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

Abstract

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.

Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics

“…The kinetic constant was based on the non-linear analysis and the Michaelis–Menten method gave a whole-cell K m value of 9.287 µM. Previous studies have shown a testosterone affinity, with K m value ranging from 1 to 5 µM in other cell lines, including dermal papilla, prostate cancer, and sebaceous glands 39 , 41 , 42 . Non-linear modeling of experimentally evaluated V max in the absence of inhibitors gave a V max value of 130.9.…”