Activity and inhibition of 3-beta-hydroxysteroid dehydrogenase/delta-5-4-isomerase in human skin.
Activity and inhibition of 3 beta-hydroxysteroid dehydrogenase/delta 5-4-isomerase, a key example of biosynthesis of androgenic steroids, in human skin were studied. Whole-width dermal tissue specimens excised from various regions of the male and female body were investigated with an in vitro radioenzyme assay method using dehydroepiandrosterone as substrate. The Michaelis-Menten constant of the enzyme was found to be Km = 10nM and the maximal velocity was Vmax = 0.625 pmol produced 4-androstene-3,17-dione/mg protein/20 min. Activity of 3 beta-hydroxysteroid dehydrogenase/delta 5-4-isomerase in male inguinal skin (n = 8) was 0.132-0.412, in female abdominal skin (n = 4) 0.140-0.255, in perineal skin (n = 4) 0.138-0.962 pmol/mg protein/20 min. The synthetic steroids cyproterone acetate, 4-MA and epostane proved to be potent inhibitors, IC50 values were 150, 6.2 and 1.45 nM, respectively.
Tóth
I
I
Endocrine Unit, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Szécsi
M
M
Julesz
J
J
Faredin
I
I
D000328:Adult; D000368:Aged; D000737:Androstenols / Q000494:pharmacology; D001378:Azasteroids / Q000494:pharmacology; D017373:Cyproterone Acetate / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012867:Skin / Q000201:enzymology*; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D000737:Androstenols; D001378:Azasteroids; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D013256:Steroids; D013196:Dihydrotestosterone; D003687:Dehydroepiandrosterone; D017373:Cyproterone Acetate; C046855:epostane; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D011375:Progesterone Reductase; D013251:Steroid Isomerases