Novel mechanisms of testosterone detoxification in UGT2B17 gene deletion carriers and androgen activation by gut microbiome
Abdul Basit; John Amory; Cindy Li; Vijay Mettu; Scott Heyward; Parth B. Jariwala; Matthew R. Redinbo; Bhagwat Prasad
The FASEB Journal (Experimental Biology meeting abstract)2021
Summary (paraphrased)
Proteomic comparison of human livers from UGT2B17 deletion carriers versus high expressors found upregulation of alternative steroid-metabolizing pathways (AKR1D1, AKR1C4, and related dehydrogenases/alcohol dehydrogenases) in deletion carriers, redirecting testosterone toward inactive 5beta metabolites whose glucuronidation depends on UGT2B7. Separately, incubating testosterone glucuronide with purified bacterial beta-glucuronidases and human fecal extracts showed ready but variable deconjugation back to active testosterone. The work identifies compensatory detoxification routes in deletion carriers and directly demonstrates microbial reactivation of a conjugated androgen.
Why it’s in the systems review
This is the closest published work to Powers' UGT2BXX-as-risk-modifier theorizing: it asks what the body does differently when UGT2B17 is absent and finds a metabolic rerouting strategy rather than collapse. The same study then shows the gut microbiome can undo that clearance by regenerating testosterone from its glucuronide. It belongs in the corpus because it simultaneously advances the "risk modifier" genetics angle and the gut-deconjugation angle Powers threads together.
Related records
- Powers · Reddit post
I think I have figured out at least one specific phenotype of PFS, and it is different from the "allopregnanolone" theory
u/drwillpowers · r/DrWillPowers
Powers' key genetics-first post: he proposed a specific PFS phenotype whose "base, core defect" is defective UGT2B17, disabling testosterone's main glucuronidation exit pathway. Carriers show shockingly low 3α-androstanediol glucuronide and near-zero urinary…
AKR1C1AKR1C2AKR1C3AKR1C4HSD17B2+3DWP-0032026PFSCore corpus - Powers · Reddit commentCurated Powers pick
Re: Had another random pssdpfs thought about the…
u/drwillpowers · r/DrWillPowers
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)…
ABCB1LRP2UGT2B15UGT2B17UGT2B7PRH-13982026-04-01T15:22:34ZPFSPSSDPowers Reddit history - Powers gene claim
UGT2B15; UGT2B7 — defective (minor)
Confidence: direct
Defects in these secondary glucuronidation enzymes can compound the UGT2B17 defect, further reducing testosterone exit capacity.
UGT2B15UGT2B17UGT2B7PGL-UGT2B15-UGT2B7circa May 2026PFSCore corpus