INHIBITION OF TESTOSTERONE 5α-REDUCTASE BY AND ANTIANDROGENICITY OF ALLENIC 3-KETO-5,10-SECOSTEROIDS

Publisher Website
Google Scholar
Abstract
(4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione(II), a 3-keto-5,10-secosteroid which is an irreversible inhibitor of .DELTA.5-3-ketosteroid isomerase was tested for its possible antiandrogenicity in the hamster flank organ test. The organs of female animals topically treated with 4 .mu.g of testosterone propionate (TP) for 4 wk enlarged in size and showed pigmentation resembling adult males. When compound II was applied concomitantly with TP, androgenic stimulation was completely blocked and the flank organs remained small like those of female animals. Compound II may be a useful anti-androgen when applied topically. It may act mainly by inhibition of the formation of 5.alpha.-reduced metabolites of testosterone, as judged by its effect on rat prostatic 5.alpha.-reductase. Thus, incubation of a rat prostatic homogenate with [4-14C]testosterone produced 5.alpha.-dihydrotestosterone and 5.alpha.-androstane-3.alpha.,17.beta.-diol as the main products. When compound II was included in the incubation mixture, the production of these 5.alpha.-reduced metabolites was markedly inhibited.

This publication has 1 reference indexed in Scilit: