90 Effect of the gonadotrophin-releasing hormone antagonist on the sheep follicular population

2021 ◽  
Vol 33 (2) ◽  
pp. 152
Author(s):  
H. C. Ferreira ◽  
G. B. Vergani ◽  
J. R. Bevilaqua ◽  
N. V. Rodrigues ◽  
M. E. F. Oliveira
Keyword(s):  
Gnrh Antagonist ◽  
Population Data ◽  
Average Diameter ◽  
Placebo Treatment ◽  
Releasing Hormone ◽  
Treatment Administration ◽  
Gonadotrophin Releasing Hormone ◽  
Post Hoc ◽  
Different Doses ◽  
Synchronization Protocol

The present study was designed to study the follicular population dynamics followed or not by treatment with different doses of the GnRH antagonist in sheep. A total of 18 ewes were submitted to short-term oestrus synchronization protocol (Oliveira et al. 2009 Proc. Braz. Congr. Anim. Reprod.). The animals were 2 or 3 years old, multiparous, and had a body score of 3 to 3.5. On Day 7 after ovulation of synchronized oestrus, females were randomly divided into groups (n=6/group) according to the dose of the gonadotrophin-releasing hormone (GnRH) antagonist (Firmagon®, Ferring Pharmaceuticals) subcutaneously administered: G-control: placebo treatment (administration of saline solution); G-lower dose: 215 µg/kg; and G-higher dose: 235 µg/kg of bodyweight. B-mode ultrasound exams of the ovaries were conducted daily from 1 day before treatment with GnRH antagonist until the females showed oestrous behaviour. Ultrasound equipment (MyLab Vet®, Esaote) was used coupled to a transrectal linear transducer with a frequency of 6 and 8MHz to assess the ovarian population. Data were compared between groups, evaluation days, and their interaction by ANOVA with post hoc using Tukey’s test (P<0.05). There was no interaction (P>0.05) between the studied effects (treatments and evaluation days). The number of small follicles (2–3.49mm) was higher (P=0.0002) in the G-lower dose (5.4±0.4) compared with the G-control (4.1±0.3) and G-higher dose (3.5±0.2). The number of large follicles (≥4.5mm) was lower (P=0.01) in the G-higher dose (0.2±0.0) compared with the G-control (0.5±0.1) and G-lower dose (0.4±0.1). The number of medium follicles (3.5– 4.49mm) and the average diameter of the follicles in the 3 categories of diameter did not differ (P>0.05) between groups. The number of medium follicles differed (P=0.0131) between Days 8 and 15 after synchronized oestrus ovulation. The number of large follicles on Day 6 differed (P=0.0002) of Days 8, 9, 10, 11, 12, 16, and 17. The average diameter of medium follicles differed (P=0.0095) between Days 8 and 10. The number of small follicles and the average diameter of small and large follicles did not differ (P>0.05) between days. In conclusion, the administration of the GnRH antagonist at a higher dose in sheep suppressed the development of large tertiary or antral follicles, whereas at a lower dose, it led to an increase in the population of small follicles.

Suppression of pituitary-testis function in rats treated neonatally with a gonadotrophin-releasing hormone agonist and antagonist: acute and long-term effects

1989 ◽  
Vol 123 (1) ◽  
pp. 83-91 ◽  
Author(s):  
K.-L. Kolho ◽  
I. Huhtaniemi
Keyword(s):  
Body Weight ◽  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Long Term Effects ◽  
Adult Rats ◽  
Releasing Hormone ◽  
Serum Lh ◽  
Accessory Sex Organs ◽  
Gonadotrophin Releasing Hormone

