LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription
Eric Metzger, Melanie Wissmann, Na Yin, Judith M. Muller, Robert Schneider, Antoine H.F.M. Peters, Thomas Gunther, Reinhard Buettner, Roland Schule
Nature2005
Summary (paraphrased)
LSD1 (KDM1A) was known as a transcriptional corepressor that demethylates histone H3 lysine 4. The authors show it also functions as a coactivator of the androgen receptor: when complexed with AR, LSD1 demethylates repressive H3K9 marks at androgen-responsive promoters, thereby promoting AR-dependent transcription. This established histone demethylation as a direct, ligand-gated control point for androgen signaling — the same enzyme can repress or activate depending on its binding partners and histone context.
Why it’s in the systems review
The corpus's epigenetic supplement (EPI-001...015) covers DNA methylation and miRNA but has no histone-modifier entry; this landmark paper supplies the missing mechanism by which chromatin state directly gates AR output. It is the conceptual bridge for the epigenetic-persistence hypothesis: if histone-modifying enzymes set the transcriptional competence of androgen-responsive genes, then a drug-induced shift in their activity could lock in altered AR signaling after the drug is gone — exactly the kind of durable state change the Traish epigenetic model of PFS proposes.
Related records
- Video
Dr. Will Powers Interview [PFS / PAS / PSSD Summit 2026]
Dr. Will Powers · SIDEfxHUB - PFS & PSSD Patient Organisation · 21:27 (1287s)
PFS, PAS, PSSD mechanism theory; Powers' unifying model; vulnerability screening
ARARID1ACHD8HDAC10YT-iWFDBRTgT3g2026-04-29PFSPSSDPRSDCore corpus - Peer-reviewed paperPSSD Discord pick
Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution
Gauthier-Landry L, Bélanger A, Barbier O · Journal of Steroid Biochemistry and Molecular Biology
Review of two glucuronidation enzymes, UGT2B15 and UGT2B17, that convert DHT metabolites (3α-diol and androsterone) into inactive, easily excreted glucuronide conjugates. It describes how these enzymes control local androgen availability and androgen-receptor…
ARUGT2B15UGT2B17DISC-0032015 (epub 2014)PFSPSSD Discord picks - Peer-reviewed paperSIDEfxHUB pick
Immunohistochemical Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients with Persistent Sexual Side Effects after Finasteride Use for Androgenetic Alopecia
Carla Di Loreto, Francesco La Marra, Giorgio Mazzon, Emanuele Belgrano, Carlo Simone Trombetta, Sabina Cauci · PLoS ONE
In a retrospective case-control design, foreskin tissue from 8 men with persistent sexual side effects (including genital sensitivity loss) more than 6 months after stopping finasteride was compared with tissue from 11 healthy circumcision controls never…
ARLIT-0052014PFSLiterature sweep · Oct 2026