The roles of inhibin and gonadotrophin-releasing hormone in the control of gonadotrophin secretion in the ewe

1986 ◽  
Vol 111 (2) ◽  
pp. 287-296 ◽  
Author(s):  
G. B. Martin ◽  
J. M. Wallace ◽  
P. L. Taylor ◽  
H. M. Fraser ◽  
C. G. Tsonis ◽  
...  
Keyword(s):  
Initial Response ◽  
Hypothalamic Stimulation ◽  
Gnrh Analogue ◽  
Relative Importance ◽  
Rapid Rise ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Differential Control

ABSTRACT The respective roles and relative importance of ovarian inhibition and hypothalamic stimulation in the differential control of the secretion of FSH and LH were studied in the ewe. In the first experiment two groups of ten intact ewes were injected i.v. twice daily with 9 ml charcoal-extracted bovine follicular fluid (bFF), a preparation rich in inhibin (3·65 ku./ml), throughout the luteal phase of the oestrous cycle. Compared with the control ewes, this treatment significantly reduced pituitary and plasma FSH concentrations and increased the frequency and amplitude of the LH pulses, but did not affect pituitary LH concentrations. In a second experiment, five control and five bFF-treated ewes from experiment 1 were ovariectomized and the injection regime was altered to 2·5 ml s.c. every 8 h. This treatment was maintained for 21 days. In control ewes, plasma FSH concentrations rose significantly within 12 h and continued to rise for 3–4 days. Treatment with bFF abolished this increase and maintained plasma FSH concentrations below those observed in intact ewes. The rise in mean plasma LH concentrations evoked by ovariectomy was also partially inhibited in the bFF-treated ewes. The response to the gonadotrophin-releasing hormone (GnRH) agonist buserelin (5 μg i.v.) was measured 6, 12 and 18 days after ovariectomy. In control ewes the agonist consistently evoked large surges of both hormones but in bFF-treated ewes the FSH response was completely blocked and the initial phase of the LH response (the first 'pool') was greatly reduced. In experiment 3, six ewes were ovariectomized and passively immunized against GnRH 3 days after oestrus. The increase in plasma LH which normally follows ovariectomy was completely abolished and mean concentrations remained very low and did not change over the following 14 days. In contrast, mean FSH concentrations rose significantly within 12 h of ovariectomy and continued to rise until the third day, after which they fell gradually. Treating three of the ewes with bFF (2·5 ml s.c. every 8 h) 8 days after ovariectomy and immunization further reduced the FSH concentrations. When the ewes were injected repeatedly (200 ng i.v., hourly for 5 h) with [d - penicillamine - (But)6] - GnRH(1–9)nonapeptide ethylamide, a synthetic GnRH analogue which does not bind to the antiserum, there was a rapid rise in the secretion of LH in both control and bFF-treated animals but, as with the responses to buserelin, the initial response was significantly lower in bFF-treated than in control ewes. The concentrations of FSH rose after each injection in the control ewes but showed only a small response after the fourth and fifth injections in the bFF-treated ewes. We conclude that bFF completely blocks the secretion of FSH in the acutely ovariectomized ewe by blocking the pituitary response to GnRH, an effect which is probably mediated, at least in part, by a reduction in the concentration of FSH in the gonadotrophs. The release of LH was only partially inhibited by bFF treatment and this effect was not related to pituitary LH concentrations. It seems that LH release is acutely controlled by hypothalamic stimulation and chronically controlled by ovarian feedback at the pituitary level whereas FSH release is controlled chronically by changes in hypothalamic stimulation and acutely by ovarian feedback on the anterior pituitary gland. Inhibin is an important component of this feedback on FSH release. J. Endocr. (1986) 111, 287–296

Effects of modifiers of cytoskeletal structures on the dynamics of release of LH from sheep anterior pituitary cells stimulated with gonadotrophin-releasing hormone, K+ or phorbol ester

