METABOLISM OF 5-ALPHA-ANDROSTANE-3-BETA,17-BETA-DIOL IN BALD AND HAIRY AREAS OF THE SCALP

In androgen target tissues, testosterone undergoes extensive biotransf ormation to 5 alpha-dihydrotestosterone which in turn is metabolized i nto 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 b eta,17 beta-diol. From studies mainly in the prostate, it has been sho wn that 5 alpha-androstane-3 beta,17 beta-diol can be further converte d to 5 alpha-androstane-3 beta,6 alpha(beta)/7 alpha(beta), 17 beta-tr iols. The present studies show that among the metabolites of 5 alpha-a ndrostane-3 beta,17 beta-diol in scalp homogenates, three were isolate d by thin-layer chromatography and identified against standard steroid s: 5 alpha-dihydrotestosterone, epiandrosterone, and 5 alpha-androstan edione. Another peak was observed near the origin with a greater polar ity than 5 alpha-androstane-3 beta,17 beta-diol. The chromatograms obt ained by incubating 5 alpha-androstane-3 beta,17 beta-diol with scalp and prostate homogenates are similar, and it is known that the polar m etabolites in the prostate are 5 alpha-androstane-3 beta,6 alpha(beta) /7 alpha(beta),1 7 beta-triols, suggesting that these steroids are for med in both tissues. In addition, the similarity of chromatograms and mass spectra, obtained when 3 beta-diol polar metabolite(s) and authen tic 5 alpha-androstane-3 beta,7 beta,17 beta-triol were subjected to G C/MS, confirms this hypothesis. The dependence of the formation of pol ar metabolites on the substrate (5 alpha-androstane-3 beta,17 beta-dio l) concentration (50 nM-1.3 mu M) was studied and resulted in saturati on and linear Lineweaver plots from both bald and hairy areas of the s calp. The mean Michaelis constant (K-m) was 1 mu M for both areas, and the maximal metabolic rates (V-max) were 10.9 +/- 6.2 pmol/mg protein /h (n = 9) in bald scalp and 8.2 +/- 0.1 pmol/mg protein/h (n = 3) in hairy scalp. The other metabolic rates of formation were: 25.8 +/- 19. 5-38.4 +/- 17.9 pmol/mg protein/h for epiandrosterone, 45.8 +/- 40.9-8 .4 +/- 2.2 pmol/mg protein/h for 5 alpha-dihydrotestosterone, and 8.3 +/- 2.6-9.2 +/- 1.0 pmol/mg protein/h for androstanedione in bald and hairy scalp, respectively. As 5 alpha-androstane-3 beta,6 alpha(beta)/ 7 alpha(beta), 17 beta-triols do not possess androgenic properties, th ey are generally considered to be final metabolites, so that their pro duction rate could be an important factor controlling the amount of 5 alpha-androstane-3 beta,17 beta-diol inside the target cell.