AR
androgen receptor
Named by Dr Will Powers
Gene summary
A protein-coding gene on chromosome X (steroid and nuclear hormone receptors). The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor.
Source: NCBI Gene, accessed 2026-10-07.
Protein reference (UniProt)
- Protein
Androgen receptor
- Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Subcellular location
Nucleus; Cytoplasm.
- Tissue specificity
Isoform 2: Mainly expressed in heart and skeletal muscle. Isoform 3: Expressed in basal and stromal cells of the prostate (at protein level).
- Associated conditions
Androgen insensitivity syndrome (AIS); Spinal and bulbar muscular atrophy X-linked 1 (SMAX1); Prostate cancer, hereditary, X-linked 3 (HPCX3); Androgen insensitivity, partial (PAIS); Hypospadias 1, X-linked (HYSP1).
Source: UniProtKB/Swiss-Prot P10275, release 2026_03, licensed CC BY 4.0. This is the protein’s normal biology, not evidence about post-drug syndromes; associated conditions are inherited disorders of the gene, not PFS, PSSD or PRSD.
Why its pathway is in the library
Nuclear receptors transduce steroid signals into lasting gene-expression programs; persistent receptor-level remodeling (or silencing) is a leading hypothesis for symptoms that outlast drug exposure.
Written for the whole nuclear receptors family, not for AR specifically.
Powers’ note (his unpublished theorizing)
Named by Powers (2026 summit interview + DWP-003, unpublished): citing published work (Khera) reporting ~1.7x androgen-receptor upregulation in PFS cells, he theorizes weak-metabolite crowding blocks potent androgens from binding and that extreme cases epigenetically silence AR expression — near-zero androgenic signaling despite normal blood levels.
Narrative library record
Function
Steroid-hormone-activated transcription factor (nuclear receptor subfamily 3, group C, member 4). On binding testosterone or DHT it sheds accessory proteins, moves to the nucleus, dimerizes, and switches on androgen-responsive genes. Its N-terminal domain carries two polymorphic trinucleotide repeats encoding polyglutamine (CAG) and polyglycine (GGN) tracts that modulate receptor activity.
Corpus relevance
Central to the corpus on two independent lines. Peer-reviewed: Cauci et al. 2017 (PFS-007) associated AR CAG/GGN repeat-length variants with different PFS symptom patterns in 66 patients, and the Baylor gene-expression report (PFS-008, preliminary) found AR overexpression in PFS penile skin. Powers: DWP-002 reframes the androgenic-signal-loss PFS subtype as intracellular weak-metabolite crowding at the AR (intracrine signaling), invisible to serum tests. Attribution: clinical-human (preliminary) plus theoretical-per-Powers.
- PFS-007Androgen Receptor (AR) Gene (CAG)n and (GGN)n Length Polymorphisms and Symptoms in Young Males With Long-Lasting Adverse Effects After Finasteride Use Against Androgenic Alopecia
- PFS-008Differential Gene Expression in Post-Finasteride Syndrome Patients (Baylor College of Medicine)
- DWP-002Untitled long-form research update — new model of PFS/PSSD/post-drug syndromes (Sept 2026)
- YT-iWFDBRTgT3gDr. Will Powers Interview [PFS / PAS / PSSD Summit 2026]
Powers’ claims naming AR
- Powers gene claim
ARID1A; CHD8; HDAC10 — recurring "glitches" (unspecified)
Confidence: interview
In whole-genome sequencing of ~100 PFS patients, glitches in epigenetic monitoring genes — ARID1A, CHD8, HDAC10 — appear "more than they should" statistically. Epigenetic flags (e.g., for AR upregulation) may fail to be removed after drug discontinuation.
