Effects of corticotropin-releasing hormone and its antagonist on the gene expression of gonadotrophin-releasing hormone (GnRH) and GnRH receptor in the hypothalamus and anterior pituitary gland of follicular phase ewes

2011 ◽  
Vol 23 (6) ◽  
pp. 780 ◽  
Author(s):  
Magdalena Ciechanowska ◽  
Magdalena Łapot ◽  
Tadeusz Malewski ◽  
Krystyna Mateusiak ◽  
Tomasz Misztal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Follicular Phase ◽  
Gnrh Receptor ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion ◽  
Crh Receptors

There is no information in the literature regarding the effect of corticotropin-releasing hormone (CRH) on genes encoding gonadotrophin-releasing hormone (GnRH) and the GnRH receptor (GnRHR) in the hypothalamus or on GnRHR gene expression in the pituitary gland in vivo. Thus, the aim of the present study was to investigate, in follicular phase ewes, the effects of prolonged, intermittent infusion of small doses of CRH or its antagonist (α-helical CRH 9-41; CRH-A) into the third cerebral ventricle on GnRH mRNA and GnRHR mRNA levels in the hypothalamo–pituitary unit and on LH secretion. Stimulation or inhibition of CRH receptors significantly decreased or increased GnRH gene expression in the hypothalamus, respectively, and led to different responses in GnRHR gene expression in discrete hypothalamic areas. For example, CRH increased GnRHR gene expression in the preoptic area, but decreased it in the hypothalamus/stalk median eminence and in the anterior pituitary gland. In addition, CRH decreased LH secretion. Blockade of CRH receptors had the opposite effect on GnRHR gene expression. The results suggest that activation of CRH receptors in the hypothalamus of follicular phase ewes can modulate the biosynthesis and release of GnRH through complex changes in the expression of GnRH and GnRHR genes in the hypothalamo–anterior pituitary unit.

Relationship between gonadotrophin subunit gene expression, gonadotrophin-releasing hormone receptor content and pituitary and plasma gonadotrophin concentrations during the rebound release of FSH after treatment of ewes with bovine follicular fluid during the luteal phase of the cycle

1992 ◽  
Vol 8 (2) ◽  
pp. 109-118 ◽  
Author(s):  
J. Brooks ◽  
W. J. Crow ◽  
J. R. McNeilly ◽  
A. S. McNeilly
Keyword(s):  
Follicular Fluid ◽  
Luteal Phase ◽  
Gnrh Receptor ◽  
Mrna Levels ◽  
Α Subunit ◽  
Luteal Regression ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion ◽  
Cessation Of Treatment

ABSTRACT The modulation of FSH secretion at the beginning and middle of the follicular phase of the cycle represents the key event in the growth and selection of the preovulatory follicle. However, the mechanisms that operate within the pituitary gland to control the increased release of FSH and its subsequent inhibition in vivo remain unclear. Treatment of ewes with bovine follicular fluid (bFF) during the luteal phase has been previously shown to suppress the plasma concentrations of FSH and, following cessation of treatment on day 11, a rebound release of FSH occurs on days 12 and 13. When luteal regression is induced on day 12, this hypersecretion of FSH results in an increase in follicle growth and ovulation rate. To investigate the mechanisms involved in the control of FSH secretion, ewes were treated with twice daily s.c. injections of 5 ml bFF on days 3–11 of the oestrous cycle and luteal regression was induced on day 12 with prostaglandin (PG). The treated ewes and their controls were then killed on day 11 (luteal), or 16 or 32h after PG and their pituitaries removed and halved. One half was analysed for gonadotrophin and gonadotrophin-releasing hormone (GnRH) receptor content. Total pituitary RNA was extracted from the other half and subjected to Northern analysis using probes for FSH-β, LH-β and common α subunit. Frequent blood samples were taken and assayed for gonadotrophins. FSH secretion was significantly (P<0.01) reduced during bFF treatment throughout the luteal phase and then significantly (P<0.01) increased after cessation of treatment, with maximum secretion being reached 18– 22h after PG, and then declining towards control values by 32h after PG. A similar pattern of LH secretion was seen after bFF treatment. Pituitary FSH content was significantly (P<0.05) reduced by bFF treatment at all stages of the cycle. No difference in the pituitary LH content was seen. The increase in GnRH receptor content after PG in the controls was delayed in the treated animals. Analysis of pituitary mRNA levels revealed that bFF treatment significantly (P<0.01) reduced FSH-β mRNA levels in the luteal phase. Increased levels of FSH-β, LH-β and α subunit mRNA were seen 16h after PG in the bFF-treated animals, at the time when FSH and LH secretion from the pituitary was near maximum. These results suggest that the rebound release of FSH after treatment with bFF (as a source of inhibin) is related to a rapid increase in FSH-β mRNA, supporting the concept that the rate of FSH release is directly related to the rate of synthesis.

