Studies on the mechanism of the antiandrogenic effect of a putative 5 alpha-reductase inhibitor.
The mechanism of the antiandrogenic effect of 5,10-seco-19-norpregnane-4,5-diene-3,10,20-trione (secosteroid), reputedly an irreversible inhibitor of 5 alpha-reductase, was investigated. Its addition (10 microM) to culture media effectively suppressed the synthesis of rat epididymal proteins specifically induced by 0.1 microM testosterone (T) or dihydrotestosterone (DHT). Under the same conditions, secosteroid did not change the rate at which labeled T was metabolized to 5 alpha-reduced compounds. In a comparative study, secosteroid inhibited 5 alpha-reductase in an isolated microsomal fraction while not affecting the enzyme activity in minced tissue. Secosteroid was shown to be a competitor of the binding of [3H]T and [3H]DHT (both at 4 nM) to the epididymal cytosol androgen receptor, with ID50 of 1 microM for the former and 4 microM for the latter, thus explaining the mechanism involved in its antiandrogenic properties.
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003600:Cytosol / Q000378:metabolism; D003864:Depression, Chemical; D013196:Dihydrotestosterone / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009649:Norpregnadienes / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D009649:Norpregnadienes; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; C015501:(4R)-5,10-seco-19-norpregna-4,5-diene-3,10,20-trione