Chronic estradiol treatment decreases angiotensin II receptor density in the anterior pituitary gland and adrenal cortex but not in the mesenteric artery.
Chronic estrogen treatment has been shown to produce a marked reduction in anterior pituitary angiotensin II (AII) receptor density. In order to determine whether this effect is generalized, we studied the effect of chronic estradiol treatment on AII receptor density in the anterior pituitary gland, adrenal cortex and mesenteric artery of ovariectomized (OVX) rats. Treated rats were injected daily with 25 micrograms of estradiol valerate while controls received only the vehicle. Binding affinity and density of AII receptors were measured using the AII antagonist [125I]-Sar1Ile8 AII ([125I]-SARILE). Following 7-, 14- or 28-day treatments, AII receptor density decreased by approximately 80% in the anterior pituitary; 30% in the adrenal cortex and remained the same in mesenteric artery particulate fractions. In all 3 target tissues, dissociation constants (KD) for binding of [125I]-SARILE were in the nanomolar range and were the same between control and treated rats. Using conscious rats, estradiol treatment for 7 days was also shown to block the release of aldosterone by low dose infusions of AII (10 ng/min, 30 min). Plasma AII and plasma renin activity were also the same or slightly decreased following estradiol treatments. This study suggests that estrogens may be important modulators of the AII receptor and may be directly involved in modulating target cell responsiveness to AII as expressed through differential down-regulation of AII receptors.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D004958:Estradiol; C032651:angiotensin II, Sar(1)-Ile(5)-; D012083:Renin