ARARID1ACHD8HDAC10PGL-ARID1A-CHD8-HDAC102026-04-29PFS - Powers gene claim
AR — upregulated expression (~1.7x, citing Khera); theorized epigenetic silencing in his phenotype
Confidence: interview/direct
Citing Khera's published finding of ~1.7x AR upregulation in PFS cells, Powers theorizes intracellular weak-metabolite crowding blocks potent androgens from binding, and that in extreme cases the body epigenetically silences AR expression — producing…
ARPGL-AR2026-04-29; circa May 2026PFS
Mentioned in 38 corpus records
- Community accountAbout Powers’ workSelf-report · N=1
PFS/PSSD: I'm going to try something interesting…
u/various (r/DrWillPowers members) · r/DrWillPowers
A patient with ~3 years of PSSD followed by PFS described Powers' theory back to the community (metabolite backlog → epigenetic androgen-receptor changes → persistent "crash") and proposed a 30-day fast as an experiment: fasting blunts the HPG axis, induces…
ARDWP-0072026PFSPSSDCore corpus - 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 - Powers · Reddit commentCurated Powers pick
Re: The Problems with the Theory of Impaired Androgen Signaling caused by Metabolite Accumulation: A Peaceful Challenge to Dr. Powers’ Thesis
u/drwillpowers · r/DrWillPowers
Long reply to a community member's critique of his impaired-androgen-signaling theory. Powers concedes his earlier strong claim — that androgens must exit through DHT when UGTs are impaired — was overstated: testosterone can route through oxidation…
AKR1C3ARUGT2B17PRH-01172026-09-20T19:15:54ZPFSPowers Reddit history - Powers · Reddit commentCurated Powers pick
Protocol direction: full HPA shutdown (LH/FSH zero) → normalize the absurd metabolite marker → natural reboot…
u/drwillpowers · r/DrWillPowers
Replying to a commenter proposing HPTA shutdown followed by bypass hormones (Primobolan/E2/progesterone) to route around the UGT2B17 clearance defect, Powers describes his current protocol direction: shut the HPA axis fully off (LH/FSH to zero), then track…
ARUGT2B17PRH-15202026-04-14T22:12:28ZPowers Reddit history - Peer-reviewed paper
The post-finasteride syndrome: possible etiological mechanisms and symptoms
Herman H. J. Leliefeld, Frans M.J. Debruyne, Yacov Reisman · International Journal of Impotence Research
The authors review how 5-alpha-reductase inhibitors, though targeted at prostate and scalp, act on three reductase isoenzymes distributed across many organs including the brain. They argue the lipophilic drugs cross the blood-brain barrier and can suppress a…
ARLIT-0082023PFSLiterature sweep · Oct 2026 - Peer-reviewed paper
Epigenetic regulation of 5α reductase-1 underlies adaptive plasticity of reproductive function and pubertal timing
Ben Bar-Sadeh; Or E. Amichai; Lilach Pnueli; Khurshida Begum; Gregory Leeman; Richard D. Emes; Reinhard Stöger; Gillian R. Bentley · BMC Biology
Women who experienced high energetic demands in childhood show altered adult ovarian function and shorter reproductive lifespan, suggesting early-life programming of reproduction. Combining a mouse model with methylation analysis of proxy-tissue DNA from a…
ARSRD5A1LIT-0582022Literature sweep · Oct 2026 - Conference abstract
Differential Gene Expression in Post-Finasteride Syndrome Patients (Baylor College of Medicine)
Howell, S.; et al.; (Khera, Mohit — senior investigator) · Conference presentation; summarized by PFS Network
RNA microarray of penile skin from 26 PFS patients vs 26 controls found 1,446 genes over-expressed and 2,318 under-expressed; androgen receptor expression was significantly higher in patients, with differentially expressed AR coregulators including…
ARPFS-0082021PFSCore corpus - Peer-reviewed paper
The connection of 5-alpha reductase inhibitors to the development of depression
Thiraphat Saengmearnuparp; Bannakij Lojanapiwat; Nipon Chattipakorn; Siriporn Chattipakorn · Biomedicine & Pharmacotherapy
Clinical studies indicate that former users of 5-alpha-reductase inhibitors carry a higher incidence of depressive symptoms and neuropsychiatric side effects than non-users, yet the mechanisms behind depression in former users — sometimes called…
ARLIT-0512021PFSLiterature sweep · Oct 2026 - Peer-reviewed paperSIDEfxHUB pick
Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm
Abdulmaged M. Traish · The World Journal of Men's Health
Traish argues that dihydrotestosterone (DHT) is far more than a prostate-and-hair hormone, documenting its physiological roles in liver, pancreatic beta-cell function and survival, ocular and lacrimal function, and kidney physiology. Blocking DHT synthesis…
ARLIT-0502020PFSLiterature sweep · Oct 2026 - Peer-reviewed paper
Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective
Steven M. Paul; Graziano Pinna; Alessandro Guidotti · Neurobiology of Stress
Tracing three decades of research, the authors describe how allopregnanolone — synthesized in the CNS from cholesterol or from progesterone and pregnenolone — came to be recognized as a rapid, non-genomic modulator of GABA-A receptors. Shifts in brain…
ARLIT-0562020PFSLiterature sweep · Oct 2026 - Timeline event
Argues finasteride reprograms gene regulation (DNA methylation, histone modification, AR upregulation) — the theoretical origin of the epigenetic model.
