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)
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000097:blood; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone