Biphasic response in the secretion of gonadotrophin-releasing hormone in ovariectomized ewes injected with oestradiol

1989 ◽  
Vol 123 (3) ◽  
pp. 375-382 ◽  
Author(s):  
A. Caraty ◽  
A. Locatelli ◽  
G. B. Martin
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Sampling Period ◽  
Pulse Amplitude ◽  
Portal Blood ◽  
Blood Collection ◽  
Biphasic Response ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT In ovariectomized ewes, an injection of oestrogen initially inhibits the tonic secretion of LH, and then induces a large release of LH similar to the preovulatory surge in intact ewes. The pattern of hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) into the pituitary portal blood during this biphasic response to oestrogen was investigated in conscious, unrestrained, ovariectomized adult Ile-de-France ewes during the breeding season. The ewes were ovariectomized and implanted with cannulae for portal blood collection on the same day. Seven days later, portal and peripheral blood samples were collected simultaneously every 5 min for 25 h. The ewes were injected with oestradiol-17β (25 μg i.v. and 25 μg i.m.) 6·25 h after the start of sampling. GnRH and LH were measured by radioimmunoassay in portal and jugular plasma samples respectively. A clear pulsatile pattern of LH secretion was observed before the oestradiol injection in all ewes, followed by the typical biphasic decrease (negative feedback) and increase (positive feedback) in mean concentrations. The sampling period was divided, for analysis, into pretreatment, negative feedback and positive feedback phases. Before injection with oestradiol, the GnRH pulses were clearly defined in portal blood and always synchronized with LH pulses in the peripheral circulation. The frequency was 5·9 ± 0·6 pulses/6 h (mean ± s.e.m.), and the amplitude was 31·6±7·6 pmol/l. During negative feedback, both the frequency (4·2 ± 0·5 pulses/6 h, P<0·01) and amplitude (15·2 ± 4·6 pmol/l, P<0·05) of the GnRH pulses decreased. During positive feedback, there was a large surge in the concentration of GnRH, due primarily to an increase in pulse frequency (11·0±1·3 pulses/6 h, P<0·01). A change in pulse amplitude was not detected, but there was a large increase in the basal level of GnRH (P<0·05). As a consequence of the changes in frequency and amplitude of the pulses, the mean levels of GnRH before injection with oestradiol (5·3 ± 1·0 pmol/l) differed (P<0·05) from those during negative (3·8±0·5 pmol/l) and positive (18·9±4·7 pmol/l) feedback phases. These results show that the biphasic pattern of LH secretion induced by oestrogen injection in short-term ovariectomized ewes is caused by parallel changes in the secretion of GnRH as well as changes in pituitary responsiveness to GnRH. An abrupt increase in the frequency of GnRH pulses appears to be a key component of the positive feedback mechanism which elicits the oestradiol-induced surges of both GnRH and LH. Journal of Endocrinology (1989) 123, 375–382

Secretion rates and short-term patterns of gonadotrophin-releasing hormone, FSH and LH in the normal stallion in the breeding season

1988 ◽  
Vol 117 (2) ◽  
pp. 197-206 ◽  
Author(s):  
C. H. G. Irvine ◽  
S. L. Alexander
Keyword(s):  
Breeding Season ◽  
Venous Blood ◽  
Pulse Amplitude ◽  
Interpulse Interval ◽  
Statistical Testing ◽  
Pulse Interval ◽  
Apparent Difference ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

