hormone therapy

    MedlinePlus

    HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding

  10. Enhancement of lindane-induced liver oxidative stress and hepatotoxicity by thyroid hormone is reduced by gadolinium chloride.

    PubMed

    Simon-Giavarotti, Karin A; Giavarotti, Leandro; Gomes, Ligia F; Lima, Alessandra F; Veridiano, Adriano M; Garcia, Eduardo A; Mora, Oswaldo A; Fernández, Virginia; Videla, Luis A; Junqueira, Virginia B C

    2002-10-01

    The role of Kupffer cells in the hepatocellular injury and oxidative stress induced by lindane (20 mg/kg; 24h) in hyperthyroid rats (daily doses of 0.1 mg L-3,3',5-triiodothyronine (T3)/kg for three consecutive days) was assessed by the simultaneous administration of gadolinium chloride (GdCl3; 2 doses of 10mg/kg on alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver microsomal superoxide radical (O2.-) production and NADPH cytochrome c reductase activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and catalase activity, and glutathione (GSH) content over control values. These changes are paralleled by a substantial increase in the lipid peroxidation potential of the liver and in the O2.- generation/ SOD activity ratio, thus evidencing a higher oxidative stress status that correlates with the development of liver injury characterized by neutrophil infiltration and necrosis. Kupffer cell inactivation by GdCl3 suppresses liver injury in lindane/T3-treated rats with normalization of altered oxidative stress-related parameters, excepting the reduction in the content of GSH and in catalase activity. It is concluded that lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in the oxidative stress status of the liver, is largely dependent on Kupffer cell function, which may involve generation of mediators leading to pro-oxidant and inflammatory processes.

  11. Possible involvement of stress hormones and hyperglycaemia in chronic mild stress-induced impairment of immune functions in diabetic mice.

    PubMed

    Rubinstein, M R; Cremaschi, G A; Oliveri, L M; Gerez, E N; Wald, M R; Genaro, A M

    2010-09-01

    Stress, an important aspect of modern life, has long been associated with an altered homeostatic state. Little is known about the effect of the life stress on the outcome of diabetes mellitus, especially related to the higher risk of infections. Here, we evaluate the effects of chronic mild stress (CMS) exposure on the evolution of type I diabetes induced by streptozotocin administration in BALB/c mice. Exposure of diabetic mice to CMS resulted in a significant reduction of survival and a sustained increase in blood glucose values. Concerning the immune response, chronic stress had a differential effect in mice with diabetes with respect to controls, showing a marked decrease in both T- and B-cell proliferation. No correlation was found between splenic catecholamine or circulating corticosterone levels and the proliferative response. However, a significant negative correlation was found between glucose levels and concanavalin A- and lipopolysaccharide-stimulated proliferative responses of T and B cells. A positive correlation between blood glucose and splenic catecholamine concentrations was found in diabetic mice but not in controls subjected to CMS. Hence, the present report shows that diabetic mice show a worse performance in immune function after stress exposure, pointing to the importance of considering life stress as a risk factor for patients with diabetes.

  12. Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues.

    PubMed

    Hood, A; Klaassen, C D

    2000-03-15

    Microsomal enzyme inducers, such as phenobarbital (PB), pregnenolone-16alpha-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are more effective at reducing serum thyroxine (T(4)) than serum triiodothyronine (T(3)). It is possible that rats treated with PB and PCN maintain serum T(3) by increasing serum TSH, which stimulates the thyroid gland to synthesize more T(3). However, it is unclear how serum T(3) is maintained in rats treated with 3MC or PCB, because serum TSH is not increased in these rats. We hypothesized that increased conversion of T(4) to T(3), catalyzed by outer-ring deiodinases (ORD) type-I and -II, is the reason serum T(3) is maintained in rats treated with 3MC or PCB. Furthermore, 3MC and PCB do not increase serum TSH, whereas PB and PCN do, because type-II ORD activity in the pituitary of 3MC- and PCB-treated rats is increased greater than in rats treated with PB or PCN. To test these two hypotheses, male Sprague-Dawley rats were fed either a basal diet or a diet containing PB (300, 600, 1200, or 2400 ppm), PCN (200, 400, 800, or 1600 ppm), 3MC (50, 100, 200, or 400 ppm), or PCB (25, 50, 100, or 200 ppm) for 7 days. Type-I ORD activity was measured in thyroid, kidney, and liver, whereas type-II ORD activity was measured in brown adipose tissue, pituitary, and brain. Type-I ORD activity in thyroid was not affected by PB, 3MC, or PCB treatments, and was slightly increased by PCN. Type-I ORD activity in kidney was not affected by PB, PCN, or 3MC treatments, and was reduced by PCB treatment. Type-I ORD activity in liver was reduced by PB, PCN, 3MC, and PCB treatments. Type-II ORD activity in brown adipose tissue was unaffected by any of the four treatments. Type-II ORD activity in pituitary was unaffected by PB or 3MC treatments, and was increased by PCN or PCB treatments. Type-II ORD activity in brain was unaffected by PB treatment, and was increased by PCN, 3MC, and PCB treatments. Overall, total ORD activity, calculated by

