SRD5A2
steroid 5 alpha-reductase 2
Gene summary
A protein-coding gene on chromosome 2 (steroid hormone synthesis). Encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride.
Source: NCBI Gene, accessed 2026-10-07.
Protein reference (UniProt)
- Protein
3-oxo-5-alpha-steroid 4-dehydrogenase 2
- Function
Catalyzes the irreversible stereospecific reduction of the delta 4,5 bond (double bond between carbons 4 and 5) of various 3-oxo steroids (3-keto steroids) producing their 5alpha dihydro-3-oxo forms. Converts testosterone into 5-alpha-dihydrotestosterone (DHT), the most active androgen in the prostate, as it is the preferred ligand for androgen receptor (AR) transactivation, making this reaction a key step in male sexual differentiation during development. Besides testosterone, it can also act on other steroids, including progesterone, producing metabolites with diverse roles. Hence, it plays a central role in sexual differentiation and androgen physiology.
- Subcellular location
Microsome membrane; Endoplasmic reticulum membrane.
- Tissue specificity
Expressed in high levels in the prostate and many other androgen-sensitive tissues.
- Associated conditions
Pseudovaginal perineoscrotal hypospadias (PPSH).
Source: UniProtKB/Swiss-Prot P31213, 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
Steroid-synthesis enzymes sit directly on the pathways perturbed by 5-alpha-reductase inhibitors and SSRIs; inherited variation here is a candidate susceptibility factor for persistent post-drug phenotypes.
Written for the whole steroid synthesis family, not for SRD5A2 specifically.
Narrative library record
Function
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 impaired SRD5A2 does to androgen signaling.
Corpus relevance
The primary finasteride target and the most genetically studied gene in the corpus: a pilot study found differential SRD5A2 methylation in PFS cerebrospinal fluid versus controls (PFS-011; also DS-010 in the datasets guide), tying the drug's own target gene to epigenetic change - the core of Traish's drug-induced-epigenetics model (PFS-001, PFS-002). Powers' entire framework (DWP-001, DWP-002) starts from 5AR blockade. Attribution: peer-reviewed (pilot human data, preliminary).
- PFS-001Post-finasteride syndrome: a surmountable challenge for clinicians
- PFS-002The post-finasteride syndrome: clinical manifestation of drug-induced epigenetics due to endocrine disruption
- PFS-004Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology
- PFS-005Patients treated for male pattern hair with finasteride show, after discontinuation of the drug, altered levels of neuroactive steroids in cerebrospinal fluid and plasma
- PFS-0115α-Reductase Isoenzymes: From Neurosteroid Biosynthesis to Neuropsychiatric Outcomes
- DWP-001Has anyone here taken finasteride or dutasteride and gotten post finasteride syndrome (PFS) from them? I have a theory as to why this seems to happen in transgender women more than cis men
- DWP-002Untitled long-form research update — new model of PFS/PSSD/post-drug syndromes (Sept 2026)
- DS-010Published genetic/molecular datasets — AR polymorphisms, SRD5A2 methylation, gene expression
Mentioned in 18 corpus records
- Peer-reviewed paper
5α-Reductase Isoenzymes: From Neurosteroid Biosynthesis to Neuropsychiatric Outcomes
Rodríguez-Cerdeira, Carmen; Freus, Marika; Misiakiewicz-Has, Kamila; Pilutin, Anna; Kolasa, Agnieszka; Maksym, Radoslaw; Kajdy, Anna · NeuroSci (systematic review; PRISMA 2020)
PRISMA systematic review (PubMed/Scopus/Web of Science to Feb 2025; 83 included articles) on SRD5A1/2/3 tissue distribution: SRD5A1 drives CNS allopregnanolone synthesis; impaired neurosteroidogenesis from 5α-reductase inhibition is linked to anxiety…
SRD5A1SRD5A2SRD5A3PFS-0112025Core corpus - Peer-reviewed paper
Prefrontal 5α-reductase 2 mediates male-specific acute stress response
Roberto Cadeddu; Giulia Braccagni; Gabriele Floris; Caterina Branca; Eleonora Corridori; Sara Salviati; Pilar Sánchez; Luca Spiro… · Science Advances
Acute stress selectively raises 5α-reductase type 2 — not type 1 — in the medial prefrontal cortex of male rats, and 5αR2 knockdown or knockout blunts the hormonal and behavioral stress response in males only. The authors demonstrate a division of labor: 5αR1…
SRD5A1SRD5A2MECH-0082025Systems review · Oct 2026 - Peer-reviewed paper
Finasteride Induces Epigenetic Alteration of TMPRss2 Gene Expression: A Potential role in Severe Acute Respiratory Syndrome-Corona Virus-2 Inhibition
Churchill Jonadab Ihentuge, Antonei Benjamin Csoka · Journal of Pharmacology and Experimental Therapeutics
Reports that finasteride induces epigenetic alteration of TMPRSS2 gene expression. The paper's framing concerns SARS-CoV-2 (TMPRSS2 is an androgen-regulated host protease), but the mechanistic finding is the point for this corpus: a 5-alpha-reductase…
SRD5A2EPI-0012023PFSEpigenetics supplement · Oct 2026 - Peer-reviewed paper
Methylated CpG dinucleotides in the 5-alpha reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients
Zhemin Lin, Dongdong Fan, Song Jin, Zhanliang Liu, Yi-Nong Niu · Asian Journal of Andrology
