Treatment of 4 adult male rhesus monkeys for 8-12 months with 100-400 micrograms of a GnRH antagonist/day by means of using osmotic minipumps led to suppressed serum concentrations of LH and testosterone followed by various degrees of recovery toward pretreatment values. The serum LH response to a challenge of native GnRH was reduced by 30-75% during antagonist treatment. The serum testosterone response to GnRH was exaggerated above the response in the pretreatment period, suggesting hypersensitivity of the testis to gonadotrophin. Antagonist administration under these conditions did not alter body weight or abolish ejaculatory response. Antagonist infusion caused a 96% decrease in sperm counts. Spermatozoa recovered during the final month of antagonist treatment showed a reduced ability to penetrate denuded hamster ova. Testicular biopsies performed at the end of antagonist treatment revealed persistent spermatogenesis. However, the cellularity of the seminiferous tubules was decreased below that of pretreatment biopsies. The results of this study suggest that the amount of testosterone needed to maintain normal spermatogenesis is greater than that needed to maintain electroejaculatory response in monkeys.

In castrated male rats, a single s.c. injection of danazol has been shown to result in an inordinately prolonged inhibition of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations. In the present study, we have examined whether the same and similar routes of administration suppresses ovarian function in normally cycling rats and cynomolgus monkeys. Normally cycling female rats received danazol as a single administration either orally, i.m. or s.c. and a separate group also received danazol in silastic capsules. The duration of the dioestrous interval until the next oestrous smear was followed daily and cycle lengths were compared with vehicle-treated groups. Six normally cycling cynomolgus monkeys were followed by daily observation and blood sampling at 2-3 day intervals. After one normal cycle, danazol (200 mg/kg) was administered as a single s.c. injection. Monkeys were followed until the next menses and one cycle thereafter and blood samples were assayed for oestradiol, progesterone and bioactive LH. Oestrous cycle length in vehicle-treated control rats was 4.7 days. A single administration of danazol s.c. at the higher dose prolonged the dioestrous interval to 31.3 days (P <0.001) and a similar prolongation was observed with this high dose when administered i.m. (27.7 days; P <0.001). In normally cycling monkeys, the menstrual cycle length was 30.2 days, but following a single danazol administration, the mean duration to the next menses was prolonged to 117.5 days (P <0.001). In five out of six monkeys, there was a decrease in LH and an absence of normal oestradiol and progesterone patterns. After this prolonged hiatus, a subsequent menstrual cycle was normal in length and endocrine pattern. A single s.c. administration of danazol resulted in a prolonged suppression of ovarian cyclicity in both normally cycling rats and cynomolgus monkeys.

Adult male rats with chronic indwelling intracerebroventricular (i.c.v.) and jugular catheters were given an i.c.v. injection (over 1 min) of 1, 10, 100 ng or 1 microgram ACTH(1-24), or 300 ng ACTH(4-10) or saline, and blood samples were taken 0, 5, 15, 30 and 60 min later. Increasing dosages of ACTH(1-24) caused a dose-related rise in serum LH levels. Peak levels of serum LH (ranging from 157 to 473% of pretreatment levels) were reached 5-15 min after treatment, and then serum LH values returned to pretreatment levels by 60 min. The serum LH response to 1 microgram ACTH(1-24) did not differ from the response to 100 ng ACTH(1-24). Administration (i.c.v.) of 300 ng ACTH(4-10) was also effective in increasing serum LH values. Repeated withdrawal of blood during the experiment increased serum corticosterone values in all groups (including saline-treated), but i.c.v. administration of ACTH(1-24) or ACTH(4-10) did not further increase serum corticosterone levels. Two additional groups of rats were injected i.p. with either saline or pentobarbital (30 mg/kg body weight) 1 h before i.c.v. administration of 10 ng ACTH(1-24) and blood samples were taken as in the other groups. The animals in these groups did not show a rise in serum LH concentrations in response to ACTH(1-24). In a third experiment, rats were pretreated (i.c.v.) with either ACTH antiserum (ACTH-Ab) or normal rabbit serum 15 min before a 2-min ether stress. The ether stress evoked a significant rise in serum LH concentrations within 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of neonatal cortisol acetate administration on diurnal changes in serum corticosterone, progesterone and LH and on the response to pregnant mare serum gonadotrophin (PMSG) were examined in immature female rats. Neonatal cortisol treatment (250 micrograms/rat) abolished the diurnal rhythm of serum progesterone in rats at 27-29 days of age, and lowered overall the serum progesterone response to PMSG. Neonatal cortisol also reduced the number of animals ovulating on day 28 after PMSG injection 48 h earlier. This dosage of cortisol did not alter the diurnal rhythm of serum corticosterone in these animals. Serum LH concentrations in control rats at 27-29 days of age did not differ between 09.00 and 18.00 h, and prior treatment with cortisol acetate did not significantly influence serum concentrations of this hormone. Our data suggest that ovarian production of progesterone contributes significantly to diurnal fluctuations of this steroid in the circulation of immature rats. Perinatal exposure to cortisol acetate abolishes the diurnal rhythm of serum progesterone and impairs the ovarian response of the immature female rat to PMSG. The mechanism(s) by which cortisol acetate alters these processes remains to be determined.