  13. Central lipoprivation-induced suppression of luteinizing hormone pulses is mediated by paraventricular catecholaminergic inputs in female rats.

    PubMed

    Sajapitak, Somchai; Iwata, Kinuyo; Shahab, Mohammad; Uenoyama, Yoshihisa; Yamada, Shunji; Kinoshita, Mika; Bari, Farida Y; I'Anson, Helen; Tsukamura, Hiroko; Maeda, Kei-ichiro

    2008-06-01

    The present study aims to clarify the role of fatty acids in regulating pulsatile LH secretion in rats. To produce an acute central lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acids oxidation, was administered into the fourth cerebroventricle (4V) in ad libitum fed ovariectomized (OVX) rats (0.4, 2, and 10 micromol/rat) with or without an estradiol (E2) implant producing diestrus plasma E2 levels. Pulsatile LH secretion was suppressed by 4V MA administration in a dose-dependent manner in both OVX and OVX plus E2 rats. Mean LH levels and LH pulse frequency and amplitude were significantly reduced by the highest dose of MA in OVX rats, and by the middle and highest dose of MA in E2-treated rats, suggesting that estrogen enhanced LH suppression. Blood glucose levels increased immediately after the highest dose of MA in both groups. Fourth ventricular injection of trimetazidine (2 and 3 micromol/rat), another inhibitor of fatty acids oxidation, also inhibited pulsatile LH release, resulting in significant and dose-dependent suppression of LH pulse frequency and an increase in blood glucose levels in OVX plus E2 rats. In contrast, peripheral injection of the highest 4V dose of MA (10 micromol/rat) did not alter LH release or blood glucose levels. Microdialysis of the hypothalamic paraventricular nucleus (PVN) revealed that norepinephrine release in the region was increased by 4V MA administration. Preinjection of alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, into the PVN completely blocked the lipoprivic inhibition of LH and the counter-regulatory increase in blood glucose levels in OVX plus E2 rats. Together, these studies indicate that fatty acid availability may be sensed by a central detector, located in the lower brainstem to maintain reproduction, and that noradrenergic inputs to the PVN mediate this lipoprivic-induced suppression of LH release.

  14. [Hormonal dysnatremia].

    PubMed

    Karaca, P; Desailloud, R

    2013-10-01

    Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.

  15. Gamete ripening and hormonal correlates in three strains of lake trout

    USGS Publications Warehouse

    Foster, N.R.; O'Connor, D.V.; Schreck, C.B.

    1993-01-01

    In our 2-year laboratory study of hatchery-reared adult lake trout Salvelinus namaycush of the Seneca Lake, Marquette (Lake Superior Lean), and Jenny Lake strains, we compared gamete ripening times and changes in plasma concentrations of seven hormones. If interstrain differences in these traits were found, such differences might help explain the apparent failure of stocked fish of these strains to develop large, naturally reproducing populations in the Great Lakes. The complex temporal changes in plasma hormone levels that occur during sexual maturation in lake trout have not been previously described. We detected little evidence of temporal isolation that would prevent interbreeding among the three strains. Strain had no effect on ovulation date (OD) in either year. Strain did not affect spermiation onset date (SOD) in year 1 but did in year 2, when the mean SOD of Jenny Lake males was earlier than that of Seneca Lake males but not different from that of Marquette males. Hormonal data were normalized around ODs for individual females and SODs for individual males. In females, estradiol-17β (E2) was highest 8 weeks before the OD; the highest testosterone (T) level occurred 6 weeks before the OD, and the next highest level occurred simultaneously with the highest level of 11-ketotestosterone (11-KT) 2 weeks before the OD. Plasma levels of 17∝-hydroxy-20β-dihydroprogesterone (DHP) peaked 1 week before the OD, then abruptly declined immediately after. Cortisol (F), triiodothyronine (T3), and thyroxine (T4) were highly variable, but F was the only hormone that showed no trend with week in either year. In males, plasma E2 levels were highest 3 weeks before the SOD, highest levels of T and of 11-KT occurred simultaneously 2 weeks after the SOD, and DHP peaked 5 weeks after the SOD and 3 weeks after the highest levels of T and 11-KT. As in females, plasma levels of F, T3, and T4 were highly variable, and F was the only hormone that showed no trend with week in