ABSTRACT The acute and long-term effects of pituitary-testis suppression with a gonadotrophin-releasing hormone (GnRH) agonist, d-Ser(But)6des-Gly10-GnRH N-ethylamide (buserelin; 0·02, 0·1, 1·0 or 10 mg/kg body weight per day s.c.) or antagonist, N-Ac-d-Nal(2)1,d-p-Cl-Phe2,d-Trp3,d-hArg(Et2)6,d-Ala10-GnRH (RS 68439; 2 mg/kg body weight per day s.c.) were studied in male rats treated on days 1–15 of life. The animals were killed on day 16 (acute effects) or as adults (130–160 days; long-term effects). Acutely, the lowest dose of the agonist decreased pituitary FSH content and testicular LH receptors, but with increasing doses pituitary and serum LH concentrations, intratesticular testosterone content and weights of testes were also suppressed (P< 0·05–0·01). No decrease was found in serum FSH or in weights of accessory sex organs even with the highest dose of the agonist, the latter finding indicating continuing secretion of androgens. The GnRH antagonist treatment suppressed pituitary LH and FSH contents and serum LH (P< 0·05–0·01) but, as with the agonist, serum FSH remained unaltered. Testicular testosterone and testis weights were decreased (P <0·01) but testicular LH receptors remained unchanged. Moreover, the seminal vesicle and ventral prostate weights were reduced, in contrast to the effects of the agonists. Pituitary LH and FSH contents had recovered in all adult rats treated neonatally with agonist and there was no effect on serum LH and testosterone concentrations or on fertility. In contrast, in adult rats treated neonatally with antagonist, weights of testis and accessory sex organs remained decreased (P <0·01–0·05) but hormone secretion from the pituitary and testis had returned to normal except that serum FSH was increased by 80% (P <0·01). Interestingly, 90% of the antagonist-treated animals were infertile. It is concluded that treatment with a GnRH agonist during the neonatal period does not have a chronic effect on pituitary-gonadal function. In contrast, GnRH antagonist treatment neonatally permanently inhibits the development of the testis and accessory sex organs and results in infertility. Interestingly, despite the decline of pituitary FSH neonatally, neither of the GnRH analogues was able to suppress serum FSH values and this differs from the concomitant changes in LH and from the effects of similar treatments in adult rats. Journal of Endocrinology (1989) 123, 83–91

The effect of a potent gonadotrophin-releasing hormone antagonist on ovarian secretion of oestradiol, inhibin and androstenedione and the concentration of LH and FSH during the follicular phase of the sheep oestrous cycle

1990 ◽  
Vol 126 (3) ◽  
pp. 377-384 ◽  
Author(s):  
B. K. Campbell ◽  
A. S. McNeilly ◽  
H. M. Picton ◽  
D. T. Baird
Keyword(s):  
Gnrh Antagonist ◽  
Venous Blood ◽  
Hormone Secretion ◽  
Experimental Period ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Blood Samples ◽  
Releasing Hormone ◽  
Inhibitory Feedback ◽  
Gonadotrophin Releasing Hormone

ABSTRACT By selective removal and replacement of LH stimulation we sought to examine the relative importance of inhibin and oestradiol in controlling FSH secretion, and the role of LH in the control of ovarian hormone secretion, during the follicular phase of the oestrous cycle. Eight Finn–Merino ewes which had one ovary removed and the other autotransplanted to a site in the neck were given two injections of a gonadotrophin-releasing hormone (GnRH) antagonist (50 μg/kg s.c.) in the follicular phase of the cycle 27 h and 51 h after luteal regression had been induced by cloprostenol (100 μg i.m.). Four of the ewes received, in addition, i.v. injections of 2·5 μg LH at hourly intervals for 23 h from 42 to 65 h after GnRH antagonist treatment. Ovarian jugular venous blood samples were taken at 10-min intervals for 3 h before and 5 h after the injection of antagonist (24–32 h after cloprostenol) and from 49 to 53 h after antagonist (74–78 h after cloprostenol). Additional blood samples were taken at 4-h intervals between the periods of intensive blood sampling. The GnRH antagonist completely inhibited endogenous pulsatile LH secretion within 1 h of injection. This resulted in a marked decrease in the ovarian secretion of oestradiol and androstenedione (P<0·001), an effect that was reversible by injection of exogenous pulses of LH (P<0·001). The pattern of ovarian inhibin secretion was episodic, but removal or replacement of stimulation by LH had no effect on the pattern or level of inhibin secretion. Peripheral concentrations of FSH rose (P<0·01) within 20 h of administration of the antagonist and these increased levels were maintained in ewes given no exogenous LH. In ewes given LH, however, FSH levels declined within 4 h of the first LH injection and by the end of the experimental period the levels of FSH were similar to those before administration of antagonist (P<0·01). These results confirm that ovarian oestradiol and androstenedione secretion, but not inhibin secretion, is under the acute control of LH. We conclude that oestradiol, and not inhibin, is the major component of the inhibitory feedback loop controlling the pattern of FSH secretion during the follicular phase of the oestrous cycle in ewes. Journal of Endocrinology (1990) 126, 377–384

