Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5′ leader sequence of the receptor mRNA
Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5′ leader sequence of the receptor mRNA
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DOI：
10.1210/en.140.11.5435
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发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
Sandberg, K
中科院分区：
文献类型：
--
作者：
Krishnamurthi, K;Verbalis, JG;Sandberg, K
与高血压、动脉粥样硬化、充血性心力衰竭和相关心血管疾病的发病机制有关的两个最受认可的因素是肾素血管紧张素系统（RAS）和雌激素。雌激素的主要作用来自于它对 RAS 的影响。与 OVX 对照相比，去势 (OVX) 大鼠的 β-雌二醇 (E2) 替代显着降低了垂体和肾上腺中的 1 型血管紧张素 (AT(1)) 受体表达，而显着增加了子宫中的受体表达。其他证据表明雌激素对最近发现的调节 AT1 受体表达的转录后机制具有重要影响。该机制由识别受体 mRNA 的 5' 前导序列 (5'LS) 的胞质 RNA 结合蛋白 (BP) 组成。这些 5'LS BP 的活性由雌激素以与 AT(1) 受体调节相反的方式调节。此外，小麦胚芽裂解物的体外翻译测定表明，5'LS BP 抑制 AT(1) 受体翻译。因此，我们的数据表明 AT(1) 受体的激素调节涉及雌激素对 5'LS B1 的调节。这些发现可能部分解释了观察到的雌激素对心血管疾病的保护作用。
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 (AT(1)) 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 AT(1) receptor regulation. Moreover, in vitro translation assays in wheat germ lysates suggested that the 5'LS BPs inhibited,AT(1) receptor translation. Our data therefore indicate that hormonal regulation of AT(1) receptors involves modulation of 5'LS Bl's by estrogen. These findings may in part account for the observed protective effects of estrogen on cardiovascular disease.