  16. Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    Osteoblasts respond to both fluid shear and parathyroid hormone (PTH) with a rapid increase in intracellular calcium concentration ([Ca2+]i). Because both stimuli modulate the kinetics of the mechanosensitive cation channel (MSCC), we postulated PTH would enhance the [Ca2+]i response to fluid shear by increasing the sensitivity of MSCCs. After a 3-minute preflow at 1 dyne/cm2, MC3T3-E1 cells were subjected to various levels of shear and changes in [Ca2+]i were assessed using Fura-2. Pretreatment with 50 nM bovine PTH(1-34) [bPTH(1-34)] significantly enhanced the shear magnitude-dependent increase in [Ca2+]i. Gadolinium (Gd3+), an MSCC blocker, significantly inhibited the mean peak [Ca2+]i response to shear and shear + bPTH(1-34). Nifedipine (Nif), an L-type voltage-sensitive Ca2+ channel (VSCC) blocker, also significantly reduced the [Ca2+]i response to shear + bPTH(1-34), but not to shear alone, suggesting VSCC activation plays an interactive role in the action of these stimuli together. Activation of either the protein kinase C (PKC) or protein kinase A (PKA) pathways with specific agonists indicated that PKC activation did not alter the Ca2+ response to shear, whereas PKA activation significantly increased the [Ca2+]i response to lower magnitudes of shear. bPTH(1-34), which activates both pathways, induced the greatest [Ca2+]i response at each level of shear, suggesting an interaction of these pathways in this response. These data indicate that PTH significantly enhances the [Ca2+]i response to shear primarily via PKA modulation of the MSCC and VSCC.

  17. A novel and selective melanin-concentrating hormone receptor 1 antagonist ameliorates obesity and hepatic steatosis in diet-induced obese rodent models.

    PubMed

    Kawata, Yayoi; Okuda, Shoki; Hotta, Natsu; Igawa, Hideyuki; Takahashi, Masashi; Ikoma, Minoru; Kasai, Shizuo; Ando, Ayumi; Satomi, Yoshinori; Nishida, Mayumi; Nakayama, Masaharu; Yamamoto, Syunsuke; Nagisa, Yasutaka; Takekawa, Shiro

    2017-02-05

    Melanin-concentrating hormone (MCH), a cyclic neuropeptide expressed predominantly in the lateral hypothalamus, plays an important role in the control of feeding behavior and energy homeostasis. Mice lacking MCH or MCH1 receptor are resistant to diet-induced obesity (DIO) and MCH1 receptor antagonists show potent anti-obesity effects in preclinical studies, indicating that MCH1 receptor is a promising target for anti-obesity drugs. Moreover, recent studies have suggested the potential of MCH1 receptor antagonists for treatment of non-alcoholic fatty liver disease (NAFLD). In the present study, we show the anti-obesity and anti-hepatosteatosis effect of our novel MCH1 receptor antagonist, Compound A. Repeated oral administration of Compound A resulted in dose-dependent body weight reduction and had an anorectic effect in DIO mice. The body weight lowering effect of Compound A was more potent than that of pair-feeding. Compound A also reduced lipid content and the expression level of lipogenesis-, inflammation-, and fibrosis-related genes in the liver of DIO mice. Conversely, intracerebroventricular infusion of MCH caused induction of hepatic steatosis as well as increase in body weight in high-fat diet-fed wild type mice, but not MCH1 receptor knockout mice. The pair-feeding study revealed the MCH-MCH1 receptor system affects hepatic steatosis through a mechanism that is independent of body weight change. Metabolome analysis demonstrated that Compound A upregulated lipid metabolism-related molecules, such as acylcarnitines and cardiolipins, in the liver. These findings suggest that our novel MCH1 receptor antagonist, Compound A, exerts its beneficial therapeutic effect on NAFLD and obesity through a central MCH-MCH1 receptor pathway.