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

105 Optimization of a five-day fixed-time embryo transfer program in dairy heifers: Use of gonadotrophin-releasing hormone at initiation of the protocol

2020 ◽  
Vol 32 (2) ◽  
pp. 179
Author(s):  
R. Sala ◽  
L. Carrenho-Sala ◽  
V. Absalon-Medina ◽  
A. Lopez ◽  
M. Fosado ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Loss ◽  
Fixed Time ◽  
Transfer Program ◽  
Releasing Hormone ◽  
Utilisation Rate ◽  
Stage Embryo ◽  
Gonadotrophin Releasing Hormone ◽  
Using Data ◽  
Synchronization Protocol

Optimized fixed-time embryo transfer (FTET) protocols for synchronization of recipients have the potential to improve the overall efficiency and profitability of embryo transfer (ET) programs. The objective of the present study was to evaluate the effect of dose of gonadotrophin-releasing hormone (GnRH) at initiation of a 5-day synchronization protocol for FTET. Holstein heifers (n=2689) at two locations were synchronized using a 5-day CO-Synch protocol as follows: Day 0: CIDR inserted, Day 5: CIDR removed, prostaglandin (PG)F2α treatment (500μg cloprostenol), Day 6: PGF2α treatment, Day 8: GnRH (100μg of gonadorelin). On Day 0, at the time of CIDR insertion, heifers were assigned in a completely randomised design to the following groups: Single (a single dose of GnRH; 100μg of gonadorelin), Double (200μg of gonadorelin) or No GnRH (control). All heifers received an Estrotect patch placed on Day 5 and evaluated for signs of oestrus on Day 8. At location A, heifers were evaluated by ultrasonography 5 days after GnRH to determine presence and size of corpus luteum (CL), whereas at location B presence and location of CL were determined by transrectal palpation at the time of transfer. Heifers with a CL received an embryo 7±1 days after GnRH administration, and pregnancy was determined by ultrasonography 41 and 63 days after GnRH. Data were analysed by generalized linear mixed models. Oestrus expression was greater in heifers that received Single and Double GnRH than in the No GnRH group (P=0.001). Similarly, utilisation rate (number transferred per number treated) was greater for heifers in the Single and Double GnRH group than for those in the No GnRH group (P=0.02). Pregnancy data were analysed for a subset of recipients using data from Day 41 (n=2267) and Day 63 (n=2042). The analysis of fertility outcomes included as covariates the type of embryo (invitro fresh or frozen and invivo fresh or frozen), embryo stage, embryo quality, interval from GnRH to transfer, and oestrus expression. Pregnancies per embryo transfer (P/ET) at Days 41 and 63 were not different between treatment groups (P=0.86), and there was no interaction between type of embryo and treatment (P&gt;0.15). Pregnancy loss between Days 41 and 63 was not different (P=0.49) between treatments groups. In conclusion, the removal of the initial GnRH from a 5-day FTET protocol resulted in a slight but significant reduction in the utilisation rate and the percentage of heifers showing oestrus. However, there was no detrimental effect on fertility. As a result, the overall cost of the FTET program can be reduced by eliminating the need for the initial GnRH treatment without compromising fertility. Table 1.Reproductive performance in recipients receiving different doses of gonadotrophin-releasing hormone (GnRH) at initiation of the synchronization protocol Treatment Oestrus (n) Utilisation rate (n) P/ET1 D41 (n) P/ET D63 (n) Pregnancy loss (n) No GnRH 69.2%B (621/898) 85.0%B (763/898) 41.6% (308/740) 39.9% (268/672) 4.3% (12/280) Single GnRH 76.1%A (685/900) 88.8%A (799/900) 42.7% (329/770) 39.5% (272/689) 6.5% (19/291) Double GnRH 75.3%A (671/891) 88.7%A (790/891) 41.5% (314/757) 38.9% (265/681) 5.4% (15/280) A,BValues with different superscripts within a column differ (P&lt;0.05). 1P/ET=pregnancies per embryo transfer.

