Ageing does not influence the ultrashort feedback control of GnRH secretion in vitro

1990 ◽  
Vol 122 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Elio Messi ◽  
Mariarosa Zanisi ◽  
Luciano Martini
Keyword(s):  
Feedback Control ◽  
Experimental Period ◽  
Feedback Mechanism ◽  
Male Rats ◽  
Male Rat ◽  
Gnrh Analogue ◽  
Feedback Systems ◽  
Gnrh Secretion ◽  
Gnrh Release

Abstract. Evidence indicates that long and short feedback systems are altered in the aged male rat. Data also indicate the existence of an ultrashort feedback mechanism controlling GnRH secretion. The present experiments were performed to test whether the ultrashort feedback control of GnRH is operating also in old male rats. Mediobasal hypothalami of 18-month-old male rats were perifused in vitro either in the presence or in the absence of a GnRH agonistic analogue (Buserelin: [D-Ser(TBU)6, Des-Gly10]GnRH ethylamide) and stimulated with 5-min pulses of K+ (for a total of six pulses) in order to test their ability to release GnRH. The hypothalamic fragment was exposed to the GnRH analogue either for a part of the experimental period (at the beginning or at the end) or for the whole duration of the perifusion. In both cases, the presence of the analogue diminished or totally abolished the responses to K+ stimulation. This is in line with the results obtained in young animals. The data suggest that the ultrashort feedback mechanism controlling GnRH release is normally functioning also in aged male rats despite the fact that other types of feedback mechanisms (long and short loop) are substantially altered.

scholarly journals Activin-A stimulates hypothalamic gonadotropin-releasing hormone release by the explanted male rat hypothalamus: interaction with inhibin and androgens

1998 ◽  
Vol 156 (2) ◽  
pp. 269-274 ◽  
Author(s):  
AE Calogero ◽  
N Burrello ◽  
AM Ossino ◽  
P Polosa ◽  
R D'Agata
Keyword(s):  
Activin A ◽  
Gonadotropin Releasing Hormone ◽  
Male Rats ◽  
Male Rat ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Releasing Hormone ◽  
Gnrh Release ◽  
Release In Vitro

The presence of activins in those hypothalamic regions containing gonadotropin-releasing hormone (GnRH)-secreting neurons suggests that these peptides may regulate the reproductive function modulating not only pituitary FSH release and biosynthesis, but also hypothalamic GnRH release. The purpose of this study was to evaluate the effects of activin-A, a homodimer of inhibin beta A subunit, on hypothalamic GnRH release in vitro and, because of their well known antithetical effects, to evaluate its interaction with inhibin. In addition, since androgens modulate the release of GnRH from male rat hypothalami, we thought it of interest to study the possible interplay between these steroids and activin on GnRH release. To accomplish this, we employed a hypothalamic organ culture system which enabled us to evaluate GnRH release from individually incubated hemi-hypothalami explanted from male rats. Activin-A stimulated GnRH release in a biphasic manner. The maximal effect was reached at a concentration of 10 ng/ml which increased GnRH output by about 75%. Inhibin abolished the stimulatory effect of a maximally effective concentration of activin-A in a dose-dependent manner, whereas alone it had no effect on GnRH output. As previously shown, testosterone (1 nmol/l) and dihydrotestosterone (DHT, 0.1 nmol/l) suppressed basal GnRH release, but only testosterone was able to inhibit the release of GnRH stimulated by activin-A. Since DHT is a non-aromatizable androgen, we evaluated whether the inhibitory effect of testosterone was due to its in vitro conversion into 17 beta-estradiol. The addition of 4-hydroxyandrostenedione, a steroidal aromatase inhibitor, did not influence the suppressive effect of testosterone on GnRH release stimulated by activin-A. In conclusion, activin-A stimulated hypothalamic GnRH release in vitro and this effect was abolished by inhibin and was blunted by testosterone. These findings suggest that activins may participate in the regulation of the hypothalamic-pituitary-gonadal axis by modulating GnRH release. The ability of testosterone to suppress the release of GnRH stimulated by activin-A indicates that this steroid has a potent negative feedback influence on GnRH release.

scholarly journals Pulsatile gonadotropin-releasing hormone release from hypothalamic explants of male marmoset monkeys compared with male rats

2010 ◽  
Vol 298 (1) ◽  
pp. R70-R78 ◽  
Author(s):  
Michael J. Woller ◽  
Pam L. Tannenbaum ◽  
Nancy J. Schultz-Darken ◽  
Bruce D. Eshelman ◽  
David H. Abbott
Keyword(s):  
Species Difference ◽  
Pulse Amplitude ◽  
Gonadotropin Releasing Hormone ◽  
Male Rats ◽  
Male Rat ◽  
Releasing Hormone ◽  
Gnrh Release ◽  
Marmoset Monkeys ◽  
Release Profiles

