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Am J Physiol Regul Integr Comp Physiol (September 21, 2006). doi:10.1152/ajpregu.00424.2006
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Submitted on June 16, 2006
Accepted on September 19, 2006

EFFECT OF SEX HORMONES ON RENAL ESTROGEN AND ANGIOTENSIN TYPE 1 RECEPTORS (AT1R) IN FEMALE AND MALE RATS

Jennifer L Rogers1, Adam R Mitchell1, Christine Maric2, Kathryn Sandberg3, Adam Myers4, and Susan E. Mulroney5*

1 Physiology & Biophysics, Georgetown University Medical Center, Washington, District of Columbia, United States
2 Medicine and Physiology, Georgetown University Medical Center, Washington, District of Columbia, United States
3 Dept Med and Physiol, Georgetown U Med Ctr, 232 Bldg D,4000 Reservoir Rd, NW, Washington, DC, 20007-2145, United States; Dept Med and Physiol, Georgetown University Medical Center, Washington, DC, District of Columbia, United States
4 Department of Physiology and Biophysics, Georgetown University Medical Center, Washington,, District of Columbia, United States
5 Department of Physiology, Georgetown University Medical Center, Washington, District of Columbia, United States

* To whom correspondence should be addressed. E-mail: mulrones{at}georgetown.edu.

While the mechanisms are not understood, evidence suggests that 17{beta}-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We reported that E2 decreases AT1Rs in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of angiotensin II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ER) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy/Ovx or orchidectomy/Cas and were treated (Ovx+/-E2; Cas+/-DHT) for 3 weeks. Cortical ER{alpha} protein was 2.5X greater, and ER{beta} was 80% less in females vs males (P<0.01). Glomerular AT1R binding was lower in females vs males (4657±838 vs 7457±467 cpm, P<0.01). Ovx reduced ER{alpha} by 50%, while E2 increased ER{alpha} protein after Ovx. The decrease in cortical ER{alpha} in Ovx rats was associated with a significant increase in AT1R binding (6908±609 cpm); E2 prevented this increase. There was no change in ER{alpha} or AT1R binding following Cas+/-DHT (25 mg) treatment, although Cas elevated cortical ER{beta} (P<0.01). Interestingly, the high dose DHT (200 mg) elevated ER{alpha} 150% above intact levels, and profoundly decreased AT1R binding (1824±705 cpm, P<0.001 vs intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male vs female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ER{alpha} 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.




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