Aldosterone Stimulates Its Biosynthesis Via A Novel GPER Mediated Mechanism

Abstract CONTEXT: The G protein-coupled estrogen receptor (GPER) mediates an aldosterone secretagogue effect of 17β-estradiol in human HAC15 adrenocortical cells after estrogen receptor β blockade. As GPER mediates mineralocorticoid receptor-independent aldosterone effects in other cell types, we hypothesized that aldosterone could modulate its own synthesis via GPER activation. METHODS: HAC15 cells were exposed to aldosterone in presence or absence of canrenone, a mineralocorticoid receptor antagonist, and/or of the selective GPER antagonist G36. Aldosterone synthase (CYP11B2) mRNA and protein levels changes were the study endpoints. Similar experiments were repeated in strips obtained ex vivo from aldosterone-producing adenoma and in GPER-silenced HAC15 cells. RESULTS: Aldosterone markedly increased CYP11B2 mRNA and protein expression (vs untreated samples, p<0.001) in both models by acting via GPER, as these effects were abolished by G36 (p<0.01) and not by canrenone. GPER-silencing (p