Metabolism of androgens by isolated human hair follicles

Abstract

The in vitro metabolism of [4- 14C]dehydroepiandrosterone, [7- 3]testosterone and [1,2- 3H]4-androstene-3. 17-dione was investigated in isolated male human hair follicles taken from the scalp, beard and pubic areas. The freshly plucked follicles were incubated for 5 h in KrebsRinger phosphate solution containing glucose and co-factors. Metabolites were isolated and identified by paper and thin layer chromatography, followed by crystallization to constant specific activity or isotope ratio. Testosterone was converted to androstenedione, 5α-dihydrotestosterone, 5α-androstanedione and androsterone. Formation of 5α-dihydrotestosterone was most intensive in the beard hair follicles. Androstenedione was mainly metabolized to 5α-androstanedione with limited transformation to testosterone. Dehydroepiandrosterone (DHA) was converted principally to 5-androstene-3β,17β-diol, 7α-hydroxy-DHA, androstenedione and 5α-androstanedione. Sulphoconjugation of DHA also occurred to a small extent. However, no free DHA formation was observed when scalp or beard hair follicles were incubated with tritiated DHA-S. The overall utilization of DHA by the hair follicles was far more intensive than that by human skin. The metabolism of DHA was altered in hair follicles taken from balding individuals. DHA strongly inhibited the activity of glucose-6-phosphate-dehydrogenase isolated from the hair follicles. The presence of two dihydrotestosterone-binding components was also demonstrated in the hair follicle cytosol.