Abstract 359: Modulation of Aldosterone Synthase by Estrogens: Evidence for an Interaction of Gper-1 and Estrogen B Receptors and Relevance for the Gender Dimorphism of Blood Pressure

• DOI: 10.1161/hyp.62.suppl_1.a359
• Publication Date: 2022-03-20T01:30:24Z
• Authors: Brasilina Caroccia; Teresa M Seccia; Livia Lenzini; Maniselvan Kuppusamy; Abril Gonzalez Ca...; Sara Mareso; Francesca Gioco; Ambrogio Fassina; William E Rainey; Gian Paolo P Rossi
• Keywords: GPER; Aldosterone synthase; Estrogen receptor beta

Background. Fertile women have lower blood pressure and are held to be at risk for cardiovascular events than age-matched man. However, whether this gender dimorphism involves a modulation of aldosterone synthesis by 17 beta-estradiol (E2) is unknown. Aims. i) To investigate estrogen receptor subtypes gene expression in the normal human adrenal cortex (NAC), producing adenoma (APA) adrenocortical carcinoma cell line (HAC15); ii) assess effect E2 on synthase (CYP11B2) identify involved effect. Methods. We measured alpha (ERa), beta (ERb) G protein-coupled (GPER-1)-1 NAC APA tissue, HAC15 cells real time RT-PCR. After demonstration that express ERa, ERb, GPER-1 we stimulated with 10-7M alone, or after ERb selective blockade 10-5M tetrahydrochrysenediol (THC), ERa MPP dihydrochloride (MPP), non ICI 182.780, G-15. The were also exposed agonist G-1, alone presence MPP, THC, Fulvestrant, and/or Changes CYP11B2 mRNA, RT RT-PCR, was experimental endpoint. Results. quantitative > >> ERα NAC, ERb> APA, ERb>ERa=GPER-1 cells. top antagonism did not alter expression. By contrast, significantly increased (+500 + 700% from baseline, p <0.001) antagonism, combined blockade. Likewise, G-1 markedly blockade, an abolished G15 co-treatment. Conclusion. potently stimulates via subtype activation when blocked. ERb-mediated tonic inhibition could contribute explaining both BP CV fertile increase wanes during menopause estrogen-modulation treatment.