HSD17B2
hydroxysteroid 17-beta dehydrogenase 2
Theoretical — per Powers
Gene summary
A protein-coding gene on chromosome 16 (steroid hormone synthesis). Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in androgen metabolic process; estrogen biosynthetic process; and response to retinoic acid.
Source: NCBI Gene, accessed 2026-10-07.
Protein reference (UniProt)
- Protein
17-beta-hydroxysteroid dehydrogenase type 2
- Function
Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity.
- Subcellular location
Endoplasmic reticulum membrane.
- Tissue specificity
Expressed in placenta.
Source: UniProtKB/Swiss-Prot P37059, 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 HSD17B2 specifically.
Powers’ note (his unpublished theorizing)
Named by Powers (DWP-003, unpublished): a defective HSD17B2 impairs testosterone-to-androstenedione conversion, worsening androgen backup (androstenedione still needs glucuronidation, sulfation, or aromatization for exit).
Narrative library record
Function
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 inactivation, and also shows 20-alpha-HSD activity.
Corpus relevance
Powers named HSD17B2 in his DWP-003 post: a defective enzyme impairs testosterone-to-androstenedione conversion, worsening the androgen backup. Because androstenedione remains androgenic and still requires glucuronidation, sulfation, or aromatization for exit, losing this escape route compounds the UGT2B17 core defect after finasteride closes the DHT exit. The enzyme's normal role is antiandrogenic (it inactivates testosterone), so its defect removes an inactivation pathway. Attribution: theoretical-per-Powers (unpublished Reddit theorizing); no PFS patient variant data in corpus.
Powers’ claims naming HSD17B2
- Powers gene claim
HSD17B2 — defective
Confidence: direct
A defective HSD17B2 (which converts testosterone to androstenedione) worsens the backup; androstenedione remains androgenic and still requires glucuronidation, sulfation, or aromatization for exit.
HSD17B2PGL-HSD17B2circa May 2026PFS
Mentioned in 2 corpus 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 - Gene recordPowers’ theory
Cytosolic sulfotransferase expressed in liver and adrenal glands that catalyzes the sulfation of steroids and bile acids, converting them into water-soluble sulfate conjugates for excretion; variants are studied for effects on circulating DHEA-sulfate levels.
HSD17B2SLCO1B1SULT2A1UGT2B15UGT2B17+1GENE-SULT2A1PFSCore corpus
Also in steroid hormone synthesis
All 38 genes- SRD5A2
steroid 5 alpha-reductase 2
chr 2· Steroid synthesis· 19 records - 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
Browse by family on the gene families page.