1987 ◽  
Vol 112 (2) ◽  
pp. 289-298 ◽  
Author(s):  
R. P. McIntosh ◽  
J. E. A. McIntosh ◽  
L. Starling
Keyword(s):  
Initial Response ◽  
Cytochalasin D ◽  
Receptor Interaction ◽  
Release Mechanism ◽  
Pituitary Cells ◽  
Short Term ◽  
Releasing Hormone ◽  
Cell Components ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT This study investigated the importance of reorganization of cell components by cytoskeletal structures to the short-term dynamic changes in LH release from dispersed sheep pituitary cells in perifusion, when stimulated with different dynamic patterns of gonadotrophin-releasing hormone (GnRH). The changes in rate of LH release investigated were the initial response to GnRH, desensitization, change of dose–response during desensitization, and recovery of sensitivity between pulses of stimulation. Cytochalasin D and colchicine were used to modify microfilament and microtubule action respectively. To determine whether receptor movement after binding of agonist was involved in the altered responses, K+ and phorbol 12-myristate 13-acetate (PMA) were used as stimulants because they cause LH release independently of agonist-receptor interaction. After 3 and 48 h culture on dextran beads and 2–3 h incubation in the presence and absence of 2–48 μmol cytochalasin D/l, or 8 or 250 μmol colchicine/l, aliquots of collagenase-dispersed sheep pituitary cells were stimulated at 37 °C in tubes or in a multicolumn perifusion system with 850 pmol GnRH/l, 109 mmol K+/l or 10 nmol PMA/l. Fractions of supernatant or effluent were collected at intervals and LH concentrations measured by radioimmunoassay. Control samples were treated in the same way but without stimulation. Maximal, reversible enhancement of LH release over the first 20 min following stimulation with all secretogogues was observed after incubation of cells in 6 μmol cytochalasin/l. Desensitization behaviour, the supramaximal response, and the ability of cells to recover sensitivity to repeated pulses of GnRH were not altered by this modifier of microfilament polymerization at 6 or 24 μmol/ml. Colchicine at 8 μmol/l caused no changes in LH release. At 250 μmol/l, colchicine reduced the initial response of cells to GnRH stimulation but its action at this relatively high level may not be specific; there was no other major change in desensitization patterns, nor recovery of sensitivity to pulsed GnRH stimulation. Each treatment affected cellular responses similarly before and after culture. From studying the details of the dynamics of the short-term responses of gonadotrophs, we conclude that transport of cell components involving microfilaments and microtubules is unlikely to be a major limitation on the rate of LH release during desensitization, the supramaximal response, or the recovery of sensitivity between pulses of GnRH. This suggests that biochemical reactions rather than physical translocation may be rate-limiting in these processes. In addition, although inhibition of microfilament action does appear to enhance the earliest observed response to stimulation of the LH-release mechanism, this occurs after protein kinase C activation and is probably not related to impairment of processes such as polymerization and sequestration of agonist-bound GnRH receptors because the effects are also observed with K+ and PMA, stimulants acting independently of agonist-receptor interaction. J. Endocr. (1987) 112, 289–298

THE EFFECT OF CYPROTERONE ACETATE ON THE PLASMA GONADOTROPHIN RESPONSE TO GONADOTROPHIN RELEASING HORMONE

1976 ◽  
Vol 81 (3) ◽  
pp. 680-684 ◽  
Author(s):  
Richard A. Donald ◽  
Eric A. Espiner ◽  
R. John Cowles ◽  
Joy E. Fazackerley
Keyword(s):  
Testosterone Level ◽  
Cyproterone Acetate ◽  
Luteinising Hormone ◽  
Follicle Stimulating Hormone ◽  
Plasma Testosterone ◽  
Plasma Testosterone Level ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Male Patients

ABSTRACT Cyproterone acetate (100–150 mg daily) was administered to 8 male patients with excessive libido. Within 3 months a significant fall (P < 0.02) in plasma testosterone was demonstrated. The plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotrophin releasing hormone (LH/FSH-RH) were also significantly impaired (P < 0.05). A direct correlation between the resting plasma testosterone level and the LH response to LH/FSH-RH was demonstrated (r = 0.743). It is concluded that the fall in plasma testosterone levels in patients receiving cyproterone acetate may be attributed to suppression of LH release, rather than an antiandrogen effect on the testis or hypothalamus.

Effect of basal and pulsatile LH release on FSH-stimulated follicle growth in ewes chronically treated with gonadotrophin-releasing hormone agonist

1991 ◽  
Vol 128 (3) ◽  
pp. 449-456 ◽  
Author(s):  
H. M. Picton ◽  
A. S. McNeilly
Keyword(s):  
Gnrh Agonist ◽  
Follicular Development ◽  
Follicle Growth ◽  
Releasing Hormone ◽  
Normal Number ◽  
Stage Of Development ◽  
Normal Diameter ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Follicular Response