Gonadotrophin-releasing hormone (GnRH) overcomes GnRH antagonist-induced suppression of LH secretion in primates

1986 ◽  
Vol 110 (1) ◽  
pp. 145-150 ◽  
Author(s):  
G. R. Marshall ◽  
F. Bint Akhtar ◽  
G. F. Weinbauer ◽  
E. Nieschlag
Keyword(s):  
Gnrh Antagonist ◽  
Receptor Occupancy ◽  
Gnrh Receptor ◽  
Dependent Manner ◽  
Response Curves ◽  
Gnrh Antagonists ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT If the suppressive effects of gonadotrophin-releasing hormone (GnRH) antagonists on gonadotrophin secretion are mediated through GnRH-receptor occupancy alone, it should be possible to restore serum gonadotrophin levels by displacing the antagonist with exogenous GnRH. To test this hypothesis, eight adult crab-eating macaques (Macaca fascicularis), weight 4·7–7·6 kg, were subjected to the following treatment regimens. A GnRH-stimulation test was performed before and 4, 12 and 24 h after a single s.c. injection of the GnRH antagonist (N-Ac-d-p-Cl-Phe1,2,d-Trp3,d-Arg6,d-Ala10)-GnRH (ORG 30276). The stimulation tests were performed with 0·5, 5·0 or 50 μg GnRH given as a single i.v. bolus. Blood was taken before and 15, 30 and 60 min after each bolus for analysis of bioactive LH and testosterone. The GnRH-challenging doses were given as follows: 0·5 μg GnRH was injected at 0 and 4 h, followed by 5·0 μg after 12 h and 50 μg after 24 h. One week later, 5·0 μg GnRH were given at 0 and 4 h, followed by 50 μg after 12 h and 0·5 μg after 24 h. Finally, after another week, the GnRH challenges began with 50 μg at 0 and 4 h, followed by 0·5 μg at 12 h and 5·0 μg at 24 h. This design permitted comparison of the LH and testosterone responses with respect to the dose of GnRH and the time after administration of GnRH antagonist. The areas under the response curves were measured and statistical evaluation was carried out by means of non-parametric two-way analysis of variance followed by the multiple comparisons of Wilcoxon and Wilcox. Four hours after the antagonist was injected, the LH and testosterone responses to all three doses of GnRH were suppressed. At the lowest dose of GnRH (0·5 μg) the responses remained reduced even after 24 h, whereas the higher doses of GnRH elicited an LH and testosterone response at 12 and 24 h which was not significantly different from that at 0 h. These data demonstrate that the suppression of LH secretion by a GnRH antagonist in vivo can be overcome by exogenously administered GnRH in a dose- and time-dependent manner, thus strongly supporting the contention that GnRH antagonists prevent gonadotrophin secretion by GnRH-receptor occupancy. J. Endocr. (1986) 110, 145–150