  18. Early-life stress-induced anxiety-related behavior in adult mice partially requires forebrain corticotropin-releasing hormone receptor 1.

    PubMed

    Wang, Xiao-Dong; Labermaier, Christiana; Holsboer, Florian; Wurst, Wolfgang; Deussing, Jan M; Müller, Marianne B; Schmidt, Mathias V

    2012-08-01

    Early-life stress may lead to persistent changes in central corticotropin-releasing hormone (CRH) and the CRH receptor 1 (CRHR1) system that modulates anxiety-related behavior. However, it remains unknown whether CRH-CRHR1 signaling is involved in early-life stress-induced anxiety-related behavior in adult animals. In the present study, we used conditional forebrain CRHR1 knockout (CRHR1-CKO) mice and examined the potential role of forebrain CRHR1 in the anxiogenic effects of early-life stress. As adults, wild-type mice that received unstable maternal care during the first postnatal week showed reduced body weight gain and increased anxiety levels in the open field test, which were prevented in stressed CRHR1-CKO mice. In the light-dark box test, control CRHR1-CKO mice were less anxious, but early-life stress increased anxiety levels in both wild-type and CRHR1-CKO mice. In the elevated plus maze test, early-life stress had only subtle effects on anxiety-related behavior. Moreover, early-life stress did not alter the basal home cage activity and gene expression levels of key hypothalamic-pituitary-adrenal axis regulators in adult wild-type and CRHR1-CKO mice, but enhanced neuroendocrine reactivity to acute immobilization stress in CRHR1-CKO mice. Our findings highlight the importance of forebrain CRHR1 in modulating some of the anxiogenic effects of early-life stress, and suggest that other neural circuits are also involved in the programming effects of early-life stress on anxiety-related behavior.

  19. Betulin binds to melanocortin receptors and antagonizes alpha-melanocyte stimulating hormone induced cAMP generation in mouse melanoma cells.

    PubMed

    Muceniece, Ruta; Saleniece, Kristine; Riekstina, Una; Krigere, Liga; Tirzitis, Gunars; Ancans, Janis

    2007-01-01

    Betulin is a principal component of birch bark and is known to possess a broad range of biological activities, including antiinflammatory, antiviral and anticancer actions. The present study was carried out in vitro to clarify the influence of betulin on melanocortin (MC) receptor-ergic signalling by using COS-7 cells transfected with corresponding human MC receptor DNA. The results showed that betulin binds to the human melanocortin MC1, three to five receptors with selectivity to the MC1 subtype (K(i) value 1.022 +/- 0.115 microM). Betulin binds to the MC receptors with the following potency order-MC > MC3 > MC5 > MC4. Betulin itself does not stimulate cAMP generation, however, it slightly antagonizes alpha-melanocyte-stimulating hormone (alpha-MSH)-induced cAMP accumulation in the mouse melanoma cell line B16-F1. As a water-insoluble substance, betulin was dissolved in DMSO therefore DMSO competition with the labelled ligand NDP-MSH for the binding to the MC receptors was tested in the identical experimental set-up. We found that DMSO competes for binding to all the MC receptor subtypes, at 20% concentration and above. Selectivity for one or another receptor subtype was not observed. We have demonstrated for the first time, the ability of the plant compound betulin to bind to the MC receptors. One may suggest MC receptor MC1 subtype as the essential target for the antimelanoma action of betulin and its structurally close molecules such as betulinic acid. Moreover, we have found a new non-peptide small molecule MC mimetic, that is betulin. Thus, we report a new chemical motif for the binding to the MC receptors that could be used as a template for the search of more selective MC mimetics.

  20. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    SciTech Connect

    Deusing, Dorothé Jenni Beyrer, Melanie Fitzenberger, Elena Wenzel, Uwe

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

  1. Anti-tumor necrosis factor agent PEG-sTNFRI improves the growth hormone/insulin-like growth factor-I system in adjuvant-induced arthritic rats.

