UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 enzymes are major determinants of the androgen response
Sarah Chouinard; Olivier Barbier; Alain Bélanger
Journal of Biological Chemistry2007
Summary (paraphrased)
The UGT2B15 and UGT2B17 enzymes conjugate dihydrotestosterone and its metabolites androstane-3α,17β-diol and androsterone. Both enzymes are present in epithelial cells of the human prostate, where significant concentrations of the corresponding glucuronides were detected. Using RNA interference in the androgen-dependent LNCaP cell line, the authors showed that knocking down these two enzymes markedly alters androgen inactivation, establishing them as major determinants of local androgen termination.
Why it’s in the corpus
names the enzymes whose deficiency would produce androsterone buildup
Why it’s in the systems review
This is the clearance-focused core of the axis: it identifies the exact enzymes (UGT2B15/UGT2B17) that terminate androsterone signaling by glucuronidation, which is precisely the pathway Powers theorizes is defective in the buildup model (and the gene family of his hypothesized UGT2B17 "risk modifier" deletion). It makes the mechanistic chain explicit — defective UGT2B17 → reduced androsterone glucuronidation → androsterone accumulation — and gives the treatment-candidate search a concrete enzymatic target. Classification is "steroid clearance / glucuronidation" because the paper is about termination of signaling, not systemic hormone levels.
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Reply to a community member's glucuronidation-theory thought about sulfation labs. Powers notes the discussed factor interacts with androgen production and ABCC-family transporters (he believes ABCB1 specifically, with the caveat that he read it long ago)…
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