Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium

humans, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD, and 5alpha-reductase enzymes convert dehydroepiandrosterone (DHEA), androstenedione, and testosterone into the most potent natural androgen dihydrotestosterone (DHT) in the prostate. This androgen is transformed mainly in situ to two Phase I metabolites, androsterone (ADT) and androstane-3alpha,17beta-diol (3alpha-DIOL), which can, however, be back-converted to DHT. Here, we report recent findings on the characterization of specific anti-UDP-glucuronosyltransferases (UGT)2BI5 and 21317 antibodies and their use to identify UGT2B expressing-cells in the human prostate epithelium. We found that UGT2B 17 is expressed in basal cells where DHEA is convened into 3a-DIOL and ADT. By contrast, the expression of UGT2B 15 was observed only in luminal cells, where DHT is formed from testosterone. These results demonstrate that, in the human prostate, UGT2B15 and UGT2B17 genes have complementary roles, and are expressed in cells where their specific substrates are synthesized. This reinforces the hypothesis that UGT enzymes catalyze an important mechanism for modulating the action of steroids and protecting the steroid-sensitive tissues from deleteriously high steroid concentrations.