title: Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5' leader sequence of the receptor mRNA.
abstract: Two of the most highly recognized factors implicated in the pathogenesis of hypertension, atherosclerosis, congestive heart failure and associated cardiovascular disease are the renin angiotensin system (RAS) and estrogen. A major effect of estrogen results from its influence on the RAS. Beta-estradiol (E2) replacement in ovariectomized (OVX) rats significantly decreased type 1 angiotensin (AT1) receptor expression in the pituitary and adrenal, whereas it significantly increased receptor expression in the uterus when compared to OVX controls. Additional evidence demonstrated an important influence of estrogen on a recently discovered post-transcriptional mechanism for regulating expression of the AT1 receptor. This mechanism consists of cytosolic RNA binding proteins (BPs) that recognize the 5' leader sequence (5'LS) of the receptor mRNA. The activities of these 5'LS BPs were modulated by estrogen in an inverse manner to AT1 receptor regulation. Moreover, in vitro translation assays in wheat germ lysates suggested that the 5'LS BPs inhibited AT1 receptor translation. Our data therefore indicate that hormonal regulation of AT1 receptors involves modulation of 5'LS BPs by estrogen. These findings may in part account for the observed protective effects of estrogen on cardiovascular disease.
authors.affiliation: Department of Physiology and Biophyscis, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: K
authors.initials: K
authors.lastname: Krishnamurthi
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: L B
authors.initials: LB
authors.lastname: Clerch
authors.forename: K
authors.initials: K
authors.lastname: Sandberg
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D014599:Uterus / Q000378:metabolism
chemical_list: D004967:Estrogens; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D004958:Estradiol