Steroidal 5α-Reductase: A Therapeutic Target for Prostate Disorders

Steroidal 5α-reductase is a system of NADPH dependent enzyme that catalyzes the irreversible conversion of Δ4–3-ketosteroid precursor (testosterone) to its corresponding 5α-reduced metabolite (dihydrotestosterone). Initial role of DHT was discovered through males pseudohermaphroditism, a genetic disorder with complete or partial 5α-reductase deficiency accompanied with features at critical juncture of fetal and postnatal development. However, excessive DHT production, has brought a revolution in revealing the etiology of complications like prostate cancer and benign prostatic hyperplasia. Over the last two decades, converging lines of evidences have highlighted the role of 5α-reductase inhibitors in the treatment of these androgen dependent disorders. Finasteride and Dutasteride, are the two clinically approved inhibitors available in the market, that helps in reducing the prostate volume by blocking the 5a-reductase enzyme.

Novel mutations of the SRD5A2 and AR genes in Thai patients with 46, XY disorders of sex development

Background:Abnormalities of dihydrotestosterone conversion [5α-reductase deficiency: online Mendelian inheritance in man (OMIM) 607306] or actions of androgens [partial androgen insensitivity syndrome (PAIS): OMIM 312300] during the 8th–12th weeks of gestation cause varying degrees of undervirilized external genitalia in 46, XY disorders of sex development (DSD) with increased testosterone production. The objective of the study was to determine clinical and genetic characteristics of Thai patients with 46, XY DSD.Methods:A cross-sectional study was conducted in 46, XY DSD with increased testosterone production (n=43) evaluated by a human chorionic gonadotropin (hCG) stimulation test or clinical features consistent with 5α-reductase deficiency or PAIS. PCR sequencing of the entire coding regions of theResults:Mutations were found in seven patients (16.3%): five (11.6%) and two (4.7%) patients had mutations inConclusions:Around 16.3% of our patients with 46, XY DSD had 5α-reductase deficiency or PAIS. Two novel mutations of