Administration of an LHRH-antagonist to male mice: effects on in vivo secretion of hormones and on the growth of a transplantable human prostatic carcinoma.
The potent luteinizing hormone releasing hormone (LHRH) antagonist [N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]-LHRH was chronically administered to male nude mice bearing the transplantable human hormone-dependent prostatic adenocarcinoma PC-82. Treatment of tumor-bearing male mice with a daily dose of 100 micrograms (4 mg/kg b w.) for 21 days did not significantly affect the growth of the PC-82 tumor tissue, or the weights of ventral prostate, seminal vesicles and testes. At 24 hours after the last dose of the antagonist the mean plasma-testosterone (T) value in these animals was not different from the control level. Administration of similar doses of the antagonist to intact normal immunocompetent male mice significantly reduced plasma LH concentrations and suppressed plasma-T to near-castrate levels, when blood was taken 2 hours after the last injection. At 24 hours after the last dose, however, plasma concentrations of LH and T had returned to control levels. This time-dependent pattern of T suppression by the antagonist was confirmed by a time-course experiment in animals receiving a single dose of the compound. These data demonstrate that a daily high dose of this antagonist cannot effectively suppress plasma-T in male mice. Therefore, the mouse may not be a suitable model for the investigation of the "castration-like" effect of LHRH-antagonists on androgen-dependent prostate xenografts.
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D005837:Genitalia, Male / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009929:Organ Size; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D013739:Testosterone / Q000097:blood*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone