Inhibition of 5 alpha-reductase activity and alteration of nuclear testosterone. Dihydrotestosterone ratio in human genital skin fibroblasts.
17 beta-N, N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA) inhibits 5 alpha-reductase activity in cultured human genital skin fibroblasts. Enzyme kinetic studies analyzed by Eadie-Hofstee plots demonstrated that 4-MA is a competitive inhibitor, with an apparent Ki of 15 nM. 4-MA had a very low binding affinity for the androgen receptor. When fibroblasts were incubated in the presence of testosterone (T) and 4-MA, nuclear uptake of 5 alpha-dihydrotestosterone (DHT) decreased in parallel with the inhibition of 5 alpha-reductase activity. While the overall sum for the nuclear uptake of T and DHT diminished, the nuclear uptake of T increased. Biological androgen inactivity cannot be precluded on the basis of nuclear T plus DHT uptake.
D058891:5-alpha Reductase Inhibitors; D000328:Adult; D001378:Azasteroids / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005837:Genitalia, Male / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011944:Receptors, Androgen / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D011944:Receptors, Androgen; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; D013739:Testosterone; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D010088:Oxidoreductases