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

Sustained inhibition of sperm production and inhibin secretion induced by a gonadotrophin-releasing hormone antagonist and delayed testosterone substitution in non-human primates (Macaca fascicularis)

1989 ◽  
Vol 123 (2) ◽  
pp. 303-310 ◽  
Author(s):  
G. F. Weinbauer ◽  
S. Khurshid ◽  
U. Fingscheidt ◽  
E. Nieschlag
Keyword(s):  
Sertoli Cell ◽  
Macaca Fascicularis ◽  
Gnrh Antagonist ◽  
Cell Activity ◽  
Serum Testosterone ◽  
Sperm Production ◽  
Entire Treatment Period ◽  
Releasing Hormone ◽  
Testosterone Substitution ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Since the concomitant administration of a gonadotrophin-releasing hormone (GnRH) antagonist and testosterone suppresses sperm production only incompletely, the feasibility of treatment with a GnRH antagonist and delayed testosterone supplementation for sustained suppression of sperm production in a non-human primate model was investigated. Adult cynomolgus monkeys (Macaca fascicularis; five/group) received daily s.c. injections of the GnRH antagonist [N-acetyl-d-2-naphthyl-Ala1,d-4-chloro-Phe2,d-pyridyl-Ala3,nicotinyl-Lys5,d- nicotinyl - Lys6, isopropyl-Lys8,d-Ala10]-GnRH of either 450 or 900 μg/kg for 18 weeks. During week 6 of the GnRH antagonist treatment, all monkeys were given a single i.m. injection of 40 mg of a long-acting testosterone ester (testosterone-trans-4-n-butylcyclo-hexanecarboxylate; 20-Aet-1). Within 1 week, serum LH bioactivity was suppressed in both groups and remained low throughout the entire treatment period. Similarly, concentrations of serum testosterone declined precipitously. During week 6, substitution with testosterone restored concentrations of serum testosterone into the pretreatment range. Concentrations of serum inhibin declined within 1 week and remained suppressed during the period of treatment with the GnRH antagonist. Testicular volumes were reduced to approximately 25% of pretreatment values in both groups by week 8 and stayed in that range during the remaining period of administration of the GnRH antagonist. During the first 6 weeks of administration of the GnRH antagonist, the ejaculatory response to electrostimulation and the volume of the ejaculates diminished with time. Supplementation with testosterone during week 6 restored the ejaculatory responses within 2–3 weeks. From week 9 of GnRH antagonist treatment onwards, all monkeys given 450 μg/kg and four monkeys given 900 μg/kg produced azoospermic ejaculates. The fifth animal in the latter group became azoospermic during week 13. Azoospermia persisted throughout the entire period of treatment with the GnRH antagonist and for a further 7–13 weeks. All suppressive effects of administration of GnRH antagonist were reversible. During the recovery phase the increase in testicular volumes paralleled an increase in concentrations of serum inhibin. The suppression of inhibin levels during the period of administration of testosterone indicates that Sertoli cell activity was not restimulated by testosterone. In conclusion, GnRH antagonist treatment with delayed supplementation with testosterone might serve as a model for further research towards the development of an endocrine male contraceptive. The recovery pattern of serum levels of inhibin suggests that inhibin could serve as a marker for Sertoli cell activity. Journal of Endocrinology (1989) 123, 303–310

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.

A gonadotrophin-releasing hormone (GnRH) antagonist inhibits GnRH- but not LH-induced meiosis in follicle-enclosed rat oocytes in vitro

1982 ◽  
Vol 101 (2) ◽  
pp. 264-267 ◽  
Author(s):  
C. Ekholm ◽  
T. Hillensjö ◽  
W. J. Le Maire ◽  
C. Magnusson ◽  
C. S. Sheela Rani
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Similar Response ◽  
Releasing Hormone ◽  
Lactate Accumulation ◽  
Receptor Sites ◽  
Gonadotrophin Releasing Hormone ◽  
Stimulation Of

Abstract. Previous studies have shown that gonadotrophin-releasing hormone (GnRH) can induce resumption of meiosis in follicle-enclosed rat oocytes. In the present study a GnRH antagonistic analogue ([d-pGlul, d-Phe2,-d-Trp3,6]LRF) was found to effectively abolish the stimulatory effect of a GnRH agonist upon resumption of meiosis and lactate accumulation in isolated pre-ovulatory rat follicles but the have no effect on LH stimulation of these parameters. It is concluded that although LH and GnRH can evoke a similar response they act through separate receptor sites and that it is unlikely that GnRH mediates the effect of LH on meiosis or glycolysis.

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