    PubMed

    Granado, Miriam; Priego, Teresa; Martín, Ana Isabel; Vara, Elena; López-Calderón, Asunción; Angeles Villanúa, María

    2006-04-24

    Adjuvant-induced arthritis is associated with body weight loss and decreased pituitary growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I) synthesis. Cytokines as tumor necrosis factor (TNF) mediate wasting associated with chronic inflammation. The aim of this study was to analyse whether the inhibition of TNF is able to revert the decrease in the body weight and the GH/IGF-I axis in arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with polyethylene glycol linked to soluble TNF receptor p55 (PEG-sTNFRI) (1 mg/kg, s.c.) or saline for 8 days. There was a significant decrease in pituitary GH mRNA (P<0.05), hepatic IGF-I mRNA (P<0.01) and serum concentrations of IGF-I (P<0.01) in arthritic rats. The 8-day administration of PEG-sTNFRI resulted in an increase in food intake (P<0.05) and body weight gain (P<0.01) in arthritic but not in control rats. There was an increase in pituitary GH mRNA after PEG-sTNFRI treatment both in control and in arthritic rats. There was a significant increase in IGF-I serum concentrations (P<0.05) and hepatic IGF-I mRNA expression (P<0.05) in control rats treated with PEG-sTNFRI, whereas the effect of this anti-TNF agent in arthritic rats was only statistically significant in hepatic IGF-I mRNA expression (P<0.05). These data suggest that TNF seems to be involved in the decrease in GH and IGF-I synthesis in arthritic rats.

  2. Suppression of episodic growth hormone secretion in streptozotocin-induced diabetic mice: time-course studies on the hypothalamic pituitary axis.

    PubMed

    Murao, S; Sato, M; Tamaki, M; Niimi, M; Ishida, T; Takahara, J

    1995-10-01

    To elucidate the roles of the hypothalamic peptides, GH-releasing hormone (GRH) and somatostatin (SRIH), potentially responsible for altered GH dynamics in diabetes, we studied the time courses of their changes in level associated with altered GH secretion in streptozotocin (STZ)-induced diabetic mice. Diabetic mice were used at 4, 7, and 14 days after STZ injection for analyses of 1) GH secretion in vivo, 2) hypothalamic GRH and SRIH messenger RNA (mRNA) levels, 3) pituitary GH mRNA and protein contents, and 4) pituitary GH response to GRH in vitro. GH secretion was completely suppressed 7 and 14 days after STZ injection. The hypothalamic GRH mRNA level was reduced to 59.8%, 61.2%, and 48.5% of control values at 4, 7, and 14 days, respectively. In contrast, the hypothalamic SRIH mRNA level was not altered at all of these time points. Pituitary GH mRNA and protein contents were significantly reduced to 70.2% and 61.5% of those in controls, respectively, only at 14 days. Pituitary GH responses to GRH at three doses (10, 50, and 250 nM) in vitro were remarkably increased at 4, 7, and 14 days. These findings indicate that the diabetic state rapidly and primarily inhibits hypothalamic GRH gene expression without affecting SRIH. A persistent decrease in hypothalamic GRH tone has been suggested to result in inhibition of GH synthesis in the pituitary. Enhancement of GH responsiveness to GRH may be due to the up-regulation of GRH receptors in the pituitary.

  3. The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice.

    PubMed

    Gohin, S; Carriero, A; Chenu, C; Pitsillides, A A; Arnett, T R; Marenzana, M

    2016-03-01

    There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 µg/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH-stimulated increase in cortical bone formation but had no clear-cut effects in trabecular bone. Co-treatment with L-NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO-mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone.

  4. Dehydration-induced endodormancy in crown buds of leafy spurge highlights involvement of MAF3- and RVE1-like homologs, and hormone signaling cross-talk.

