17-n-n-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one and epostane

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.

Topics: Adult; Aged; Androstenols; Azasteroids; Cyproterone Acetate; Dehydroepiandrosterone; Dihydrotestosterone; Enzyme Inhibitors; Female; Humans; In Vitro Techniques; Kinetics; Male; Middle Aged; Multienzyme Complexes; Progesterone Reductase; Skin; Steroid Isomerases; Steroids