ARTL-2018-traish-introduces-drug-induced-epigenetics-model-of-pfs-cur2018PFSCore corpus - Peer-reviewed paperSIDEfxHUB pick
Androgen Receptor (AR) Gene (CAG)n and (GGN)n Length Polymorphisms and Symptoms in Young Males With Long-Lasting Adverse Effects After Finasteride Use Against Androgenic Alopecia
Cauci, Sabina; Chiriacò, Giovanni; Cecchin, Erika; Toffoli, Giuseppe; Xodo, Serena; Stinco, Giuseppe; Trombetta, Carlo · Sexual Medicine · 5(1):e61-e71
In 66 PFS patients, short/long (CAG)n and (GGN)n repeat lengths in the androgen receptor gene were associated with different symptom frequencies (libido loss, genital sensitivity changes, muscle tone, skin dryness, etc.), with a U-shaped pattern for some…
ARPFS-0072017PFSCore corpus - Timeline event
Core genetic-susceptibility paper: AR (CAG)n/(GGN)n variants associated with different PFS symptom profiles — a precision-medicine angle for the corpus.
ARTL-2017-cauci-et-al-link-androgen-receptor-repeat-polymorphisms-to2017PFSCore corpus - Peer-reviewed paper
Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study
Giacomo Tirabassi, Giovanni Corona, Sara Falzetti, Nicola delli Muti, Mario Maggi, Giancarlo Balercia · International Journal of Endocrinology
No prior study had assessed the AR GGC repeat in sexual function. In 85 male outpatients evaluated with the IIEF-15, longer CAG repeats correlated inversely with erectile function, orgasmic function, and total IIEF score, while GGC tracts showed no…
ARMECH-0422016Systems review · Oct 2026 - 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 paper
Influence of Androgen Receptor CAG Polymorphism on Sexual Function Recovery after Testosterone Therapy in Late-Onset Hypogonadism
Giacomo Tirabassi; Giovanni Corona; Andrea Biagioli; Eddi Buldreghini; Nicola delli Muti; Mario Maggi; Giancarlo Balercia · The Journal of Sexual Medicine
Seventy-three men with late-onset hypogonadism were evaluated with the IIEF questionnaire and hormone panels before testosterone replacement therapy and again before their sixth testosterone injection. All sexual function domains improved with therapy, but…
ARLIT-0602015PFSLiterature sweep · Oct 2026 - Peer-reviewed paper
Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action
Giacomo Tirabassi; Angelo Cignarelli; Sebastio Perrini; Nicola delli Muti; Giorgio Furlani; Mariagrazia Gallo; Francesco Pallotti… · International Journal of Endocrinology
A decade of evidence shows that the androgen receptor CAG repeat polymorphism conditions the peripheral effects of testosterone across many tissues. Longer repeat tracts blunt receptor transactivation and thereby influence male sexual function and fertility…
ARLIT-0612015Literature sweep · Oct 2026 - 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 - Peer-reviewed paper
Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors
M. Schumacher; C. Mattern; A. Ghoumari; J.P. Oudinet; P. Liere; F. Labombarda; R. Sitruk-Ware; A.F. De Nicola · Progress in Neurobiology
This major review reconsiders progesterone and its 5-alpha-reduced metabolite allopregnanolone as central nervous system signaling molecules rather than mere reproductive hormones. It covers their synthesis in the brain, their potentiation of GABA-A receptor…
ARLIT-0532014Literature sweep · Oct 2026 - Peer-reviewed paper
Allopregnanolone: State of the art
Roberto Cosimo Melcangi; Gian Carlo Panzica · Progress in Neurobiology
Melcangi and Panzica consolidate the state of knowledge on allopregnanolone: its enzymatic synthesis via 5-alpha-reductase and 3alpha-hydroxysteroid dehydrogenase, its distribution in brain and periphery, and its potent modulation of GABA-A receptors. The…
ARLIT-0542014PFSLiterature sweep · Oct 2026 - Peer-reviewed paperSIDEfxHUB pick
A Pharmacogenetic Survey of Androgen Receptor (CAG)N and (GGN)N Polymorphisms in Patients Experiencing Long Term Side Effects after Finasteride Discontinuation