    PubMed

    Doğramacı, Münevver; Horvath, David P; Anderson, James V

    2014-11-01

    Vegetative shoot growth from underground adventitious buds of leafy spurge is critical for survival of this invasive perennial weed after episodes of severe abiotic stress. To determine the impact that dehydration-stress has on molecular mechanisms associated with vegetative reproduction of leafy spurge, greenhouse plants were exposed to mild- (3-day), intermediate- (7-day), severe- (14-day) and extended- (21-day) dehydration treatments. Aerial tissues of treated plants were then decapitated and soil was rehydrated to determine the growth potential of underground adventitious buds. Compared to well-watered plants, mild-dehydration accelerated new vegetative shoot growth, whereas intermediate- through extended-dehydration treatments both delayed and reduced shoot growth. Results of vegetative regrowth further confirmed that 14 days of dehydration induced a full-state of endodormancy in crown buds, which was correlated with a significant (P < 0.05) change in abundance of 2,124 transcripts. Sub-network enrichment analyses of transcriptome data obtained from the various levels of dehydration treatment also identified central hubs of over-represented genes involved in processes such as hormone signaling (i.e., ABA, auxin, ethylene, GA, and JA), response to abiotic stress (DREB1A/2A, RD22) and light (PIF3), phosphorylation (MPK4/6), circadian regulation (CRY2, PHYA), and flowering (AGL20, AP2, FLC). Further, results from this and previous studies highlight homologs most similar to Arabidopsis HY5, MAF3, RVE1 and RD22 as potential molecular markers for endodormancy in crown buds of leafy spurge. Early response to mild dehydration also highlighted involvement of upstream ethylene and JA-signaling, whereas severe dehydration impacted ABA-signaling. The identification of conserved ABRE- and MYC-consensus, cis-acting elements in the promoter of leafy spurge genomic clones similar to Arabidopsis RVE1 (AT5G17300) implicates a potential role for ABA-signaling in its dehydration-induced

  5. Chronic estradiol-17β exposure suppresses hypothalamic norepinephrine release and the steroid-induced luteinizing hormone surge: Role of nitration of tyrosine hydroxylase

    PubMed Central

    Kasturi, Badrinarayanan S.; Mohan Kumar, Sheba M.J.; Sirivelu, Madhu P.; Shin, Andrew C.; Kumar, P.S. Mohan

    2012-01-01

    Chronic exposure to estrogens is known to produce a variety of deleterious effects in women including breast and ovarian cancer and anovulation. In female rats, exposure to low levels of estradiol-17β (E2) decreases hypothalamic norepinephrine (NE) to suppress luteinizing hormone (LH) secretion and cause failure of ovulation. We hypothesized that E2 exposure most likely decreases NE release in the medial preoptic area (MPA) of the hypothalamus to produce this effect and that this may be due to E2- induced inflammatory changes in noradrenergic nuclei leading to nitration of an enzyme involved in NE synthesis. To test this, female Sprague Dawley rats were sham implanted or implanted with slow release E2 pellets (20 ng/day) for 30, 60 or 90 days (E30, E60 and E90 respectively). At the end of the treatment period, the rats were implanted with a push-pull cannula in the MPA, ovariectomized and subjected to steroid priming to induce a LH surge. Perfusates were analyzed for NE levels using HPLC-EC. Blood samples collected simultaneously were analyzed for LH levels. We measured interleukin-1β (IL-1 β) and nitrate levels in brainstem noradrenergic nuclei that innervate the MPA. In control animals, there was a marked increase in NE levels in response to steroid priming at 1600h that was reduced in the E30 group, and completely abolished after 60 and 90 days of E2 exposure. LH profiles were similar to NE release profiles in control and E2-treated animals. We found that IL-1β levels increased in all three (A1, A2 and A6) noradrenergic nuclei with chronic E2 exposure, while nitrate levels increased only in the A6 region. There was an increase in the nitration of the NE synthesizing enzyme in the MPA in this group as well probably contributing to reduced NE synthesis. This could be a possible mechanism by which chronic E2 exposure decreases NE levels in the MPA to suppress the LH surge. PMID:23194835

  6. Original Research: Atorvastatin prevents rat cardiomyocyte hypertrophy induced by parathyroid hormone 1-34 associated with the Ras-ERK signaling.