ABSTRACT Ewes chronically treated with gonadotrophin-releasing hormone (GnRH) agonist were used to investigate the importance of the peripheral concentration of LH in FSH-stimulated follicular development. Twenty-four Welsh Mountain ewes were treated with two agonist implants containing 3·3 mg buserelin. During week 6 of treatment all the ewes were given a 72-h continuous infusion of ovine FSH alone (3 μg/h) or FSH with large (7·5 μg)- or small (2·5 μg) amplitude pulses of ovine LH delivered at 4-hourly intervals. The importance of baseline LH throughout the FSH infusion was evaluated in six animals which were treated with a specific antiserum against bovine LH (LH-AS) 15–20 h before the start of FSH treatment. In the absence of LH-AS, infusion of FSH alone or with large or small pulses of LH stimulated the development of a normal number of small follicles (≤ 2·5 mm in diameter) and large follicles (> 2·5 mm in diameter). These follicles had normal diameter and steroid secretion compared with control ewes on day 8 of the luteal phase. In contrast, the animals pretreated with LH-AS developed no follicles > 2·0 mm in diameter but the number of small follicles per ewe was significantly (P < 0·05) increased. These results support the hypothesis that FSH in the absence of pulsatile LH release stimulates preovulatory follicular development in ewes treated with GnRH agonist. The follicular response to LH pulses of different amplitude is dependent on both the stage of development of the follicle and the peripheral concentration of FSH. The endogenous basal level of LH present throughout the FSH infusion is essential for FSH to induce follicle growth beyond > 2·5 mm in diameter. Journal of Endocrinology (1991) 128, 449–456

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

Gonadotrophin releasing hormone receptor regulation in relationship to gonadotrophin secretion

1985 ◽  
Vol 23 (5) ◽  
pp. 691-702 ◽  
Author(s):  
R.N. Clayton ◽  
A. Detta ◽  
S.I. Naik ◽  
L.S. Young ◽  
H.M. Charlton
Keyword(s):  
Hormone Receptor ◽  
Receptor Regulation ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone

Pituitary and testicular responses in sexually mature bulls after intravenous injections of graded doses of LH-releasing hormone

1984 ◽  
Vol 103 (3) ◽  
pp. 371-376 ◽  
Author(s):  
M. J. D'Occhio ◽  
B. P. Setchell
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Anterior Pituitary Gland ◽  
Limiting Factor ◽  
Releasing Hormone ◽  
Intravenous Injections ◽  
Gonadotrophin Secretion ◽  
Lh Release ◽  
Lh Releasing Hormone ◽  
Sexually Mature

ABSTRACT The capacity of the anterior pituitary gland and testes in mature bulls (705±9 (s.e.m.) kg body wt, n = 4) to respond to graded doses of LH-releasing hormone (LHRH) was assessed relative to endogenous profiles of LH and testosterone secretion. Endogenous hormone profiles were determined by bleeding bulls at 20-min intervals for 12 h. Responses to LHRH were assessed on successive days after single intravenous injections of 1, 5, 10, 50 or 100 ng LHRH/kg body wt. Blood samples were taken at −40, −20, 0, 10, 20, 30, 40, 60 and 120 min relative to LHRH injection. During a 12-h bleed bulls showed spontaneous pulses of LH and testosterone which had peak amplitudes of 2·6±0·5 μg/l and 44·5 ± 7·1 nmol/l respectively. Respective peak LH (μg/l) and testosterone (nmol/l) responses to LVRH were as follows: 1 ng LHRH (3·0±0·7: 47·3±4·1); 5 ng LHRH (8·0±1·2; 52·8 ± 6·2); 10 ng LHRH (11·1±2·3; 57·7 ± 9·1); 50 ng LHRH (19·2±2·8; 47·9±8·6); 100 ng LHRH (19·1±4·7; 43·9 ±6·4). A dose of 1 ng LHRH/kg produced LH and testosterone responses which were comparable in amplitude to spontaneous peaks in the respective hormone. There was a linear (y = 0·28x+5·72; r = 0·81) increase in the LH response to doses of LVRH between 1 and 50 ng/kg; corresponding testosterone responses showed no relationship with the dose of LHRH. The capacity of the anterior pituitary gland to release amounts of LH eight to ten times in excess of those secreted during spontaneous peaks suggests that (1) there exists a large releasable store of LH in the anterior pituitary gland and (2) hypothalamic LHRH is a limiting factor in gonadotrophin secretion. In contrast to LH release, the androgenic response of the testes to acute gonadotrophic stimulation is determined largely by prevailing steroidogenic activity. J. Endocr. (1984) 103, 371–376

