The oestrogen-induced surge of LH requires a 'signal' pattern of gonadotrophin-releasing hormone input to the pituitary gland in the ewe

1989 ◽  
Vol 122 (1) ◽  
pp. 127-134 ◽  
Author(s):  
I. J. Clarke ◽  
J. T. Cummins ◽  
M. Jenkin ◽  
D. J. Phillips
Keyword(s):  
Pituitary Gland ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Gnrh Secretion ◽  
Signal Pattern ◽  
Oestradiol Benzoate ◽  
Gonadotrophin Releasing Hormone ◽  
Baseline Values

ABSTRACT Two experiments were conducted with ovariectomized and hypothalamo-pituitary disconnected (HPD) ewes to ascertain the pattern of inputs, to the pituitary gland, of gonadotrophin-releasing hormone (GnRH) necessary for the full expression of an oestrogen-induced LH surge. The standard GnRH replacement to these sheep was to give pulses of 250 ng (i.v.) every 2 h; at the onset of experimentation, pulses were given hourly. In experiment 1, groups of sheep (n = 7) were given an i.m. injection of 50 μg oestradiol benzoate, and after 10 h the GnRH pulse frequency or pulse amplitude was doubled. Monitoring of plasma LH concentrations showed that a doubling of pulse frequency produced a marked increase in baseline values, whereas a doubling of amplitude had little effect on the LH response. In a second experiment, ovariectomized HPD sheep that had received hourly pulses of GnRH for 16 h after an i.m. injection of oil or 50 μg oestradiol benzoate were given either a 'bolus' (2·25 μg GnRH) or a 'volley' (500 ng GnRH pulses 10 min apart for 30 min, plus a 500 ng pulse 15 min later). Both groups then received GnRH pulses (250 ng) every 30 min for the next 13 h. Oestrogen enhanced the LH responses to the GnRH treatments, and the amount of LH released was similar in ovariectomized HPD ewes given oestrogen plus bolus or volley GnRH treatments and ovariectomized hypothalamopituitary intact ewes given oestrogen. These results suggest that the oestrogen-induced LH surge is initiated by a 'signal' pattern of GnRH secretion from the hypothalamus. Journal of Endocrinology (1989) 122, 127–134

Gonadotrophin-releasing hormone secretion (GnRH) in anoestrous ewes and the induction of GnRH surges by oestrogen

1988 ◽  
Vol 117 (3) ◽  
pp. 355-360 ◽  
Author(s):  
I. J. Clarke
Keyword(s):  
Hormone Secretion ◽  
Sampling Period ◽  
Pulse Frequency ◽  
Marked Rise ◽  
Oestrogen Treatment ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Gnrh Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Large Pulse

ABSTRACT Anoestrous ewes were studied to determine the pattern of secretion of gonadotrophin-releasing hormone (GnRH) in the resting state and following a single i.m. injection of 50 μg oestradiol benzoate. In three out of four untreated ewes, two or three GnRH pulses were observed over a 6-h sampling period. In the fourth sheep the GnRH pulse frequency was higher (six pulses/6 h), but GnRH pulse amplitudes were lower. Following oestrogen treatment, GnRH pulses continued until the occurrence of an LH surge 12 h later. In five out of six sheep sampled during the oestrogen-induced LH surge a marked rise in GnRH secretion was seen. In the sixth ewe a large pulse of GnRH was seen at the start of the LH surge followed by increased GnRH secretion. It is concluded that GnRH pulse frequency is lower, generally, during anoestrus than during the mating season, and that oestrogen treatment of anoestrous ewes causes a surge in GnRH secretion unlike that seen in similarly treated ovariectomized ewes or the natural cyclic preovulatory changes in GnRH secretion. J. Endocr. (1988) 117, 355–360

Suppression of LH response to gonadotrophin-releasing hormone or oestradiol by ACTH(1–24) treatment in anoestrous ewes

1988 ◽  
Vol 118 (2) ◽  
pp. 193-197 ◽  
Author(s):  
H. Dobson ◽  
S. A. Essawy ◽  
M. G. S. Alam
Keyword(s):  
Plasma Concentrations ◽  
Suppressive Effect ◽  
Reproductive Efficiency ◽  
Adrenocorticotrophic Hormone ◽  
Releasing Hormone ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Baseline Values ◽  
Lh Secretion