    PubMed

    Liu, Xiaogang; Zou, Chunbo; Yu, Chengyuan; Xie, Rujuan; Sui, Manshu; Mu, Suhong; Li, Li; Zhao, Shilei

    2016-10-01

    We investigated the effects of atorvastatin (Ator) on cardiomyocyte hypertrophy (CMH) induced by rat parathyroid hormone 1-34 (PTH1-34) and Ras-extracellular signal regulated protein kinases 1/2 (ERK1/2) signaling. Rat cardiomyocytes were randomly divided into seven groups: normal controls (NC), PTH1-34 (10(-7) mol/L), Ator (10(-5) mol/L), farnesyl transferase inhibitors-276 (FTI-276, 4 × 10(-5) mol/L), PTH1-34 + Ator, PTH1-34 + FTI-276 and PTH1-34 + Ator + mevalonic acid (MVA, 10(-4) mol/L). After treatment, the hypertrophic responses of cardiomyocytes were assessed by measuring cell diameter, detecting protein synthesis, and single-cell protein content. The concentrations of hypertrophic markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured by ELISA. Protein expressions of ERK1/2, p-ERK1/2 and Ras were detected by western blotting. The results showed that compared with the PTH1-34 group, cellular diameter, 3H-leucine incorporation, single-cell protein content, ANP and BNP concentration decreased by 12.07 µm, 1622 cpm/well, 84.34 pg, 7.13 ng/L and 20.04 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were downregulated in PTH1-34 + Ator group (P < 0.05). Compared to the PTH1-34 + Ator group, the corresponding hypertrophic responses and hypertrophic markers increased by 4.95 µm, 750 cpm/well, 49.08 pg, 3.12 ng/L and 9.35 µg/L, respectively, and the expressions of Ras and p-ERK1/2 were upregulated in the PTH1-34 + Ator + MVA group (P < 0.05). In conclusion, Ator prevents neonatal rat CMH induced by PTH1-34 and Ras-ERK signaling may be involved in this process.

  7. Disruption of thyroid hormone homeostasis in Ugt1a-deficient Gunn rats by microsomal enzyme inducers is not due to enhanced thyroxine glucuronidation

    SciTech Connect

    Richardson, Terrilyn A.; Klaassen, Curtis D.

    2010-10-01

    Microsomal enzyme inducers (MEI) that increase UDP-glucuronosyltransferases (UGTs) are thought to increase glucuronidation of thyroxine (T{sub 4}), thus reducing serum T{sub 4}, and subsequently increasing thyroid stimulating hormone (TSH). Ugt1a1 and Ugt1a6 mediate T{sub 4} glucuronidation. Therefore, this experiment determined the involvement of Ugt1a enzymes in increased T{sub 4} glucuronidation, decreased serum T{sub 4}, and increased TSH after MEI treatment. Male Wistar and Ugt1a-deficient Wistar (Gunn) rats were fed a control diet or diet containing pregnenolone-16{alpha}-carbonitrile (PCN; 800 ppm), 3-methylcholanthrene (3-MC; 200 ppm), or Aroclor 1254 (PCB; 100 ppm) for 7 days. Serum T{sub 4}, triiodothyronine (T{sub 3}), and TSH concentrations, hepatic T{sub 4}/T{sub 3} glucuronidation, and thyroid histology and follicular cell proliferation were investigated. PCN, 3-MC, and PCB treatments decreased serum T{sub 4}, whereas serum T{sub 3} was maintained in both Gunn and Wistar rats (except for PCB treatment). TSH was increased in Wistar and Gunn rats after PCN (130 and 277%) or PCB treatment (72 and 60%). T{sub 4} glucuronidation in Wistar rats was increased after PCN (298%), 3-MC (85%), and PCB (450%), but was extremely low in Gunn rats, and unchanged after MEI. T{sub 3} glucuronidation was increased after PCN (121%) or PCB (58%) in Wistar rats, but only PCN increased T{sub 3} glucuronidation in Gunn rats (43%). PCN treatment induced thyroid morphological changes and increased follicular cell proliferation in both strains. These data demonstrate that T{sub 4} glucuronidation cannot be increased in Ugt1a-deficient Gunn rats. Thus, the decrease in serum T{sub 4}, increase in TSH, and increase in thyroid cell proliferation after MEI are not dependent on increased T{sub 4} glucuronidation, and cannot be attributed to Ugt1a enzymes.

  8. Hormone therapy in acne.

    PubMed

    Lakshmi, Chembolli

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  9. Thyroid Hormone Deiodinases and Cancer

    PubMed Central

    Casula, Sabina; Bianco, Antonio C.