Exogenous gonadotrophin-releasing hormone (GnRH) stimulates LH secretion in male monkeys (Macaca fascicularis) treated chronically with high doses of a GnRH antagonist

1992 ◽  
Vol 133 (3) ◽  
pp. 439-445 ◽  
Author(s):  
G. F. Weinbauer ◽  
P. Hankel ◽  
E. Nieschlag
Keyword(s):  
Gnrh Antagonist ◽  
Prolonged Exposure ◽  
Receptor Occupancy ◽  
Gnrh Receptor ◽  
Dependent Manner ◽  
Releasing Hormone ◽  
Testosterone Secretion ◽  
Stimulation Tests ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT We reported previously that after a single injection of a gonadotrophin-releasing hormone (GnRH) antagonist to male monkeys, exogenous GnRH stimulated LH secretion in a time- and dose-dependent manner, indicating that GnRH antagonist-induced blockade of LH secretion resulted from pituitary GnRH receptor occupancy. The present study was performed to investigate whether GnRH can also restore a blockade of LH and testosterone secretion during chronic GnRH antagonist administration. Four adult male cynomolgus monkeys (Macacafascicularis) received daily s.c. injections of the GnRH antagonist [N-Ac-d-pCl-Phe1,2,d-TRP3,d-Arg6,d-Ala10]-GnRH (ORG 30276) at a dose of 1400–1600 μg/kg for 8 weeks. Before the GnRH antagonist was given and during weeks 3 and 8 of treatment, pituitary stimulation tests were performed with 0·5, 5, 50 and 500 μg synthetic GnRH, administered in increasing order at intervals of 24 h. At 8 weeks, a dose of 1000 μg GnRH was also given. All doses of GnRH significantly (P < 0·05) stimulated serum concentrations of bioactive LH (3- to 8-fold) and testosterone (2·6- to 3·8-fold) before the initiation of GnRH antagonist treatment. After 3 weeks of GnRH antagonist treatment, only 50 and 500 μg GnRH doses were able to increase LH and testosterone secretion. Release of LH was significantly (P < 0·05) more elevated with 500 μg compared with 50 μg GnRH. After 8 weeks, only the highest dose of 1000 μg elicited a significant (P < 0·05) rise in LH secretion. Basal hormone levels just before the bolus injection of GnRH were similar (P > 0·10–0·80). This finding eliminated the possibility that the increasing doses of GnRH had primed the pituitary thereby resulting in higher stimulatory effects of the larger doses of GnRH. In conclusion, the present data indicate that, even after prolonged exposure to a GnRH antagonist, the pituitary retains some degree of responsiveness to GnRH. This observation supports the view that the inhibitory effects of chronic GnRH antagonist treatment are also mediated, at least in part, by occupancy of the pituitary GnRH receptor rather than by receptor down-regulation. Journal of Endocrinology (1992) 133, 439–445

Effect of cortisol on the response to gonadotrophin releasing hormone in the boar

1983 ◽  
Vol 97 (1) ◽  
pp. 75-81 ◽  
Author(s):  
R. M. Liptrap ◽  
J. I. Raeside
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Plasma Cortisol ◽  
Intramuscular Injection ◽  
Anterior Pituitary Gland ◽  
Nacl Solution ◽  
Hormonal Response ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Different Doses

The effect of intracarotid perfusion of 40 mg cortisol for 1 h on the hormonal response to three different doses of an intramuscular injection of synthetic gonadotrophin releasing hormone (GnRH) was compared to that of GnRH injected during intracarotid perfusion with 0·9% (w/v) NaCl solution in five boars. The increase in production of LH, above basal values, in response to injection of 0·25 μg GnRH midway through perfusion was only slightly greater (P > 0·05) in boars receiving cortisol compared to that when the same boars received saline. When 0·5 μg GnRH was injected midway through perfusion, a significantly greater (P<0·05) increase in production of LH above basal levels occurred during cortisol administration than occurred when saline was given. Injection of 1·0 μg GnRH in boars during cortisol perfusion resulted in significantly greater (P<0·01) production of LH, above basal levels, compared to the increase above basal levels that resulted when this dose of GnRH was given during intracarotid saline treatment. Increases in plasma values of testosterone reflected the increases in levels of LH. The results suggest that acute elevations in plasma cortisol may, under some circumstances, enhance the increased production of LH in the boar by increasing the responsiveness of the anterior pituitary gland to GnRH.