The present study was conducted to quantify in vitro gonadotropin-releasing hormone (GnRH) release parameters in the male marmoset. We established primary cultures of marmoset hypothalamic tissues for ∼2 days (marmosets) to assess GnRH release profiles in vitro in hypothalamic explants from testis-intact and gonadectomized males. Pulsatile GnRH release profiles were readily demonstrated from in vitro hypothalamic explants isolated from adult male marmoset monkeys. Gonadectomy of male marmosets resulted in elevated mean GnRH and pulse amplitude from hypothalamic explants on the 1st day of culture ( day 0). GnRH pulse amplitude increased by day 2 in ∼67% of hypothalamic explants from testis-intact marmosets, suggesting release from an endogenous regulator of GnRH. We also measured GnRH release profiles in vitro in hypothalamic explants from testis-intact and gonadectomized rats. Male rats showed no changes in any concentration or frequency release parameters for GnRH following gonadectomy or during successive days in culture. The present study represents a unique examination of GnRH release from male marmoset monkey hypothalamic tissue and compares release dynamics directly with those obtained from male rat, suggesting a species difference in feedback regulation of GnRH release.

scholarly journals Prolactin and Male Fertility: The Long and Short Feedback Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
M. K. Gill-Sharma
Keyword(s):  
Chromatin Condensation ◽  
Feedback Regulation ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Normal Men

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

scholarly journals Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms

2000 ◽  
Vol 279 (2) ◽  
pp. H610-H618 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Cerebral Arteries ◽  
Gonadal Hormones ◽  
No Synthase ◽  
Male Rats ◽  
Male Rat ◽  
Myogenic Tone ◽  
Channel Blockers ◽  
Luminal Diameter ◽  
Nos Inhibitor

Gender is known to influence the incidence and severity of cerebrovascular disease. In the present study, luminal diameter was measured in vitro in pressurized middle cerebral artery segments from male rats that were either untreated, orchiectomized (ORX), ORX with testosterone treatment (ORX+TEST), or ORX with estrogen treatment (ORX+EST). The maximal passive diameters (0 Ca2+ + 3 mM EDTA) of arteries from all four groups were similar. In endothelium-intact arteries, myogenic tone was significantly greater in arteries from untreated and ORX+TEST compared with arteries from either ORX or ORX+EST. During exposure to N G-nitro-l-arginine-methyl ester (l-NAME), an NO synthase (NOS) inhibitor, myogenic tone significantly increased in all groups. The effect of l-NAME was significantly greater in arteries from untreated and ORX+EST compared with arteries from ORX and ORX+TEST rats. Differences in myogenic tone between ORX and ORX+TEST persisted after inhibition of NOS. After endothelium removal or inhibition of the cyclooxygenase pathway combined with K+ channel blockers, myogenic tone differences between ORX and ORX+TEST were abolished. Wall thickness and forced dilation were not significantly different between arteries from ORX and ORX+TEST. Our data show that gonadal hormones affect myogenic tone in male rat cerebral arteries through NOS- and/or endothelium-dependent mechanisms.

Effect of streptozotocin-induced diabetes on bile acid sulfation in male rat liver

1984 ◽  
Vol 247 (3) ◽  
pp. G226-G230
Author(s):  
R. B. Kirkpatrick ◽  
B. G. Kraft
Keyword(s):  
Bile Acid ◽  
Specific Activity ◽  
Male Rats ◽  
Male Rat ◽  
Estrogen Metabolism ◽  
Normal Male ◽  
Activity Levels ◽  
Receptor Kinetics ◽  
Streptozotocin Induced Diabetes

The sulfation of bile acids is hormone dependent, being increased in females and ethynylestradiol (EE)-treated males compared with normal males. Diabetes causes significant alterations in estrogen metabolism and uterine estrogen receptor kinetics. Male rats were given streptozotocin (90 mg/kg) and diabetes was verified. An increase in hepatic bile acid sulfotransferase (BAST) activity was significant by 6 days and continued to increase to 29 days. This increase was prevented by insulin replacement. Administration of EE (6.0-600 micrograms X kg-1 X day-1) to normal male rats resulted in a significant increase in hepatic BAST activity; however, administration of similar doses of EE to diabetic males failed to further increase activity levels over the already-elevated levels in the diabetic controls. This increase in in vitro specific activity was accompanied by an increase in the biliary excretion of lithocholate 3-sulfate and taurolithocholate 3-sulfate in 21-day-diabetic animals. Bile flow and total bile acid excretion were also markedly increased in the diabetic animals. The data indicate that streptozotocin-induced diabetes causes a significant increase in hepatic BAST activity. These findings are consistent with an alteration in hepatic estrogen action in streptozotocin-induced diabetes.