Erika Cecchin; Elena De Mattia; Giorgio Mazzon; Sabina Cauci; Carlo Trombetta; Giuseppe Toffoli · The International Journal of Biological Markers
The team compared the prevalence of two androgen receptor polymorphisms, CAG-rs4045402 and GGN-rs3138869, across 69 men with androgenetic alopecia who developed persistent side effects after finasteride, 91 untreated men with alopecia, and 76 untreated men…
ARSIDE-0112014PFSSIDEfxHUB picks - Peer-reviewed paperPSSD Discord pick
Prolonged treatment with bicalutamide induces androgen receptor overexpression and androgen hypersensitivity
Kawata H, Ishikura N, Watanabe M, Nishimoto A, Tsunenari T, Aoki Y · Prostate
Preclinical prostate-cancer study in which prolonged bicalutamide exposure produced a resistant cell subline that overexpressed androgen receptor protein and phosphorylated AR, proliferating at tenfold lower androgen concentrations than parent cells — without…
ARDISC-0042010PFSPSSD Discord picks - Peer-reviewed paper
Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone
J. M. Torres; E. Ortega · Journal of Molecular Endocrinology
5-alpha-reductase exists as two isoforms, type 1 associated with catabolic functions and type 2 with sexually dimorphic functions, and the authors had previously shown both are present and oppositely regulated by androgens in the adult male rat brain. This…
ARSRD5A1SRD5A2LIT-0572006PFSLiterature sweep · Oct 2026 - Peer-reviewed paper
17β-Hydroxy-5alpha-androst-1-en-3-one (1-testosterone) is a potent androgen with anabolic properties
Angelika Friedel; Hans Geyer; Matthias Kamber; Ute Laudenbach-Leschowsky; Wilhelm Schänzer; Mario Thevis; Günter Vollmer; Oliver Zierau… · Toxicology Letters
The only controlled pharmacology study of dihydroboldenone (1-testosterone, DHB): in castrated rats, equimolar 1-testosterone matched testosterone propionate in stimulating levator ani, ventral prostate, and seminal vesicle growth, with an anabolic/androgenic…
ARMECH-0112006Systems review · Oct 2026 - Peer-reviewed paper
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… · Nature
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…
ARKDM1AMECH-0442005Systems review · Oct 2026 - Dataset / resource
PFS Network
PFS Network (charity launched on Rare Disease Day 2021 by propeciahelp.com organizers)
patient advocacy org; research funder; science-summaries hub — public website; research updates via mailing list
ARDS-001PFSCore corpus - Dataset / resource
Published genetic/molecular datasets — AR polymorphisms, SRD5A2 methylation, gene expression
published study data (not public biobanks)
published study data (not public biobanks) — via papers; raw data availability varies — contact authors
ARSRD5A2DS-010PFSPSSDCore corpus - Glossary term
Androgen receptor (AR)
receptor
The nuclear receptor through which testosterone and DHT drive gene expression. The corpus reports it as OVEREXPRESSED in PFS penile skin (SIDE-009) and links AR gene CAG/GGN repeat variants to symptom patterns (PFS-007) — a compensatory upregulation that may…
ARGL-androgen-receptorPFSCore corpus - Glossary term
AR overexpression
epigenetic
Abnormally high androgen-receptor levels found in PFS penile-skin tissue versus controls (1,446 genes over-expressed overall). Interpreted as a compensatory — and possibly epigenetically locked — response to impaired androgen signaling.
ARGL-ar-overexpressionPFSCore corpus - Mechanism
AR gene polymorphisms (CAG/GGN repeat lengths)
PFS: supported · PSSD: suggested · PRSD: unstudied
The strongest human genetic-susceptibility finding in the corpus, from two studies by one Trieste group whose PFS cohorts (69 and 66) may overlap (SIDE-011, PFS-007); a US study of 25 men found no explanatory AR or SRD5A variants (SIDE-010). PFS-only; needs…
ARMECH-04PFSCore corpus - Open question
Is there human in-vivo proof of lasting epigenetic changes, or is the epigenetic model still hypothesis?