    2012-01-01

    Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches. PMID:22675319

  10. Transcriptomics of shading-induced and NAA-induced abscission in apple (Malus domestica) reveals a shared pathway involving reduced photosynthesis, alterations in carbohydrate transport and signaling and hormone crosstalk

    PubMed Central

    2011-01-01

    Background Naphthaleneacetic acid (NAA), a synthetic auxin analogue, is widely used as an effective thinner in apple orchards. When applied shortly after fruit set, some fruit abscise leading to improved fruit size and quality. However, the thinning results of NAA are inconsistent and difficult to predict, sometimes leading to excess fruit drop or insufficient thinning which are costly to growers. This unpredictability reflects our incomplete understanding of the mode of action of NAA in promoting fruit abscission. Results Here we compared NAA-induced fruit drop with that caused by shading via gene expression profiling performed on the fruit abscission zone (FAZ), sampled 1, 3, and 5 d after treatment. More than 700 genes with significant changes in transcript abundance were identified from NAA-treated FAZ. Combining results from both treatments, we found that genes associated with photosynthesis, cell cycle and membrane/cellular trafficking were downregulated. On the other hand, there was up-regulation of genes related to ABA, ethylene biosynthesis and signaling, cell wall degradation and programmed cell death. While the differentially expressed gene sets for NAA and shading treatments shared only 25% identity, NAA and shading showed substantial similarity with respect to the classes of genes identified. Specifically, photosynthesis, carbon utilization, ABA and ethylene pathways were affected in both NAA- and shading-induced young fruit abscission. Moreover, we found that NAA, similar to shading, directly interfered with leaf photosynthesis by repressing photosystem II (PSII) efficiency within 10 minutes of treatment, suggesting that NAA and shading induced some of the same early responses due to reduced photosynthesis, which concurred with changes in hormone signaling pathways and triggered fruit abscission. Conclusions This study provides an extensive transcriptome study and a good platform for further investigation of possible regulatory genes involved in the

  11. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

    PubMed Central

    de Melo, T.S.; Lima, P.R.; Carvalho, K.M.M.B.; Fontenele, T.M.; Solon, F.R.N.; Tomé, A.R.; de Lemos, T.L.G.; da Cruz Fonseca, S.G.; Santos, F.A.; Rao, V.S.; de Queiroz, M.G.R.

    2017-01-01

    Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses. PMID:28076453

  12. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity.

    PubMed

    de Melo, T S; Lima, P R; Carvalho, K M M B; Fontenele, T M; Solon, F R N; Tomé, A R; de Lemos, T L G; da Cruz Fonseca, S G; Santos, F A; Rao, V S; de Queiroz, M G R

    2017-01-05

    Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

  13. Thyroid and glucocorticoid hormones induce expression of lactase-phlorizin hydrolase gene in CDX-2/HNF-1α co-transfected IEC-6 cells.

    PubMed

    Suzuki, Takuji; Mochizuki, Kazuki; Goda, Toshinao

    2014-01-01

    Thyroid and glucocorticoid hormones and several transcriptional factors such as caudal type homeobox (CDX)-2 and hepatocyte nuclear factor (HNF)-1α are important for the differentiation of small intestinal absorptive cells and the consequent expression of genes related to the digestion/absorption of carbohydrates. In this study, we investigated whether thyroid and glucocorticoid hormones enhanced the expression of lactase-phlorizin hydrolase (LPH) gene, an intestine-specific gene that encodes an enzyme for lactose digestion, in small intestinal stem-like IEC-6 cells co-transfected with CDX-2 and HNF-1α using a retrovirus system. Changes in expression of intestine-specific genes caused by treatment with thyroid and/or glucocorticoid hormones were monitored in empty vector-transfected cells and in CDX-2/HNF-1α co-transfected cells by qRT-PCR. Stable co-transfection with CDX-2 and HNF-1α evoked the expression of the LPH gene in IEC-6 cells. Furthermore, treatment with a thyroid hormone, triiodothyronine, and a glucocorticoid receptor agonist, dexamethasone, significantly enhanced expression of the LPH, CDX-2 and HNF-1α genes in CDX-2/HNF-1α co-transfected IEC-6 cells. These results suggest that thyroid and glucocorticoid hormones synergistically enhance expression of the LPH gene in CDX-2/HNF-1α co-transfected IEC-6 cells.