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

Although the mechanisms are not understood, evidence suggests that 17 beta-estradiol (E-2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E-2 decreases angiotensin type 1 receptors (AT(1)Rs) in different tissues and hypothesize that E-2 exerts tonic inhibition on AT(1)Rs, reducing effects of ANG II. This study determined the effects of E-2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT(1)R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx +/- E-2; Cas +/- DHT) for 3 wk. Cortical ER alpha protein was 2.5 times greater, and ER beta was 80% less in females vs. males (P < 0.01). Glomerular AT(1)R binding was lower in females than males [4,657 +/- 838 vs. 7,457 +/- 467 counts per minute (cpm), P < 0.01]. Ovx reduced ER alpha protein by 50%, whereas E-2 increased ER alpha expression after Ovx. The decrease in cortical ER alpha in Ovx rats was associated with a significant increase in AT(1)R binding (6,908 +/- 609 cpm), and E-2 prevented this increase. There was no change in ER alpha or AT(1)R binding following Cas +/- DHT (25 mg) treatment, although Cas did elevate cortical ER beta (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ER alpha 150% above intact levels and profoundly decreased AT(1)R binding (1,824 +/- 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT(1)R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E-2 regulates ER alpha and is inversely associated with glomerular AT(1)R binding, supporting our hypothesis that E-2 tonically suppresses AT(1)Rs and suggesting a potential mechanism for the protective effects of estrogen.