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

Effects of crude and highly purified bovine inhibin (Mr 32 000 form) on gonadotrophin production by ovine pituitary cells in vitro: inhibin enhances gonadotrophin-releasing hormone-induced release of LH

1990 ◽  
Vol 127 (1) ◽  
pp. 149-159 ◽  
Author(s):  
S. Muttukrishna ◽  
P. G. Knight
Keyword(s):  
Primary Cultures ◽  
Suppressive Effect ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Α Subunit ◽  
Releasing Hormone ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Primary cultures of ovine pituitary cells (from adult ewes) were used to investigate the actions of steroid-free bovine follicular fluid (bFF) and highly-purified Mr 32 000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of each hormone were also determined allowing total gonadotrophin content/well to be calculated. As in rats, both crude and highly purified inhibin preparations promoted a dose (P < 0·001)- and time (P < 0·001)-dependent suppression of basal and GnRH-induced release of FSH as well as an inhibition of FSH synthesis, reflected by a fall in total FSH content/well. However, while neither inhibin preparation affected basal release of LH or total LH content/well, GnRH-induced LH release was significantly (P< 0·001) increased by the presence of either bFF (+ 75%) or highly-purified inhibin (+ 64%) in a dose- and time-dependent manner. This unexpected action of bFF on GnRH-induced LH release was abolished in the presence of 5 μl specific anti-inhibin serum, confirming that the response was indeed mediated by inhibin. Furthermore, neither oestradiol-17β (1 pmol/l–10 nmol/l) nor monomeric α-subunit of bovine inhibin (2·5–40 ng/ml) significantly affected basal or GnRH-induced release of LH. These in-vitro findings for the ewe lend support to a number of recent in-vivo observations and indicate that, in addition to its well-documented suppressive effect on the synthesis and secretion of FSH, inhibin may actually facilitate LH release in this species, in marked contrast to its action in the rat. Journal of Endocrinology (1990) 127, 149–159

scholarly journals Regulation of gonadotrophin secretion by inhibin, testosterone and gonadotrophin-releasing hormone in pituitary cell cultures of male monkeys

1998 ◽  
Vol 159 (1) ◽  
pp. 103-110 ◽  
Author(s):  
U Fingscheidt ◽  
GF Weinbauer ◽  
HL Fehm ◽  
E Nieschlag
Keyword(s):  
Dose Response ◽  
Pituitary Cells ◽  
Basal Secretion ◽  
Response Curves ◽  
Gonadotrophin Secretion ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone ◽  
Dose Response Curves ◽  
Male Rhesus

The effects of bovine inhibin, testosterone and GnRH on gonadotrophin secretion by primate pituitary cells were characterized in vitro using pituitaries from six male rhesus monkeys and one male cynomolgus monkey. The effect of inhibin on basal secretion of FSH and LH was investigated. Dose-response curves in monkeys and rats were compared. GnRH dose-response curves in the presence and absence of testosterone were also examined in monkeys. In monkey pituitary cells, testosterone at a concentration of 10(-7) M had no effect on LH or FSH secretion. Inhibin suppressed FSH secretion to 50.8% of that of controls with no effect on LH. In rats, FSH secretion was suppressed to 45.0% of that of controls with a median effective dose (ED50, 95% range) of 1.298 (1.064-1.584) U/ml, compared with 1.024 (0.7204-1.455) U/ml in monkeys. In monkey pituitary cells, LH release was stimulated 9.9-fold and FSH 3.3-fold by GnRH. Testosterone had no effect on basal or GnRH-stimulated gonadotrophin release. These results support the view that the pituitary is not the target organ for the negative feedback action of testosterone in the male. In vitro, inhibin is the major regulator of FSH secretion at the pituitary level.

Effect of gonadotrophin-releasing hormone analogue (GnRH-A) administration on serum gonadotrophin and steroid levels in patients with polycystic ovarian disease

1986 ◽  
Vol 111 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Alessandro Mongioi ◽  
Grazia Maugeri ◽  
Maria Macchi ◽  
Aldo Calogero ◽  
Enzo Vicari ◽  
...  
Keyword(s):  
Marked Decrease ◽  
Close Correlation ◽  
Gnrh Analogue ◽  
Hormone Analogue ◽  
Polycystic Ovarian Disease ◽  
Releasing Hormone ◽  
Ovarian Disease ◽  
Serum Lh ◽  
End Of Treatment ◽  
Gonadotrophin Releasing Hormone

Abstract. A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 μg was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P < 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4. 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P < 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P <0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.

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