Inability of continuous long-term administration of D-Nal(2)6-LHRH to abolish fertility in male rats.
A highly potent agonist of LHRH, [6-D-(2-naphthyl)-alanine]-LHRH, was administered chronically for 12 weeks to adult male rats by repetitive implantation of pellets, and its effects upon mating, fertility, and reproductive organ weights have been evaluated. Although significant declines in testicular (P less than 0.001) and epididymidal (P less than 0.001) weights were achieved, no effects on seminal vesicles, prostate, or pituitary weights were observed. After 12 weeks of continuous treatment, three of six agonist-treated rats were still successfully impregnating females. The decline in successful impregnation appeared to be related to the observed reduction in testicular spermatogenesis and in numbers of epididymal spermatozoa. The drug effects appeared reversible, as all six of the agonist-treated rats were fertile by the fifth week after cessation of treatment. Plasma levels of testosterone were markedly elevated immediately after implantation of each pellet and consistently, but not significantly, lowered during the inter-implantation periods. These observations, and the lack of effect on accessory organ weights, are consistent with the maintenance of libido in these treated rats. This is the second demonstration of a selective inhibition of spermatogenesis in the absence of a marked decline in gonadal steroidogenesis with this agent. As in the first demonstration using twice weekly injections, the degree of inhibition of spermatogenesis was insufficient to abolish fertility in the treated male rats.
D000818:Animals; D004822:Epididymis / Q000187:drug effects; D005298:Fertility / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D017274:Nafarelin; D009929:Organ Size / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011388:Prolactin; D005640:Follicle Stimulating Hormone