The Effects of Melatonin and Serotonin on Blood Flow Fraction and Testosterone Metabolism in Selected Organs of the Male Rat

1973 ◽  
Vol 51 (5) ◽  
pp. 313-318 ◽  
Author(s):  
G. A. Kinson ◽  
Nora E. MacDonald ◽  
C-C. Liu
Keyword(s):  
Blood Flow ◽  
Nicotinamide Adenine Dinucleotide ◽  
Male Rats ◽  
Male Rat ◽  
Blood Levels ◽  
Testosterone Metabolism ◽  
Melatonin Administration ◽  
Distribution Of Cardiac Output ◽  
Fractional Distribution

The fractional distribution of cardiac output to the testes, adrenals, liver, and kidneys and the conversion of testosterone to 4-androstenedione by hepatic and renal homogenates in vitro were measured 4 weeks after implantation of male rats with melatonin and serotonin. The fractional blood flow to these organs was not significantly influenced by the indoles. There was, however, a tendency for the adrenal fraction to be lower in indole-treated rats. Blood levels of corticosterone in these animals were reduced, but significantly so only in the rats implanted with serotonin. The ability of liver preparations to metabolize testosterone in the presence of excess nicotinamide–adenine dinucleotide was enhanced after treatment with both indoles suggesting that at least one of the 17β-hydroxysteroid dehydrogenases had been stimulated. In the case of the kidney, melatonin administration gave rise to depression of the NAD-linked conversion whereas serotonin treatment caused reductions in testosterone conversions in the presence of either NAD or NADP.

scholarly journals In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin(116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat

2000 ◽  
pp. 406-410 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
LC Gonzalez ◽  
J Navarro ◽  
C Dieguez ◽  
...  
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Body Weight Gain ◽  
Biologically Active ◽  
Male Rats ◽  
Male Rat ◽  
Gh Secretion ◽  
Adult Rat ◽  
Testosterone Secretion

The obese gene (ob) product, leptin, has recently emerged as a key element in body weight homeostasis, neuroendocrine function and fertility. Identification of biologically active, readily synthesized fragments of the leptin molecule has drawn considerable attention, as they may provide a powerful tool for detailed characterization of the biological actions of leptin in different experimental settings. Recently, a fragment of mouse leptin protein comprising amino acids 116-130, termed leptin(116-130) amide, was shown to mimic the effects of the native molecule in terms of body weight gain and food intake, and to elicit LH and prolactin (PRL) secretion in vivo. As a continuation of our previous experimental work, the present study reports on the effects of leptin(116-130) amide on basal and stimulated testosterone secretion by adult rat testis in vitro. In addition, a comparison of the effects of human recombinant leptin and leptin(116-130) amide at the pituitary level on the patterns of LH, FSH, PRL and GH secretion is presented. As reported previously by our group, human recombinant leptin(10(-9)-10(-7)M) significantly inhibited both basal and human chorionic gonadotrophin (hCG)-stimulated testosterone secretion in vitro. Similarly, incubation of testicular tissue in the presence of increasing concentrations of leptin(116-130) amide (10(-9)-10(-5)M) resulted in a dose-dependent inhibition of basal and hCG-stimulated testosterone secretion; a reduction that was significant from a dose of 10(-7)M upwards. In addition, leptin(116-130) amide, at all doses tested (10(-9)-10(-5)M), significantly decreased LH and FSH secretion by incubated hemi-pituitaries from adult male rats. In contrast, in the same experimental protocol, recombinant leptin(10(-9)-10(-7)M) was ineffective in modulating LH and FSH release. Finally, neither recombinant leptin nor leptin(116-130) amide were able to change basal PRL and GH secretion in vitro. Our results confirm the ability of leptin, acting at the testicular level, to inhibit testosterone secretion, and map the effect to a domain of the leptin molecule that lies between amino acid residues 116 and 130. In addition, we provide evidence for a direct inhibitory action of leptin(116-130) amide on pituitary LH and FSH secretion, a phenomenon not observed for the native leptin molecule, in the adult male rat.

scholarly journals Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

2004 ◽  
Vol 181 (2) ◽  
pp. 223-231 ◽  
Author(s):  
V Viau ◽  
MJ Meaney
Keyword(s):  
Feedback Regulation ◽  
High Plasma ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosteroid Binding Globulin ◽  
Low Testosterone

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml), plasma adrenocorticotropin and beta-endorphin/beta-lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( approximately 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( approximately 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( approximately 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

scholarly journals Effects of Chronic Ethanol on Hepatic and Renal CYP2C11 in the Male Rat: Interactions with the Janus-Kinase 2-Signal Transducer and Activators of Transcription Proteins 5b Pathway

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3969-3976 ◽  
Author(s):  
T. M. Badger ◽  
M. J. J. Ronis ◽  
S. J. Frank ◽  
Y. Chen ◽  
L. He
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Serum Testosterone ◽  
Janus Kinase ◽  
Chronic Ethanol ◽  
Male Rats ◽  
Male Rat ◽  
Signal Transducer ◽  
Transduction Pathway

Abstract Chronic alcohol intake in male rats results in: 1) demasculinization of the GH pulse pattern; 2) reduced serum testosterone concentrations; and 3) decreased expression hepatic CYP2C11. Hepatic CYP2C11 expression is regulated by the male pattern of GH through the Janus-kinase/signal transducer and activators of transcription proteins (JAK/STAT) signal transduction pathway in the male rat. Renal CYP2C11 is regulated by testosterone, not GH. The involvement of the JAK/STAT5b signal transduction pathway in renal CYP2C11 signaling has not been studied. We tested the hypothesis that ethanol reduces CYP2C11 levels by interfering with the JAK/STAT5b pathway. Using a total enteral nutrition (TEN) model to feed rats a well-balanced diet, we have studied the effects of chronic ethanol intake (21 d) on hepatic and renal JAK/STAT pathway of adult male rats (8–10/group). We found decreased hepatic and renal expression of CYP2C11 in ethanol-fed rats with concomitant decreases in STAT5b and phospho-STAT5b, decreased in vitro hepatic STAT5b binding to a CYP2C11 promoter element and no effects on hepatic GHR levels. Ethanol caused tissue specific effects in phospho-JAK2 and JAK2, with increased levels in the liver, but decreased JAK2 expression in the kidney. We conclude that ethanol suppression of CYP2C11 expression is clearly associated with reductions in STAT5b levels, but not necessarily in reductions of JAK2 levels. The mechanisms underlying ethanol-induced suppression of STAT5b is yet to be determined, as is the question of whether this is secondary to hormonal effects or a direct ethanol effect.

Quantification of the Uncertainties in Extrapolating From In Vitro Androgen Receptor Antagonism to In Vivo Hershberger Assay Endpoints and Adverse Reproductive Development in Male Rats

2020 ◽  
Vol 176 (2) ◽  
pp. 297-311
Author(s):  
Leon E Gray ◽  
Johnathan R Furr ◽  
Christy S Lambright ◽  
Nicola Evans ◽  
Phillip C Hartig ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Adverse Outcome ◽  
In Utero ◽  
Male Rats ◽  
Male Rat ◽  
Rat Offspring ◽  
Hershberger Assay ◽  
Key Events

Abstract Multiple molecular initiating events exist that disrupt male sexual differentiation in utero including androgen receptor (AR) antagonism and inhibition of synthesis, and metabolism of fetal testosterone. Disruption of androgen signaling by AR antagonists in utero reduces anogenital distance (AGD) and induces malformations in F1 male rat offspring. We are developing a quantitative network of adverse outcome pathways that includes multiple molecular initiating events and key events linking anti-AR activities to permanent reproductive abnormalities. Here, our objective was to determine how accurately the EC50s for AR antagonism in vitro or ED50s for reduced tissue growth in the Hershberger assay (HA) (key events in the adverse outcome pathway) predict the ED50s for reduced AGD in male rats exposed in utero to AR antagonists. This effort included in-house data and published studies from the last 60 years on AR antagonism in vitro and in vivo effects in the HA and on AGD after in utero exposure. In total, more than 250 studies were selected and included in the analysis with data from about 60 potentially antiandrogenic chemicals. The ability to predict ED50s for key events and adverse developmental effects from the in vitro EC50s displays considerable uncertainty with R2 values for HA and AGD of < 6%. In contrast, there is considerably less uncertainty in extrapolating from the ED50s in the HA to the ED50s for AGD (R2 value of about 85%). In summary, the current results suggest that the key events measured in the HA can be extrapolated with reasonable certainty to predict the ED50s for the adverse in utero effects of antiandrogenic chemicals on male rat offspring.

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