Suppression of spermatogenesis in a nonhuman primate (Macaca fascicularis) by concomitant gonadotropin-releasing hormone antagonist and testosterone treatment

1987 ◽  
Vol 114 (1) ◽  
pp. 138-146 ◽  
Author(s):  
G. F. Weinbauer ◽  
F. J. Surmann ◽  
E. Nieschlag
Keyword(s):  
Macaca Fascicularis ◽  
Gnrh Antagonist ◽  
Gonadotropin Releasing Hormone ◽  
Serum Concentrations ◽  
Sperm Production ◽  
Cynomolgus Monkeys ◽  
Releasing Hormone ◽  
Testicular Regression ◽  
Pre Treatment ◽  
Testicular Histology

Abstract. The effects of concomitant testosterone (T)-supplementation on gonadotropin-releasing hormone (GnRH) antagonist-induced testicular regression in cynomolgus monkeys (M. fascicularis) were investigated. Four adult monkeys were infused via osmotic minipumps with daily amounts of 2 mg of a potent GnRH antagonist (N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg (Et2)6, D-Ala10)-GnRH (RS-68439) for a period of 104 days. Androgen substitution was provided via T-filled Silastic capsules implanted at initiation of GnRH antagonist treatment. Within 1–4 days of GnRH antagonist administration, serum concentrations of bioactive LH became undetectable. The implants maintained serum T at 50–80% of pre-treatment levels. Sperm production decreased in three out of four monkeys. One animal became azoospermic by the 13th week of treatment and the ejaculates of two other monkeys contained less than 5 × 106 sperm. In the fourth monkey, spermatogenesis was less affected. Testicular histology, judging from biopsies at termination of GnRH antagonist treatment, was typical of the hypogonadotropic status in 3 of the 4 monkeys. The most affected tubules contained only spermatogonia and Sertoli cells. Although comparison with GnRH antagonist treatment alone in a previous study indicated a delay of spermatogenic inhibition with testosterone, the present study confirms the potential of GnRH antagonist for male fertility regulation.

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

Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone antagonist-treated male rats

1995 ◽  
Vol 132 (3) ◽  
pp. 357-362 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
E Aguilar
Keyword(s):  
Gnrh Antagonist ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Gonadotropin Releasing Hormone ◽  
Male Rats ◽  
Gonadotropin Secretion ◽  
Releasing Hormone ◽  
Treated Male ◽  
Lh Secretion ◽  
Stimulating Hormone

Tena-Sempere M, Pinilla L, Aguilar E. Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone agonist-treated male rats. Eur J Endocrinol 1995;132: 357–62. ISSN 0804–4643 The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-d-pClPhe-d-pClPhe-d-TrpSer-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic–pituitary axis in controlling LH and FSH secretion. Manuel Tena-Sempere, Department of Physiology, Faculty of Medicine, University of Córdoba, 14004 Córdoba, Spain

103 Hormonal stimulation and post-breeding sperm induction in the mountain yellow-legged frog, Rana muscosa

2019 ◽  
Vol 31 (1) ◽  
pp. 177 ◽  
Author(s):  
N. Calatayud ◽  
M. Curtis ◽  
B. Durrant
Keyword(s):  
Sperm Concentration ◽  
Gonadotropin Releasing Hormone ◽  
Breeding Period ◽  
Sperm Production ◽  
Hormonal Stimulation ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Effective Manner ◽  
First Choice ◽  
Different Doses

The first choice of any captive animal program should be to promote natural breeding through appropriate diet and environmental conditions. However, in cases of poor reproductive performance, the administration of exogenous hormones can induce breeding behaviours and gamete release. Part of the approach to the Mountain yellow-legged frog recovery program is the collection of sperm for cryobanking as a means of preserving genetic diversity in a cost- and space-effective manner. To develop a protocol for induction of sperm release from Mountain yellow-legged frogs, we tested the administration of gonadotropin-releasing hormone agonist (d-Ala6, des-Gly10 ethylamide LHRH derivative) and hCG singly or in combination. Once a month, animals were injected with a single dose of saline amphibian ringers (control) or 1 of 10 hormone treatments. Groups 1-4 received a single intraperitoneal injection of gonadotropin-releasing hormone agonist administered in 4 different doses: (1) 0.3 μg/g body weight (bw); (2) 0.4 μg/g bw; (3) 0.6 μg/g bw; and (4) 1 μg/g bw. Groups 5 and 6 were injected with 5 and 10IU hCG/g bw, respectively, and groups 7-10 received a combined injection of hCG and GnRH in four different doses: (7) 5 IU/g hCG with 0.3 μg/g GnRH; (8) 10 IU/g hCG with 0.3 μg/g GnRH; (9) 5 IU/g hCG and 0.6 μg/g GnRH; and (10) 10 IU/g hCG and 0.6 μg/g GnRH. Hormone treatments began in July 2015, 2 months after the end of the breeding season to allow males a post-breeding recovery time. Monthly administration continued from July until December 2015, ending before the brumation period. In 2016, treatments resumed again in July, after another breeding period. In 2017, hormone treatments began in April, during the reproductive season, and continued until July. From July 2015 through November 2016, sperm concentration and motility were examined in response to hormones treatment groups 1, 3, 5, 6, and 7-10. In April 2017, based on previous results, experiments were redesigned to include group 9 from 2015-16, and two new groups, 2 and 4. Spermiation was not easily hormonally induced when administered from August-October 2015, August-September 2016, and in July 2017. These low-response periods coincided with post-breeding months when only 3.7% (3/81) of males responded to either 10 IU/g hCG, 0.6 μg/g GnRH, or a combination of 5 IU/g hCG and 0.6 μg/g GnRH. Sperm production was significantly affected (P<0.05) by the month of hormone administration and hormone treatments during the responsive periods (P<0.0001) of April-June and October-November. However, hormone doses and treatments had no significant effect on the average or total sperm concentration per male (P<0.05). Motility and speed of forward progression were not significantly affected by treatment (P<0.05). This study demonstrates the seasonality of sperm production in this species, which may be attributed to testicular recrudescence during the summer months following breeding. Without hormonal stimulation, spermiation did not occur during the nonreproductive part of the year.

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