• 14 DIC 19

    GPER-1 and Estrogen Receptor-β Ligands Modulate Aldosterone Synthesis


    Caroccia B1, Seccia TM, Campos AG, Gioco F, Kuppusamy M, Ceolotto G, Guerzoni E, Simonato F, Mareso S, Lenzini L, Fassina A, Rossi GP.

    Author information

    • 1Internal Medicine 4, Department of Medicine – DIMED, University of Padua, Padua, Italy;


    Fertile women have lower blood pressure (BP) and cardiovascular risk than age-matched men, which suggests that estrogens exert cardiovascular protective effects. However, whether 17 β-estradiol blunts aldosterone secretion, and thereby affects the gender dimorphism of BP, is unknown. We therefore sought for the estrogen receptor subtypes in human adrenocortical tissues ex vivo by performing gene and protein expression studies. We also investigated the effect of 17 β-estradiol on aldosterone synthesis and the involved receptors through in vitro functional experiments in the adrenocortical cells HAC15. We found that in the human adrenal cortex and aldosterone-producing adenoma cells the most expressed estrogen receptors were the estrogen receptor β (ERβ) and the G protein-coupled receptor-1 (GPER-1), respectively. After selective ERβ blockade 17 β-estradiol (10 nmol/L) markedly increased both the expression of aldosterone synthase and the production of aldosterone (+ 5-to7-fold vs baseline, p <0.001). Under the same condition the GPER-1 receptor agonist G-1 (10 nmol/L) mimicked this effect, which was abrogated by co-treatment with either the GPER-1 receptor antagonist G15, or a selective protein kinase A (PKA) inhibitor (Rp-8-Br-MB-cAMPS). Silencing of the ERβ significantly raised aldosterone synthase expression and aldosterone production. Conversely, silencing of the GPER-1 lowered CYP11B2 gene and protein expression. Moreover, it blunted the stimulatory effect of 17 β-estradiol on CYP11B2 that was seen during ERβ blockade. These results support the conclusion that in humans 17 β-estradiol inhibits aldosterone synthesis by acting via ERβ. Pharmacologic disinhibition of ERβ unmasks a potent secretagogue effect of 17 β-estradiol that involves GPER-1 and PKA signaling.

    PMID:25167221 [PubMed – as supplied by publisher]



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