Estrogen reduces aldosterone, upregulates adrenal angiotensin II AT2 receptors and normalizes adrenomedullary Fra-2 in ovariectomized rats

Abstract

We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT 1 and AT 2 receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT 1 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 AT 1 receptor expression,decreased AT 1B receptor mRNA, and increased AT 2 receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were:normalized AT 1 receptor expression, increased AT 2 receptor expression, AT 2 receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT 1 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 AT 1 receptor downregulation and AT 2 receptor upregulation. AT 2 receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT 2 receptor upregulation and the decrease in AT 1 receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.We studied the effect of ovariectomy and estrogen replacement on expression of adrenal angiotensin II AT 1 and AT 2 receptors, aldosterone content, catecholamine synthesis, and the transcription factor Fos-related antigen 2 (Fra-2). Ovariectomy increased AT 1 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 AT 1 receptor expression, decreased AT 1B receptor mRNA, and increased AT 2 receptor expression and mRNA. Estrogen treatment decreased adrenal aldosterone content. In the adrenal medulla, the effects of estrogen replacement were: normalized AT 1 receptor expression, increased AT 2 receptor expression, AT 2 receptor mRNA, and tyrosine hydroxylase mRNA, and normalized Fra-2 expression and catecholamine content. We demonstrate that the constitutive adrenal expression of AT 1 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 AT 1 receptor downregulation and AT 2 receptor upregulation. AT 2 receptor upregulation and modulation of Fra-2 expression may participate in the estrogen-dependent normalization of adrenomedullary catecholamine synthesis in ovariectomized rats. The AT 2 receptor upregulation and the decrease in AT 1 receptor function and in the production of the fluid-retentive, pro-inflammatory hormone aldosterone partially explain the protective effects of estrogen therapy.