ABSTRACT Stress is known to result in lowered female reproductive efficiency. The objective of this study was to examine how increased pituitary-adrenal activity may influence gonadotrophin release in anoestrous ewes. Various doses (0·06–1·0 mg) of a synthetic adrenocorticotrophic hormone (ACTH(1–24)) preparation were injected into ewes 30 min or 3 h before an i.v. injection of 500 ng gonadotrophin-releasing hormone (GnRH). The LH response to GnRH given 30 min after ACTH(1–24) was similar to that after GnRH alone, whereas the response 3 h after ACTH(1–24) was significantly lower, irrespective of the dose of ACTH(1–24). At 30 min and 3 h after ACTH(1–24) the concentrations of cortisol exceeded 50 nmol/l compared with baseline values of < 10 nmol/l. The effect of ACTH(1–24) on oestradiol-induced LH release was also examined. Those ewes receiving 0·8 mg ACTH(1–24) depot and 50 μg oestradiol benzoate simultaneously had a preovulatory-type increase in LH 14–20 h later, similar to when oestradiol benzoate was given alone. None of the ewes receiving an additional 0·8 mg ACTH(1–24) depot 10 h after oestradiol benzoate had increases in LH concentration. The cortisol concentrations in all ewes receiving either one or two injections of ACTH(1–24) were > 35 nmol/l at 10 h after the oestradiol injection. However, concentrations of progesterone increased from 0·9 ± 0·3 (s.e.m.) nmol/l at the time of the second ACTH(1–24) injection to 2·1 ±0·3 nmol/l after 2 h. In summary, it would appear that the suppressive effect of ACTH(1–24) on LH secretion induced by GnRH or oestradiol in the anoestrous ewe is not dependent on increased plasma concentrations of cortisol. J. Endocr. (1988) 118, 193–197

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

Neurophysiological control of the secretion of gonadotrophin-releasing hormone and luteinizing hormone in the sheep--a review

1991 ◽  
Vol 3 (2) ◽  
pp. 137 ◽  
Author(s):  
JC Thiery ◽  
GB Martin
Keyword(s):  
Luteinizing Hormone ◽  
Steroid Receptors ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Neural Pathways ◽  
Releasing Hormone ◽  
Diagonal Band ◽  
Gonadotrophin Secretion ◽  
Gnrh Neurons ◽  
Gonadotrophin Releasing Hormone

The anterior pituitary gland secretes pulses of luteinizing hormone (LH) in response to pulses of gonadotrophin-releasing hormone (GnRH) released into the hypophysial portal blood by the hypothalamus. The pulsatile nature of the secretions is very important because the frequency of the pulses is directly related to the activity of the GnRH neurons. We can therefore take advantage of this phenomenon to develop mechanistic interpretations of responses to experimental treatments designed to unravel the neural pathways that influence what is, arguably, the most important individual signal controlling the activity of the reproductive system. We might also resolve the disagreements in the literature covering the neuropharmacology of gonadotrophin secretion. In this review, we describe work towards this end in the sheep. Most (95%) of the 2500 GnRH cell bodies in the sheep brain are located in a region covering the anterior hypothalamus, the medial preoptic area, the diagonal band of Broca, and the septum. The axons of up to 50% of these cells terminate in the organum vasculosum of the lamina terminalis. The remainder terminate in the median eminence and form the final common pathway for the many factors that affect gonadotrophin secretion. Among the factors known to affect the frequency of the pulses (or the activity of the GnRH neurons) are nutrition, pheromones, photoperiod and gonadal steroids (negative and positive feedback). Factors that affect GnRH pulse amplitude are more difficult to determine because variations in pituitary responsiveness prevent the use of LH patterns as a 'bioassay'. Techniques developed recently have allowed the direct measurement of GnRH pulse amplitude and revealed inhibitory effects of oestradiol, but we do not know whether this effect is due to a reduction in the amount of GnRH released by each neurone or a reduction in the number of neurones releasing a pulse. It is unlikely that the factors that alter pulse frequency do so by directly affecting the GnRH cells. For example, it is obvious that other cells, with specific receptors for pheromonal or nutritional stimuli, formulate a signal that is transferred to the GnRH cells via interneurones. Similarly, it is likely that a hypothalamic clock intervenes between photoperiodic inputs and GnRH output. Opioidergic neurons have been proposed as a link in this system, but the complexity of their action makes it unlikely that they directly affect the GnRH neurons. The responses to steroids are simple and rapid, but steroid receptors have not been found in GnRH cells, so at least one other set of interneurones is involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulsatile administration of gonadotrophin-releasing hormone stimulates, in oestrogen-treated anaesthetized ovariectomized ewes, a surge release of LH qualitatively and quantitatively different from that induced by oestradiol in conscious ovariectomized ewes

