Induction of chemical castration in male rats by a new long-acting LHRH-antagonist.
LHRH-antagonists might represent a useful new type of androgen deprivation to treat prostatic cancer. In this context adult intact male rats were treated subcutaneously with different concentrations of the new LHRH-antagonist antide either once (1, 3, 6, 10, 15 mg/kg) or on 5 consecutive days (5 x 3 mg/kg). The effect on serum concentration of LH and testosterone and the effect on the weights of testes, prostate, and seminal vesicles was investigated after different periods of time (24 hours, 1, 2, 3, 5, and 8 weeks). Histological evaluation of the testes was also performed. A clear dose-dependent inhibitory effect on the above-mentioned parameters was observed. The most effective treatment schedule was the single application of 15 mg/kg resulting in castration-like inhibition of prostate weights and marked inhibition of spermatogenesis within 2 weeks, which was maintained 8 weeks after the injection. Serum LH and serum testosterone concentrations were below the detection limit of the assay within 2 weeks and showed first signs of recovery after 8 weeks. Histologically, no signs indicative of irreversible effects (testes) were observed. To summarize, the LHRH-antagonist antide was found to have a profound long-lasting inhibitory but reversible effect on the reproductive system of adult intact male rats. These data emphasize the suitability of this type of compound for the treatment of prostatic cancer.
Research Laboratories of Schering AG, Berlin, Federal Republic of Germany.
U F
UF
Habenicht
M R
MR
Schneider
M F
MF
el Etreby
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000097:blood; D013997:Time Factors
D009842:Oligopeptides; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C057022:iturelix; C030741:lutrelin acetate