Sex Steroids and Renal Disease

Abstract

Epidemiological studies have shown that male sex is an independent risk factor for the development and progression of renal disease, and men progress to end stage renal disease (ESRD) faster than premenopausal women in such diseases as autoimmune glomerulonephritis, hypertensive glomerulosclerosis, and polycystic kidney disease.1–3 Although the age-related decline in renal function is also faster in men, women become more susceptible to renal diseases after menopause.4 Insight from in vitro studies and animal models suggest that sex steroids play pivotal roles in modifying the progression to ESRD. Because there is a paucity of data in humans showing the mechanisms by which sex steroids impact renal disease, most of the studies discussed this review will be in animals, mainly rats. Furthermore, determining the roles of sex steroids in various diseases has been done using gonedectomized animals; however, although gonadectomy removes more than sex steroids and most studies only replace the sex steroid of interest, these are still the best studies in which to evaluate mechanisms responsible for sex differences in renal disease. Studies in postmenopausal women will also be kept to a minimum in this review because it is likely that sex steroids change action with aging, as suggested by the Women’s Health Initiative study. Estrogen receptors (ER) are present in the kidney, although their localization in nephron segments has not been fully elucidated. Mesangial cells contain both ERα and ERβ,5 as do endothelium and vascular smooth muscle cells.5–7 Whether the newly described transmembrane estrogen receptor, GPR30,8 is present in kidneys has not been determined. Ovariectomy (ovx) of Dahl salt sensitive rats (DS) caused decreases in ERα but increases in ERβ expression in the renal cortex and medulla,9 whereas ovx in salt resistant (DR) rats caused decreases in cortical and increases in medullary ERα, and …