Dehydroepiandrosterone and dehydroepiandrosterone sulfate metabolism in human genital skin

Genital skin samples were obtained from normal women and men to determine the extent of conversion of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT) and other androgen metabolites and to assess sulfatase activity. The skin samples were minced and incubated with 3H-DHEA or 3H-dehydroepiandrosterone sulfate (3H-DHEAS) in medium for 1 hour at 37 degrees C. The following metabolites of DHEA were isolated after extraction and chromatography: 5-androstene-3 beta,17 beta-diol (delta 5-diol), 5 alpha-androstane-3,17-dione (5 alpha-delta 4A), testosterone, DHT, androsterone (A), and 5 alpha-androstane-3 alpha,17 beta-diol. Although the conversion of DHEA to all the metabolites was low, the conversions were higher in men than in women. In women, conversions of DHEA to delta 5-diol and androstenedione (delta 4A) were highest, followed by conversions of DHEA to DHT and 5 alpha-delta 4A, whereas in men the formation of delta 4A and 5 alpha-delta 4A was highest, followed by delta 5-diol and A. There was a significant conversion of DHEAS to DHEA in both women and men, although the sulfatase activity was approximately six times higher in men. We conclude that despite the low conversion of DHEA to DHT, significant androgenecity may result from pathological levels of DHEAS.