1988 ◽  
Vol 116 (1) ◽  
pp. 143-148 ◽  
Author(s):  
P. J. Wright ◽  
I. J. Clarke
Keyword(s):  
Plasma Concentrations ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Treatment Regimens ◽  
Oestradiol Benzoate ◽  
Pulsatile Administration ◽  
Gonadotrophin Releasing Hormone ◽  
Induction Of Anaesthesia ◽  
Lh Secretion ◽  
Conscious Control

ABSTRACT The nature of the gonadotrophin-releasing hormone (GnRH) stimulus of the pituitary necessary for the oestrogen-induced plasma LH surge was studied in ovariectomized ewes. The sheep were treated with oestradiol benzoate (50 μg i.m.) at 0 h, and the hypothalamic contribution to the LH surge was blocked by pentobarbitone anaesthesia over the time during which the surge was expected (11–31 h). Pituitary responsiveness to exogenous GnRH (100 ng) administered i.v. in a pulsatile mode (once per hour or once per 20 min) over the period 15–30 h was assessed from plasma concentrations of LH. Neither of the GnRH treatments induced patterns of LH secretion similar to those seen in conscious ovariectomized ewes given oestrogen only. Plasma LH secretion in response to hourly GnRH pulses was less (P<0·01) than that associated with oestrogen-induced plasma LH surges in conscious control ewes. With pulses of GnRH administered every 20 min the amount of LH released was greater (P<0·05) than that in oestrogen-treated conscious control ewes. In contrast to the single surge induced by oestradiol in conscious ewes, GnRH pulses given every 20 min elicited phasic patterns of LH secretion consisting of two or three distinct surges. The failure of GnRH treatment to elicit an LH surge similar to an oestrogen-induced surge could reflect inappropriate GnRH treatment regimens, and/or inadequate priming of the pituitary with GnRH after induction of anaesthesia but before GnRH treatment. J. Endocr. (1988) 116, 143–148

IN-VITRO STUDIES OF THE EFFECTS OF OESTROGEN PRETREATMENT ON THE SENSITIVITY OF THE IMMATURE FEMALE RAT PITUITARY GLAND TO STIMULATION WITH GONADOTROPHIN RELEASING HORMONE

1977 ◽  
Vol 74 (1) ◽  
pp. 11-21 ◽  
Author(s):  
M. WILKINSON ◽  
D. DE ZIEGLER ◽  
DANIELLE CASSARD ◽  
K. B. RUF
Keyword(s):  
Pituitary Gland ◽  
Brain Lesion ◽  
Culture Technique ◽  
Female Rats ◽  
Female Rat ◽  
Immature Female ◽  
Releasing Hormone ◽  
Gonadotrophin Releasing Hormone ◽  
Unilateral Brain Lesion

The effects of oestrogen priming on the sensitivity of the anterior pituitary gland to stimulation with gonadotrophin releasing hormone (GnRH) was investigated in immature female rats using a new organ culture technique. Hemipituitary glands obtained from animals primed with a single dose of oestradiol benzoate (OB; 20 μg/100 g body weight) released significantly more LH when pulsed with GnRH (4 nmol/l) than did control hemipituitary glands. This potentiating effect was detectable as early as 5 days after birth. After a second stimulation, LH secretion remained high. These results were compared with those obtained from animals treated to induce increased levels of endogenous oestrogen on day 26 of life. Thus, hemipituitary glands were obtained from animals given two injections of OB, an injection of pregnant mare serum gonadotrophin (PMSG) or a unilateral brain lesion placed in the basal hypothalamus. Pituitary tissue was stimulated as before with a pulse of GnRH. Two injections of OB enhanced the sensitivity to stimulation. Conversely, both PMSG and lesion treatment severely reduced the sensitivity to GnRH, although PMSG-treated and lesioned animals have been used as models for the study of ovulation.

Inducing ovulation with oestradiol cypionate allows flexibility in the timing of insemination and removes the need for gonadotrophin-releasing hormone in timed AI protocols for dairy cows

2017 ◽  
Vol 29 (3) ◽  
pp. 468 ◽  
Author(s):  
R. M. Ferreira ◽  
H. Ayres ◽  
L. U. Gimenes ◽  
F. P. Torres ◽  
F. A. Lima ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Pregnancy Rates ◽  
Holstein Cows ◽  
Device Removal ◽  
Releasing Hormone ◽  
Ovulatory Follicle ◽  
Oestradiol Benzoate ◽  
Gonadotrophin Releasing Hormone

