Regulation of the pituitary 5 alpha-reductase activity by gonadotropin releasing hormone and testosterone in the adult male rat.
Intact or castrated adult male rats were treated for nine days with GnRH (10 micrograms/day), the synthetic GnRH goserelin (100 micrograms/day) or the GnRH-antagonist Org 30276 (250 or 500 micrograms/day). In some series, 1 mg testosterone propionate was administered alone, or in combination with goserelin or Org 30276. The in vitro metabolism of [1 alpha,2 alpha-3H]testosterone by pituitary and hypothalamic homogenates was investigated in combination with the estimation of plasma concentrations of testosterone and gonadotropins. No qualitative or quantitative differences were observed in hypothalamic testosterone metabolism or in the pituitary 17 beta-hydroxysteroid dehydrogenase activity. Testosterone administration to intact male rats decreased the pituitary 5 alpha-reductase activity and LH, while administered to castrated rats, it was able to suppress totally the castration-induced increase of the 5 alpha-reductase activity and of the gonadotropin secretion. The drastic decrease of the plasma levels of testosterone, observed after a prolonged treatment with GnRH, goserelin or Org 30276 was not accompanied by an increased pituitary 5 alpha-reductase activity. Injected to castrated rats, it was observed that the castration-induced increase of the pituitary 5 alpha-reductase was further stimulated by GnRH, totally suppressed by goserelin and partially suppressed by Org 30276. Concomitant administration of goserelin or Org 30276 and testosterone propionate to castrated rats resulted in a further decrease of the pituitary 5 alpha-reductase activity, compared to the castrated, GnRH-analogue treated rats. These data indicate that the pituitary 5 alpha-reductase enzyme system is controlled by both direct steroidal and indirect GnRH-mediated mechanisms.
Vanderstichele
H
H
Laboratory of Normal and Pathological Physiology, University of Gent, Belgium.
Eechaute
W
W
Lacroix
E
E
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002064:Buserelin / Q000031:analogs & derivatives / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D017273:Goserelin; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009919:Orchiectomy; D010902:Pituitary Gland / Q000201:enzymology*; D010906:Pituitary Hormone-Releasing Hormones / Q000097:blood / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D010906:Pituitary Hormone-Releasing Hormones; D011422:Propionates; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C029658:propionic acid; D002064:Buserelin