G protein–coupled estrogen receptor: a promising therapeutic target for aldosterone-induced hypertension

Abstract

Aldosterone is one of the most essential hormones synthesized by the adrenal gland because it regulates water and electrolyte balance. G protein–coupled estrogen receptor (GPER) is a newly discovered aldosterone receptor, which is proposed to mediate the non-genomic pathways of aldosterone while the hormone simultaneously interacts with mineralocorticoid receptor. In contrast to its cardio-protective role in postmenopausal women via its interaction with estrogen, GPER seems to trigger vasoconstriction effects and can further induce water and sodium retention in the presence of aldosterone, indicating two entirely different binding sites and effects for estrogen and aldosterone. Accumulating evidence also points to a role of aldosterone in mediating hypertension and its risk factors via the interaction with GPER. Therefore, with this review, we aimed to summarize the research on these interactions to help (1) elucidate the role of GPER activated by aldosterone in the blood vessels, heart, and kidney; (2) compare the non-genomic actions between aldosterone and estrogen mediated by GPER; and (3) address the potential of GPER as a new promising therapeutic target for aldosterone-induced hypertension.

Effect of β-Estradiol on Adipogenesis in a 3T3-L1 Cell Model of Prelamin A Accumulation

“…Furthermore, Elisa Schena et al [24] have recently shown that the mineralocorticoid receptor is a new player in FPLD2. Interestingly, it has been reported that the G protein-coupled estrogen receptor (GPER) is a newly discovered aldosterone receptor, which is proposed to mediate the non-genomic pathways of aldosterone while interacting with estrogen [25]. Although this is not proof of the putative role of estrogens in modulating lamin A function on adipose tissue, it probably paves the way for future studies on this topic.…”

Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases

“…Interestingly, GPER is a newly discovered aldosterone receptor that is believed to mediate nongenomic aldosterone pathways. GPER activation by aldosterone mediates water and sodium retention in the body and contributes to vasoconstriction [220]. Recently it has been shown that production of aldosterone may be influenced by progesterone [221].…”

The renin angiotensin aldosterone system

“…These effects comprise the dilatory actions of aldosterone mediated via the endothelium (e.g., the generation of nitric oxide) and direct constrictor effects on vascular smooth muscle cells [ 13 ]. The latter is, at least in part, mediated by the newly discovered G protein–coupled estrogen receptor (GPER) [ 29 ]. The net effect of aldosterone on vascular resistance depends on the location of the specific vessel, the concentration of aldosterone, and the exposure time [ 32 ].…”