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Rapid vascular effects of estrogen and aldosterone on MAP kinase activation: A role for GPR30.
Author(s) -
Gros Robert,
Ding QingMing,
Chorazyczewski Jozef,
Feldman Ross D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.941.13
Subject(s) - gper , mapk/erk pathway , kinase , phosphorylation , estrogen receptor , microbiology and biotechnology , endocrinology , biology , signal transduction , medicine , chemistry , cancer , breast cancer
Recent studies have suggested that for EST, the rapid and non‐genomic effects may in part be mediated through the GPR30 receptor. However, the role of GPR30 in VSMC MAP kinase regulation is unclear. Therefore, we examined the role of GPR30, MR and ERa in mediating the rapid effects of EST and ALDO on ERK activation via western blotting. In native VSMCs maintained in primary culture, short‐term exposure to ALDO stimulated ERK activation (146±7% of control), whereas EST inhibited of ERK phosphorylation (62±5% of control). Both GPR30 and MR gene transfer enhanced the effect of ALDO to stimulate ERK phosphorylation (GPR30:172±10% of control; MR: 156±6% of control). Interestingly, GPR30 gene transfer reversed the effect of EST from ERK inhibition to ERK activation (149±11% of control), whereas gene transfer of ERa further inhibited ERK activation (45±6% of control). Additionally, in freshly isolated aortic tissue, which express higher endogenous levels of GPR30 (as compared to cultured VSMCs), EST exposure mediated ERK activation‐ consistent with a GPR30‐predominant effect. Overall, these data support the hypothesis that the vascular expression of GPR30 plays an important role in mediating the common and rapid vascular effects of ALDO and EST. Further, the net effect of EST to regulate ERK activation is dependent on the balance between ERα‐mediated signaling and GPR30‐mediated signaling in VSMCs.