The effects of addition of gonadotrophin-releasing hormone (GnRH) to a progesterone plus oestradiol-based protocol and timing of insemination in Holstein cows treated for timed AI (TAI) were evaluated. Cows (n = 481) received a progesterone device and 2 mg oestradiol benzoate. After 8 days, the device was removed and 25 mg dinoprost was administered. Cows were allocated to one of three (Study 1; n = 57) or four (Study 2; n = 424) groups, accordingly to ovulation inducer alone (Study 1; oestradiol cypionate (EC), GnRH or both) or ovulation inducer (EC alone or combined with GnRH) and timing of insemination (48 or 54 h after device removal; Study 2). In Study 1, the diameter of the ovulatory follicle was greater for GnRH than EC. Oestrus and ovulation rates were similar regardless of ovulatory stimuli. However, time to ovulation was delayed when GnRH only was used. In Study 2, cows treated with GnRH or not had similar pregnancy per AI (P/AI) 30 days (41.5% vs 37.3%; P = 0.28) and 60 days (35.9% vs 33.0%; P = 0.61) after TAI. TAI 48 and 54 h after device removal resulted similar P/AI at 30 days (40.3% vs 38.5%; P = 0.63) and 60 days (33.8% vs 35.1%; P = 0.72). Thus, adding GnRH at TAI does not improve pregnancy rates in dairy cows receiving EC. The flexibility of time to insemination enables TAI of a large number of cows using the same protocol and splitting the time of AI.

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.

LUTEINIZING HORMONE RELEASING HORMONE-INDUCED RELEASE OF LUTEINIZING HORMONE FROM PITUITARY EXPLANTS OF COWS KILLED BEFORE OR AFTER OESTRADIOL TREATMENT

1981 ◽  
Vol 88 (1) ◽  
pp. 17-25 ◽  
Author(s):  
E. M. CONVEY ◽  
J. S. KESNER ◽  
V. PADMANABHAN ◽  
T. D. CARRUTHERS ◽  
T. W. BECK
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Lh Surge ◽  
Releasing Hormone ◽  
Oestradiol Treatment ◽  
Readily Releasable Pool ◽  
Serum Lh ◽  
Pituitary Glands ◽  
Lh Rh ◽  
Lh Releasing Hormone

In ovariectomized heifers, oestradiol decreases concentrations of LH in serum for approximately 12 h after which LH is released in a surge comparable in size and duration to the preovulatory surge. Using this model, we measured LH release induced by LH releasing hormone (LH-RH) from pituitary explants taken from ovariectomized heifers before or after an oestradiol-induced LH surge. These changes were related to changes in LH concentrations in serum and pituitary glands and hypothalamic LH-RH content. Twenty Holstein heifers were randomly assigned to one of four treatment groups to be killed 0, 6, 12, or 24 h after the injection of 500 μg oestradiol-17β. Jugular blood was collected at −2, −1 and 0 h then at intervals of 2 h until slaughter. Pituitary glands were collected and ≃2 mm3 explants were exposed to 4 ng LH-RH/ml medium for 30 min (superfusion) or 4 ng LH-RH/ml medium for 2 h in Erlenmeyer flasks. Levels of LH were measured in the medium. Hypothalami, collected at autopsy, were assayed for LH-RH content. To determine pituitary LH content, an additional 15 ovariectomized heifers were killed, five each at 0, 12 and 24 h after the injection of 500 μg oestradiol. In both groups of heifers, oestradiol reduced serum LH concentrations to ≃ 1 ng/ml, a level which persisted for 12 h, when LH was released in a surge. Pituitary sensitivity to LH-RH was increased at 6 and 12 h after the injection of oestradiol, but was markedly decreased at 24 h, i.e. after the LH surge. Despite this twofold increase in capacity of the pituitary gland to release LH in response to LH-RH, pituitary LH content did not change during 12 h after oestradiol treatment. However, LH content decreased after the LH surge and this decrease was associated with a decrease in pituitary responsiveness to LH-RH. Hypothalamic LH-RH content was not altered by these treatments. We have interpreted our results as evidence that oestradiol exerts a positive feedback effect on the pituitary gland of ovariectomized heifers such that pituitary sensitivity to LH-RH is increased twofold by the time the LH surge is initiated. In addition, oestradiol causes a transitory inhibition of LH-RH release as shown by the fact that serum LH concentrations remained low during the interval from injection of oestradiol until the beginning of the LH surge despite the fact that pituitary sensitivity to LH-RH is increased at this time. Depletion of a readily releasable pool of pituitary LH may be the mechanism by which the LH surge is terminated.

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