ABSTRACT Pituitary venous blood was collected by a painless non-surgical cannulation method from five ambulatory stallions at 5-min intervals for 5–6 h during the breeding season. In four adult stallions, statistical analysis showed that pulses of gonadotrophin-releasing hormone (GnRH) and LH were coincident (P <0·01), as were pulses of FSH and LH (P <0·05). Furthermore, the patterns of changes in concentration of FSH and LH were highly correlated in each of the four stallions. However, seemingly ineffective pulses of GnRH were also observed, with 28% of GnRH pulses failing to induce a significant gonadotrophin pulse. In the four adult stallions the amplitude of pituitary venous gonadotrophin pulses varied markedly but no correlation with GnRH pulse amplitude was observed. Peak secretion of FSH, but not LH, during pulses was correlated with the length of the interpulse interval. Consequently, the ratio of FSH to LH during peaks was least (P <0·02) when the interpulse interval was 30 min or less. Thus, differential FSH and LH secretion was achieved within a constant steroid milieu. Two stallions had regular contact with oestrous mares, and in these horses the secretion of GnRH and gonadotrophins occurred almost continuously with rapid, rhythmic pulses superimposed upon a tonic background. Mean (± s.d.) interval between GnRH pulses was 31·4 ± 9·8 min and 27·7 ± 10·1 min. This secretory pattern was not observed in the two stallions which had infrequent contact with oestrous mares, although the small numbers precluded statistical testing of this apparent difference. No GnRH pulses were observed in one of these stallions, while in the other mean (± s.d.) GnRH pulse interval was 45·0 ± 48·7 min, the large variance being partly due to rapid pulses during a period in which the stallion teased mares. The fifth stallion was pubertal, and GnRH and LH secretion occurred in 15 and 0% of samples respectively, while low levels of FSH secretion were observed in 37% of samples and jugular testosterone levels were immeasurably low. We conclude that there is a statistically significant synchrony between pulses of GnRH, LH and FSH in the pituitary venous blood of stallions. Furthermore, decreasing intervals between gonadotrophin pulses result in a significant reduction in secretion of FSH but not LH. J. Endocr. (1988) 117, 197–206

Effects of modifying gonadotrophin-releasing hormone input before and after the oestrogen-induced LH surge in ovariectomized ewes with hypothalamo-pituitary disconnection

1990 ◽  
Vol 127 (2) ◽  
pp. 223-233 ◽  
Author(s):  
D. J. Phillips ◽  
J. T. Cummins ◽  
I. J. Clarke
Keyword(s):  
Continuous Infusion ◽  
Positive Feedback ◽  
Pulse Amplitude ◽  
Secretory Component ◽  
Similar Response ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Before And After ◽  
Gonadotrophin Releasing Hormone ◽  
Sufficient Magnitude

ABSTRACT The patterns of gonadotrophin-releasing hormone (GnRH) input to the pituitary gland that affect the expression of a positive-feedback event by oestrogen on LH secretion were investigated in ovariectomized ewes with hypothalamo-pituitary disconnection (HPD). In experiment 1, ovariectomized HPD ewes were given hourly i.v. pulses of 250 ng GnRH and an i.m. injection of 50 μg oestradiol benzoate (OB). The ewes were given a bolus pulse of 2·25 μg GnRH 16 h after injection of OB, followed by half-hourly pulses of 250 ng GnRH for 14 h (treatment A). The LH surge response was significantly (P <0·05) greater in these ewes compared with that in ewes given a continuous infusion of GnRH (250 ng/h) after the OB injection, followed by a continuous infusion of 500 ng GnRH/h after the bolus pulse of GnRH (treatment B). When no GnRH was administered after the OB injection, except for the bolus pulse of GnRH (treatment C), the surge response was significantly (P <0·05) reduced compared with that in treatment A, and was reduced compared with treatment B. These data suggest that GnRH pulses are important in the generation of the OB-induced LH surge, but that a baseline secretory component can prime the pituitary to some extent. experiment 2, a doubling of the continuous infusion dose of GnRH used in treatment B to 500 ng/h before the bolus pulse of GnRH and to 1 μg/h afterwards (treatment D) gave a similar response compared with treatment A, suggesting that if the baseline input of GnRH is of sufficient magnitude, it can overcome the lack of pulsatile input. In experiment 3, halving the GnRH pulse amplitude used in treatment A from 250 to 125 ng (treatment E) did not reduce the LH surge response, implying that when the GnRH input is in a pulsatile mode, the amplitude of GnRH pulses is less important than the pulsatile nature per se. In experiment 4, removal of GnRH input after the bolus pulse of GnRH (treatment F) significantly (P <0·05) reduced the surge response compared with when pulses were maintained (treatment A), indicating that GnRH input is still required once the LH surge has been initiated. Collectively, these experiments show that several forms of GnRH delivery, both pulsatile and baseline, can result in the full expression of a positive-feedback response in ovariectomized ewes treated with oestrogen. Journal of Endocrinology (1990) 127, 223–233

scholarly journals Evidence that Orphanin FQ Mediates Progesterone Negative Feedback in the Ewe

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4249-4258 ◽  
Author(s):  
Casey C Nestor ◽  
Lique M. Coolen ◽  
Gail L. Nesselrod ◽  
Miro Valent ◽  
John M. Connors ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Luteal Phase ◽  
Arcuate Nucleus ◽  
Pulse Amplitude ◽  
Estrogen Receptor Α ◽  
Pulse Frequency ◽  
Orphanin Fq ◽  
High Degree ◽  
Lh Secretion

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.

