Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats

Abstract

Although the mechanisms are not understood, evidence suggests that 17β-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E2 decreases angiotensin type 1 receptors (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx ± E2; Cas ± DHT) for 3 wk. Cortical ERα protein was 2.5 times greater, and ERβ was 80% less in females vs. males ( P < 0.01). Glomerular AT1R binding was lower in females than males [4,657 ± 838 vs. 7,457 ± 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERα protein by 50%, whereas E2 increased ERα expression after Ovx. The decrease in cortical ERα in Ovx rats was associated with a significant increase in AT1R binding (6,908 ± 609 cpm), and E2 prevented this increase. There was no change in ERα or AT1R binding following Cas ± DHT (25 mg) treatment, although Cas did elevate cortical ERβ (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERα 150% above intact levels and profoundly decreased AT1R binding (1,824 ± 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ERα and is inversely associated with glomerular AT1R binding, supporting our hypothesis that E2 tonically suppresses AT1Rs and suggesting a potential mechanism for the protective effects of estrogen.