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin

2019 ◽  
Vol 31 (6) ◽  
pp. 1134 ◽  
Author(s):  
Chooi Yeng Lee ◽  
ShengYun Li ◽  
Xiao Feng Li ◽  
Daniel A. E. Stalker ◽  
Claire Cooke ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridisation ◽  
Releasing Hormone ◽  
Related Peptide ◽  
Concomitant Reduction ◽  
Intracerebroventricular Injections ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15μgkg−1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

OESTRADIOL RECEPTORS IN THE RAT ANTERIOR PITUITARY GLAND DURING THE OESTROUS CYCLE: QUANTITATION OF RECEPTOR ACTIVITY IN RELATION TO GONADOTROPHIN RELEASING HORMONE-MEDIATED LUTEINIZING HORMONE RELEASE

1978 ◽  
Vol 76 (2) ◽  
pp. 211-218 ◽  
Author(s):  
K. K. SEN ◽  
K. M. J. MENON
Keyword(s):  
Pituitary Gland ◽  
Binding Sites ◽  
Anterior Pituitary ◽  
Anterior Pituitary Gland ◽  
Oestrous Cycle ◽  
Hormone Release ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Stimulation Of

Specific oestradiol binding to a receptor in nuclear and cytosol fractions of the rat anterior pituitary gland and pituitary responsiveness to gonadotrophin releasing hormone (GnRH) during the oestrous cycle have been studied. To accomplish this, both unoccupied and occupied oestradiol-binding sites in the cytosol and oestradiol-binding sites in the nucleus and total cell were measured during the oestrous cycle. The concentration of unoccupied and occupied sites and total oestradiol binding in the cytosol fluctuated during the cycle. At pro-oestrus, the concentration of cytosol receptor was diminished by about 40% and replenishment occurred during oestrus. On the other hand, a profound increase in concentrations of cellular and nuclear receptors occurred at pro-oestrus. Administration of GnRH significantly stimulated LH release at all stages of the cycle. The maximum stimulation of LH release by GnRH was observed at 13.00 h of pro-oestrus. From these studies, it is concluded that pituitary responsiveness to exogenous GnRH during pro-oestrus parallels the changes in the content of oestrogen receptors in the cytosol and nucleus.

An unexpected increase in pituitary sensitivity to gonadotropin releasing hormone after treatment with porcine follicular fluid (inhibin) in immature hemicastrate rats

1980 ◽  
Vol 58 (2) ◽  
pp. 220-222 ◽  
Author(s):  
M. Wilkinson ◽  
W. H. Moger ◽  
Liisa K. Selin
Keyword(s):  
Follicular Fluid ◽  
Anterior Pituitary ◽  
Chronic Treatment ◽  
Follicle Stimulating Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Increased Sensitivity ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

Porcine follicular fluid (PFF) contains a factor (inhibin or folliculostatin) which is reported to selectively inhibit the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Chronic treatment of hemicastrate immature rats with PFF is able to partially inhibit the FSH-mediated hypertrophy of the remaining testis. However, the pituitaries from PFF-treated rats are paradoxically very sensitive to stimulation with gonadotrophin-releasing hormone (GnRH) and secrete significantly more FSH than control glands. Furthermore, this increased sensitivity results in a large increase in luteinizing hormone (LH) secretion. These observations suggest that under certain circumstances PFF is not selective for FSH and that it surprisingly stimulates rather than inhibits gonadotrophin secretion.

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