Antifertility effects of a potent LH-RH antagonist in male and female rats.

The antifertility effects of the antagonistic analogue N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10-LH-RH (ORG 30276) were investigated in male and female rats. Male rats were treated with ORG 30276 at doses of 10 micrograms/kg, 100 micrograms/kg, or 1000 micrograms/kg per day for 60 days. The control rats were injected with the vehicle only. The treatment with the highest dose of the antagonist caused a significant decrease in the weights of the anterior pituitaries, testes, seminal vesicles, and ventral prostates and reduced serum and pituitary LH levels. The intermediate dose of the antagonist affected only seminal vesicle weights. The histology of the testes from the rats treated with the highest dose showed that the spermatogenesis was markedly depressed and did not advance beyond the stage of spermatocyte I; the interstitium showed cells of fibroblastic appearance. Twenty days after stopping treatment with the highest dose of the analogue there was a marked recovery of the weight of the testes, seminal vesicles, and ventral prostates. However, the animals were still infertile when caged with female rats. Sixty days after treatment the animals had recovered testicular function and fertility. The offspring were normal, with no evidence of genetic abnormalities. Female rats were injected with ORG 30276 at doses of 10 micrograms/kg, 100 micrograms/kg, or 1000 micrograms/kg per day for 14 days. The treatment with ORG 30276 did not modify body weights, but anterior pituitary and uterine weights were significantly decreased in the group of rats treated with the highest dose of the antagonist. Ovarian weights were decreased significantly in all the three groups treated with ORG 30276.(ABSTRACT TRUNCATED AT 250 WORDS

Stimulation of Release of FSH and LH by Infusion of LH-RH and Some of its Analogues

Previous studies showed that LH-releasing hormone(LH-RH) can stimulate a considerable release of FSH as well as LH in vivo if given by prolonged intravenous infusion. The effect of the duration of the infusion with synthetic LH-RH was investigated in 25-day-old male rats. LH as well as FSH was released in significant amounts after infusion with LH-RH for 30 min, and 1,2, 3, and 4 h. The release of FSH, however, did not show any dose-response relationship when LH-RH was infused for 30 min. On the other hand, if the duration of the infusion was prolonged, a dose-response relationship became apparent. The steepest dose-response curve in terms of FSH release was obtained after 4 h infusion, in the range between 25 and 200 ng of LH-RH. Two peptides (pyro)Glu-His-Trp-NH2, which is the N-terminal tripeptide of LH-RH, and (pyro)Glu-Tyr-Arg-Trp-NH2, which possesses a low degree of LH-RH activity (1 part in 7,000) but which was said to be devoid of FSH-RH activity, were also infused. (Pyro)Glu-His-Trp-NH2 did not raise LH or FSH levels in doses of 200–1,000 µg, but (pyro)Glu-Tyr-Arg-Trp-NH2 was shown to possess a definite FSH-RH activity comparable to its LH-RH activity

Luteinizing Hormone-Releasing Hormone (LH-RH) Content in the Hypothalamus of 65-Day-Old and 10-Month-Old Male Rats

The LH-releasing activity of hypothalami of 10-month-old male rats and 65-day-old male rats was investigated by their ability to raise plasma LH in ovariectomized, estrogen and progesterone-treated female rats. The results obtained indicate that the hypothalami of 10-month-old rats contain significantly more LH-RH activity than those of younger rats. The possible significance of these findings is discussed