3-oxo-5-alpha-steroid 4-dehydrogenase 3 (SRD5A3) (SRD5A3)

3-oxo-5-alpha-steroid 4-dehydrogenase 3 (SRD5A3) is a multifunctional enzyme that plays a critical role in both steroid metabolism and protein glycosylation (UniProt P0C6D5). It was originally identified for its ability to catalyze the conversion of testosterone into dihydrotestosterone (DHT), a potent androgen that drives the growth of prostate tissue (PubMed: 18923062). Beyond its androgenic role, SRD5A3 functions as a polyprenol reductase, converting polyprenol to dolichol, which is an essential lipid carrier for N-linked glycosylation of proteins (PubMed: 20637608). In clinical medicine, mutations in SRD5A3 are associated with congenital disorders of glycosylation (CDG-Iq) and Kahrizi syndrome, characterized by intellectual disability and ocular malformations (NCBI Gene: 79644). In the context of oncology, SRD5A3 is frequently overexpressed in castration-resistant prostate cancer (CRPC), where it contributes to intra-tumoral androgen synthesis, allowing the cancer to bypass traditional androgen deprivation therapies (PubMed: 21454540). While traditional 5-alpha-reductase inhibitors like finasteride primarily target types 1 and 2, SRD5A3 has emerged as a potential therapeutic target for overcoming drug resistance in advanced prostate cancer (PubMed: 22535194).

Other names

Steroid 5-alpha-reductase 3Polyprenol reductaseSRD5A2LSRD5A2L1

Inhibition of the enzymatic reduction of testosterone to dihydrotestosterone and the conversion of polyprenol to dolichol.