5α-Reductases in Human Physiology: An Unfolding Story
Traish AM. Endocr Pract. 2012 Jul 11:1-38. [Epub ahead of print]

Source

Department of Urology, Boston University School of Medicine, Boston, Massachusetts, USA.

Abstract

Objective: 5α-reductases are a family of isozymes expressed in a wide host of tissues including the central nervous system and play a pivotal role in male sexual differentiation, development and physiology.Methods: A comprehensive literature search from 1970-2011 was made via PubMed and the relevant information was summarized.Results: 5α reductases convert testosterone, progesterone, deoxycorticosterone, aldosterone and corticosterone into their respective 5α -dihydro-derivatives, which serve as substrates for 3α - hydroxysteroid dehydrogenase (3α-HSD) enzymes. The latter transforms these 5α-reduced metabolites into a subclass of neuro-active steroid hormones with distinct physiological function. The neuro-active steroid hormones modulate multitude of functions in human physiology encompassing regulation of sexual differentiation, neuro-protection, memory enhancement, anxiety, sleep and stress, among others. In addition, 5α -reductase type 3 is also implicated in the N-glycosylation of proteins via formation of dolichol phosphate. The family of 5α-reductases was targeted for drug development to treat pathophysiological conditions, such as benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA). While the clinical use of 5α-reductases inhibitors was well established, the scope and the magnitude of the adverse side effects of such drugs especially on the central nervous systems is still unrecognized, due to lack of knowledge of the various physiological function of this family of enzymes, especially in the central nervous system.Conclusion: There is an urgent need to better understand the function of 5α-reductases and the role of neuro-active steroids in human physiology in order to minimize the potential adverse side effects of inhibitors targeting 5α-reductases to treat BPH and AGA.