Finds methylated CpG dinucleotides in the SRD5A2 gene and proposes that methylation status of the 5-alpha-reductase-2 gene explains variable finasteride response in benign prostatic enlargement patients. DNA methylation at the very locus encoding…
SRD5A1SRD5A2EPI-0022021PFSEpigenetics supplement · Oct 2026 - Peer-reviewed paper
Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride
Qingpin Xiao, Lei Wang, Shreyas Supekar, Tao Shen, Heng Liu, Fei Ye, Junzhou Huang, Hao Fan, Zhiyi Wei, Cheng Zhang · Nature Communications
The authors reported the first atomic structure of human steroid 5-alpha-reductase 2, the enzyme finasteride inhibits, resolved at 2.8 angstroms. It revealed an unusual seven-transmembrane topology. The bound ligand was not finasteride itself but an…
SRD5A2LIT-0112020PFSLiterature sweep · Oct 2026 - Peer-reviewed paperPSSD Discord pickSIDEfxHUB pick
Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study
Roberto Cosimo Melcangi, Livio Casarini, Marco Marino, Daniele Santi, Samantha Sperduti, Silvia Giatti, Silvia Diviccaro, Maria Grimoldi… · Endocrine Connections
In this pilot case-control study, 16 PFS patients were compared with 36 controls who had never used finasteride: 18 surgical patients giving cerebrospinal fluid (2 of whom also gave blood) and 18 blood-only donors; controls' mean age was 40.8 years vs 34.5 in…
SRD5A1SRD5A2DISC-0252019PFSPSSDPSSD Discord picks - Peer-reviewed paper
Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial
Cindy H. Chau, Douglas K. Price, Cathee Till, Phyllis J. Goodman, Xiaohong Chen, Robin J. Leach, Teresa L. Johnson-Pais, Ann Wu Hsing… · PLoS ONE
Using a nested case-control design inside the Prostate Cancer Prevention Trial, the authors measured serum finasteride by validated LC-MS and tested 27 SNPs in finasteride target and metabolism genes for association with drug concentrations. Five SNPs in…
CYP3A4CYP3A5SRD5A2SRD5A3MECH-0432015PFSSystems review · Oct 2026 - 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 - 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
SRD5A2
enzyme
Gene encoding 5-alpha-reductase type 2, dominant in prostate and genital skin. A pilot study found differential SRD5A2 methylation in PFS cerebrospinal fluid versus controls, linking the drug's target gene itself to epigenetic changes.
SRD5A2GL-srd5a2PFSCore corpus - Glossary term
DNA methylation
epigenetic
An epigenetic mark that silences genes without changing DNA sequence. Central to Traish's 'drug-induced epigenetics' model: finasteride is proposed to trigger lasting methylation changes (e.g., at SRD5A2) that persist after the drug is gone.
SRD5A2GL-dna-methylationPFSCore corpus - Gene recordPowers’ theory
AKR1C1 — aldo-keto reductase family 1 member C1
10p15-p14 (AKR1C gene cluster, chromosome 10)
Cytosolic NAD(P)H-dependent oxidoreductase with mainly 20-alpha-hydroxysteroid dehydrogenase activity; converts progesterone to the inactive 20-alpha-hydroxyprogesterone and also reduces a range of aldehydes, ketones, and xenobiotics. One of four closely…
AKR1C1AKR1C2AKR1C3AKR1C4SRD5A1+1GENE-AKR1C1PFSCore 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
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…
AKR1C2ARCYP17A1HSD3B2SRD5A2GENE-ARPFSCore corpus - Gene record
3-oxo-5-alpha-steroid 4-dehydrogenase 1; converts testosterone to the more potent DHT and reduces progesterone, corticosterone, and other steroids via 5-alpha-reduction (hydride transfer from NADPH to carbon 5). Also active in bile-acid biosynthesis; broadly…
AKR1C2HSD3B1SRD5A1SRD5A2SRD5A3GENE-SRD5A1PFSCore corpus - Gene record
Third 5-alpha-reductase isoenzyme (318 amino acids; about 20 percent homology with types 1 and 2); less characterized than types 1 and 2, with roles in protein N-glycosylation as well as steroid reduction.
SRD5A1SRD5A2SRD5A3GENE-SRD5A3PFSCore corpus - Gene record
The adrenal/gonadal isoform of 3-beta-HSD, predominantly expressed in adrenals, ovaries, and testes; catalyzes the same essential delta-5-to-delta-4 steroid conversion. Deficiency causes a rare congenital adrenal hyperplasia.
CYP17A1CYP19A1HSD3B1HSD3B2SRD5A2GENE-HSD3B2PFSPSSDCore corpus - Gene recordPowers’ theory
Short-chain dehydrogenase/reductase (17-beta-HSD type 2) that inactivates sex steroids, oxidizing testosterone to androstenedione, estradiol to estrone, and androstenediol to DHEA; described as the key 17-beta-HSD isozyme in androgen and estrogen…
AKR1C2CYP17A1CYP19A1HSD17B2SRD5A2+1GENE-HSD17B2PFSCore corpus
Also in steroid hormone synthesis
All 38 genes- SRD5A1Powers
steroid 5 alpha-reductase 1
chr 5· Steroid synthesis· 17 records - AKR1C2Powers
aldo-keto reductase family 1 member C2
chr 10· Steroid synthesis· 12 records - AKR1C3Powers
aldo-keto reductase family 1 member C3
chr 10· Steroid synthesis· 9 records - CYP17A1
cytochrome P450 family 17 subfamily A member 1
chr 10· Steroid synthesis· 9 records - AKR1C4Powers
aldo-keto reductase family 1 member C4
chr 10· Steroid synthesis· 8 records - AKR1C1Powers
aldo-keto reductase family 1 member C1
chr 10· Steroid synthesis· 7 records - HSD3B2
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2
chr 1· Steroid synthesis· 7 records - SRD5A3
steroid 5 alpha-reductase 3
chr 4· Steroid synthesis· 6 records
Browse by family on the gene families page.