Hypothesis with suggestive but incomplete human evidence
Epigenetic reprogramming is the mechanism vs Hypothesis awaiting human proof. Hypothesis with suggestive but incomplete human evidence
AROQ-003Core corpus - Gene recordPowers’ theory
AKR1C2 — aldo-keto reductase family 1 member C2
10p15-p14 (AKR1C gene cluster, chromosome 10)
3-alpha-hydroxysteroid dehydrogenase type 3; interconverts DHT and the much weaker 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol), effectively switching DHT's androgenic signal off, and participates in synthesis of neurosteroids such as…
AKR1C1AKR1C2AKR1C3AKR1C4AR+1GENE-AKR1C2PFSCore corpus - Gene record
3-oxo-5-alpha-steroid 4-dehydrogenase 2; the dominant isoenzyme in prostate and genital skin, converting testosterone to DHT. Loss-of-function variants cause 5-alpha-reductase-2 deficiency, a 46,XY difference of sex development - direct human proof of what…
AKR1C2ARSRD5A1SRD5A2SRD5A3GENE-SRD5A2PFSCore corpus - Gene recordPowers’ theory
Core DNA-binding subunit of the mammalian SWI/SNF (BAF) chromatin-remodeling complex; uses an ARID domain to bind AT-rich DNA and targets the remodeling complex to chromatin, regulating transcription, DNA repair, and differentiation. Frequently mutated in…
ARARID1ACHD8HDAC10GENE-ARID1APFSCore corpus - Gene recordPowers’ theory
HDAC10 — histone deacetylase 10
22q13.33
Class IIb histone deacetylase that removes acetyl groups from lysine residues on core histones (and polyamines such as N8-acetylspermidine), producing a tag for epigenetic repression; acts in large multiprotein complexes to regulate transcription, cell-cycle…
ARARID1ACHD8HDAC10GENE-HDAC10PFSCore corpus - Gene recordPowers’ theory
UGT2B15 — UDP glucuronosyltransferase family 2 member B15
chromosome 4 (UGT2B gene cluster, 4q13 region)
Androgen-conjugating UGT expressed in liver, prostate, adipose, skin, and other tissues; glucuronidates DHT, androsterone, and androstane-3-alpha,17-beta-diol, directly terminating their activity and marking them for urinary excretion.
AKR1C2ARUGT1A1UGT2B15UGT2B17+1GENE-UGT2B15Core corpus - Gene record
Dual-function P450 enzyme with 17-alpha-hydroxylase and 17,20-lyase activities - the key branch point of steroidogenesis that diverts pregnenolone/progesterone toward glucocorticoids versus DHEA and androstenedione (androgen precursors). Expressed in…
ARCYP17A1CYP19A1HSD3B2SRD5A1GENE-CYP17A1PFSPSSDCore corpus - Gene record
Aromatase - the P450 enzyme catalyzing the final steps of estrogen biosynthesis, converting androgens (testosterone, androstenedione) to estrogens (estradiol, estrone). Tissue-specific promoters drive expression in placenta, gonads, adipose, and brain…
AKR1C3ARCYP17A1CYP19A1HSD3B2GENE-CYP19A1PFSPSSDCore corpus
Also in steroid and nuclear hormone receptors
All 41 genes- ESR1
estrogen receptor 1
chr 6· Nuclear receptors· 1 record - ESR2
estrogen receptor 2
chr 14· Nuclear receptors· Pathway candidate - FOXA1
forkhead box A1
chr 14· Nuclear receptors· Pathway candidate - HNF4A
hepatocyte nuclear factor 4 alpha
chr 20· Nuclear receptors· Pathway candidate - HNF4G
hepatocyte nuclear factor 4 gamma
chr 8· Nuclear receptors· Pathway candidate - NCOA1
nuclear receptor coactivator 1
chr 2· Nuclear receptors· Pathway candidate - NCOA2
nuclear receptor coactivator 2
chr 8· Nuclear receptors· Pathway candidate - NCOA3
nuclear receptor coactivator 3
chr 20· Nuclear receptors· Pathway candidate
Browse by family on the gene families page.