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.

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.

Induction of luteinized unruptured follicles in the rat after injection of luteinizing hormone early in pro-oestrus

1995 ◽  
Vol 132 (1) ◽  
pp. 91-96 ◽  
Author(s):  
John AM Mattheij ◽  
Hans JM Swarts
Keyword(s):  
Luteinizing Hormone ◽  
The Netherlands ◽  
Small Dose ◽  
Great Majority ◽  
Gnrh Analogue ◽  
Releasing Hormone ◽  
Animal Physiology ◽  
Cause Of Formation ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

Mattheij JAM, Swarts HJM. Induction of luteinized unruptured follicles in the rat after injection of luteinizing hormone early in pro-oestrus. Eur J Endocrinol 1995;132:91–6. ISSN 0804–4643 The cause of formation of luteinized unruptured follicles (LUF) is unknown. Formation of LUF was studied after injection of a varying small dose of luteinizing hormone (LH) with or without subsequent injection of gonadotrophin-releasing hormone (GnRH); in addition, the effect of suppression of prolactin on LUF formation was studied. Luteinization without ovulation occurred in virtually all graafian follicles, if 0.5–1.0 μg of LH was injected some hours before the presumed endogenous LH surge (suppressed by Nembutal); with increasing doses of LH progressively increasing numbers of ovulations were observed. If in early pro-oestrus 1 μg of GnRH was given 4 h after 1 μg of LH, formation of LUF was partly prevented; if the interval between LH and GnRH was 8 h or more, the great majority of graafian follicles developed into LUF. If early in pro-oestrus 1 μg of LH was given and 8 h later 0.1 μg of a potent GnRH analogue, about 50% of the follicles became LUF; in similarly treated rats, suppression of prolactin by ergocryptine reduced but did not prevent LUF formation. The data support the idea that deficient LH secretion in the period before ovulation may be involved in the formation of LUF. John AM Mattheij, Department of Human and Animal Physiology, Haarweg 10, 6709 PJ Wageningen, The Netherlands

Infantile ovariectomy potentiates the stimulatory effect of oestrogen/progesterone on LH secretion in the rat

1985 ◽  
Vol 106 (1) ◽  
pp. 133-139 ◽  
Author(s):  
M. Wilkinson ◽  
R. Bhanot
Keyword(s):  
Inhibitory Mechanism ◽  
Releasing Hormone ◽  
Oestradiol Benzoate ◽  
Gonadotrophin Releasing Hormone ◽  
Prepubertal Rats ◽  
Lh Secretion

ABSTRACT Ovariectomy of prepubertal rats (9 days of age) eliminates the ability of the opiate peptide FK 33-824 to inhibit LH secretion when tested 19 days later. We have investigated whether this removal of opiate inhibition would modify the LH/FSH response to stimulation with oestradiol benzoate/progesterone priming. Ovariectomy of rats during infancy (9 days after birth) amplifies the stimulatory effects of these steroids on LH/FSH secretion when tested 19 days later. This amplification was not seen in rats ovariectomized before (day 24) or after puberty (day 43) and tested 19 days later. The pituitary content of LH/FSH does not appear to contribute to this phenomenon, though increased responsiveness to injected gonadotrophin-releasing hormone (GnRH) is clearly involved; ovariectomy at day 9 is considerably more effective than ovariectomy at day 24 of life in enhancing the response to GnRH. We conclude that infantile ovariectomy either removes, or prevents the development of, a hypothalamic inhibitory mechanism which normally modulates the responsiveness of the pituitary to stimulation with GnRH. J. Endocr. (1985) 106, 133–139

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

scholarly journals Gonadotropin-Inhibitory Hormone (GnIH) Secretion into the Ovine Hypophyseal Portal System

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3368-3375 ◽  
Author(s):  
Jeremy T. Smith ◽  
I. Ross Young ◽  
Johannes D. Veldhuis ◽  
Iain J. Clarke
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Portal Blood ◽  
Portal System ◽  
Dorsomedial Nucleus ◽  
Cellular Targets ◽  
Nonbreeding Season ◽  
Peripheral Blood Plasma ◽  
Gonadotropin Inhibitory Hormone ◽  
Lh Secretion

GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary-disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.

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