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 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.

The Characterization of AT1 Expression in the Dorsal Root Ganglia After Chronic Constriction Injury

“…This finding is in correspondence with the results obtained with nonimmuno-based methods like Angiotensin II receptor binding (Macova et al 2008), and in situ hybridization using specific riboprobes (Jöhren et al 1995). Western blot analysis using the same antibody revealed a single intensive band in the DRGs at the identical molecular weight as was found in the adrenal gland (Fig.…”

Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction

“…Binding of Ang II to the widely expressed AT 1 R plays a predominant role in the capacity of the adrenal zona glomerulosa (ZG) to produce aldosterone (Capponi 2004, Schiffrin & Touyz 2004, Hunyady & Catt 2006 via cytochrome P450 aldosterone synthase (P450aldo; Bassett et al 2004, Capponi 2004. In contrast to several adult tissues, AT 2 R is relatively highly expressed in the adult adrenal glands (ZG and medulla; Breault et al 1996, Frei et al 2001, Macova et al 2008. In various pathological situations, it is generally assumed that Ang II stimulation of the AT 2 R counteracts the effects of AT 1 R (de Gasparo et al 2000, Schiffrin & Touyz 2004.…”

Estrogen Signaling in the Adrenal Cortex

“…29 Estrogens also stimulate renin release from the juxtaglomerular cells through estrogen receptor-α (ERα), 30 whereas endogenous estrogens exert inhibitory effects on the RAAS. 28,29 Experimental studies have shown that circulating levels of aldosterone increase after menopause and that estrogen therapy blunts this increase [31][32][33][34][35] ; however, corresponding data in humans are lacking.…”

“…In line with this proposition, it was found that E2 decreases aldosterone levels and the response of aldosterone to angiotensin II in ovariectomized female rats. 33,34 Although the expression of ERβ and GPER-1 was not investigated, it could be that E2 inhibits the GPER-1-mediated secretagogue effect of E2. Moreover, ovariectomy was associated with increased BP, long-term mortality, and plasma aldosterone; the latter was prevented by E2 or phytoestrogens.…”