Estrogen Regulates Angiotensin AT1 Receptor Expression via Cytosolic Proteins that Bind to the 5′ Leader Sequence of the Receptor mRNA

Krishnamurthi, Kamakshi; Verbalis, Joseph G.; Zheng, Wei; Wu, Zheng; Clerch, Linda Biadasz; Sandberg, Kathryn

doi:10.1210/endo.140.11.7242

Cited by 71 publications

(31 citation statements)

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“…Ovariectomy increased AT 1 receptor expression in the zona glomerulosa, in agreement with previous observations [20, 21, 38, 39] and in the adrenal medulla, effects reversed by estrogen treatment. In addition, estrogen treatment downregulated AT 1B receptor mRNA in the zona glomerulosa.…”

Section: Discussionsupporting

confidence: 92%

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Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Macova¹,

Armando²,

Zhou³

et al. 2008

Neuroendocrinology

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We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT₁ and AT₂ receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT₁ receptor expression in the adrenal zona glomerulosa and medulla, and decreased adrenomedullary catecholamine content and Fra-2 expression when compared to intact female rats. In the zona glomerulosa, estrogen replacement normalized AT₁ receptor expression, decreased AT_1B receptor mRNA, and increased AT₂ receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT₁ receptor expression, increased AT₂ receptor expression, AT₂ receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT₁ receptors, catecholamine synthesis and Fra-2 expression are partially under the control of reproductive hormones. Our results suggest that estrogen treatment decreases aldosterone production through AT₁ receptor downregulation and AT₂ receptor upregulation. AT₂ receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT₂ receptor upregulation and the decrease in AT₁ receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.

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Section: Discussionsupporting

confidence: 92%

“…Estrogen regulates adrenal gland function and the expression of adrenal RAS. In the adrenal gland, estrogen reduces AT 1 receptor expression, and as a consequence, Ang II-induced aldosterone secretion is decreased [20, 21]. Conversely, most of the evidence indicates that estrogen enhances adrenomedullary catecholamine synthesis [22, 23].…”

Section: Introductionmentioning

confidence: 99%

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Macova¹,

Armando²,

Zhou³

et al. 2008

Neuroendocrinology

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“…6 Although the effects of oestrogen in vitro on cardiac Ang II subtype 1 (AT 1 ) receptor expression are not known, several studies have shown an alteration in Ang II receptor expression or binding with changes in circulating oestrogen concentrations in vivo. 32 In vascular smooth muscle cells, oestrogen acts on the renin-angiotensin system at different points of the cascade: at the formation of Ang II, at the level of Ang II receptors, and on Ang II induced responses. Oestrogen has been shown to increase gene expression and plasma concentrations of angiotensinogen.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of angiotensin II induced endothelin-1 gene expression by 17- -oestradiol in rat cardiac fibroblasts

Chao

2005

Heart

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Objective: To examine whether 17-b-oestradiol (E 2 ) may alter angiotensin II (Ang II) induced cell proliferation and to identify the putative underlying signalling pathways in rat cardiac fibroblasts. Design: Cultured rat cardiac fibroblasts were preincubated with E 2 then stimulated with Ang II. [ 3 H]Thymidine incorporation and endothelin-1 (ET-1) gene expression were examined. The effect of E 2 on Ang II induced NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal regulated kinase (ERK) phosphorylation were tested to elucidate the intracellular mechanism of E 2 in proliferation and ET-1 gene expression. Results: Ang II increased DNA synthesis, which was inhibited with E 2 (1-100 nmol/l). E 2 , but not 17-aoestradiol, inhibited Ang II induced ET-1 gene expression as shown by northern blotting and promoter activity assay. This effect was prevented by co-incubation with the oestrogen receptor antagonist ICI 182 780 (1 mmol/l). E 2 also inhibited Ang II increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 mediated reporter activity. Conclusions:The results suggest that E 2 inhibits Ang II induced cell proliferation and ET-1 gene expression, partially by interfering with the ERK pathway through attenuation of ROS generation. Thus, this study provides important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of oestrogen on the cardiovascular system.

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“…17␤-estradiol benzoate (10 g/day; Sigma, St. Louis, MO) was dissolved in 0.2 ml peanut oil and injected subcutaneously every day for 15 days (unless otherwise indicated); shamoperated and ovariectomized (OVX) animals were injected subcutaneously with vehicle (0.2 ml peanut oil) as previously described (18).…”

Section: Animalsmentioning

confidence: 99%

Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats

Zheng

Ji²,

Maric³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The effects of high-sodium (HS) and normal-sodium (NS) diets on ovarian hormone modulation of mean arterial pressure (MAP) were examined in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Ovariectomy increased MAP (OVX-Sham) to a greater extent in DS rats maintained for 2 wk on a HS (22 mmHg) compared with a NS (6 mmHg) diet. Ovariectomy had no effect on MAP in DR rats on NS but did increase MAP in rats on HS (10 mmHg) diets. On HS diets, glomerular filtration rate (GFR) was 36% less in the DS-Sham than DR-Sham animals; ovariectomy increased GFR in both strains by 1.4-1.5-fold; glomerular angiotensin II type 1 receptor (AT(1)R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT(1)R densities by 1.3-fold in DR rats but had no effect in DS rats; 17beta-estradiol (E(2)) downregulated adrenal AT(1)R densities in both strains on either diet; ovariectomy reduced estrogen receptor-alpha (ER-alpha) protein expression in the renal cortex by 40-50% although renal ER-alpha expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E(2) treatment, suggesting that E(2) deficiency mediates the effects of ovariectomy on MAP, GFR, AT(1)R densities, and renal ER-alpha protein expression. In conclusion, ovariectomy-induced increases in MAP are augmented by HS diet in both strains, and this effect is not mediated by a reduction in GFR. Aberrant renal AT(1)R regulation and reduced renal ER-alpha expression are potential contributors to the hypertensive effects of E(2) deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E(2) deficient, such as postmenopausal women.

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Estrogen Regulates Angiotensin AT1 Receptor Expression via Cytosolic Proteins that Bind to the 5′ Leader Sequence of the Receptor mRNA

Cited by 71 publications

References 0 publications

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Estrogen Reduces Aldosterone, Upregulates Adrenal Angiotensin II AT<sub>2</sub> Receptors and Normalizes Adrenomedullary Fra-2 in Ovariectomized Rats

Inhibition of angiotensin II induced endothelin-1 gene expression by 17- -oestradiol in rat cardiac fibroblasts

Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats

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