The Brain, the Penis and Steroid Hormones: Clinical Correlates with Endothelial Dysfunction

Abdulmaged   M.   Traish; Hilal      Abu-Zahra; Andre   T.   Guay

Abstract

Erectile function is a complex neurovascular process that depends on the health of the central and peripheral nervous systems and the vasculature. Thus, signaling from the central nervous system (brain) to the peripheral nervous system (penis) is critical and is modulated by a set of complex interactions that depend on cerebral and vascular circulation. The cerebral and peripheral vasculatures are target tissues for sex steroid hormones. Gonadal, adrenal and neurosteroids regulate the function and physiology of the endothelium and modulate vascular and cerebral circulation by genomic and non-genomic dependent mechanisms. Recent advances in cell and molecular biology have defined a critical role of endothelium in vascular function. A host of biochemical and clinical markers of endothelium function and dysfunction have been identified to assess vascular pathology. Emerging evidence suggests that sex steroid hormones play an important role in maintaining endothelial health and sex steroid deficiency is associated with endothelial dysfunction, vascular disease and erectile dysfunction. Such information has important clinical implications in patient management with sex steroid hormone insufficiency, diabetes, metabolic syndrome, vascular disease and erectile dysfunction. In this review, we discuss the role of sex steroid hormones in modulation of the biochemical and clinical markers associated with endothelial dysfunction. Specifically the regulation of endothelial nitric oxide synthase, assymetric dimethylarginine, reactive oxygen species, endothelin-1, inflammatory cytokines, tumor necrosis factor-α, markers of cell adhesion, dysregulation of fibrinolytic factors and the inability to regenerate from endothelial progenitor cells concomitant with increased endothelial apoptosis, increased cellular permeability and increased vascular tone.

Keywords: Sex steroids, neurosteroids, endothelium dysfunction, erectile dysfunction, nitric oxide, nitric oxide synthase, vascular tone, vascular disease