title: 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 17beta-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 ERalpha protein was 2.5 times greater, and ERbeta 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 ERalpha protein by 50%, whereas E2 increased ERalpha expression after Ovx. The decrease in cortical ERalpha 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 ERalpha or AT1R binding following Cas +/- DHT (25 mg) treatment, although Cas did elevate cortical ERbeta (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERalpha 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 ERalpha 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.
authors.affiliation: Department of Physiology and Biophysics, Georgetown University, Medical Center, Washington, DC 20057, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Rogers
authors.forename: Adam R
authors.initials: AR
authors.lastname: Mitchell
authors.forename: Christine
authors.initials: C
authors.lastname: Maric
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sandberg
authors.forename: Adam
authors.initials: A
authors.lastname: Myers
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mulroney
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000502:physiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D012727:Sex Characteristics
chemical_list: D012739:Gonadal Steroid Hormones; D044140:Receptor, Angiotensin, Type 1; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D004958:Estradiol