CALL FOR PAPERS Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats

Rogers, JL, Mitchell AR, Maric C, Sandberg K, Myers A, Mulroney SE. Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats. Am J Physiol Regul Integr Comp Physiol 292: R794 –R799, 2007. First published September 21, 2006; doi:10.1152/ajpregu.00424.2006.— Although the mechanisms are not understood, evidence suggests that 17 -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 ER protein was 2.5 times greater, and ER 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 ER protein by 50%, whereas E2 increased ER expression after Ovx. The decrease in cortical ER 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 ER or AT1R binding following Cas DHT (25 mg) treatment, although Cas did elevate cortical ER (P 0.01). Interestingly, the high dose DHT (200 mg) elevated ER 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 ER 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.