Steroid Hormone Receptors

Estrogen Receptors and G proteins

Science's STKE  24 Jul 2001:
Vol. 2001, Issue 92, pp. tw2
DOI: 10.1126/stke.2001.92.tw2

Nongenomic effects of estrogen have been reported and are likely initiated by estrogen receptors (ERs) located on the plasma membrane. One such effect is the activation of endothelial nitric oxide synthase (eNOS) mediated by plasma membrane-localized ERα. Wyckoff et al. implicate the Gαi protein in mediating the signal from ERα to eNOS in immortalized endothelial cells and in transfected COS-7 cells. Estrogen-stimulated eNOS activity was inhibited by pertussis toxin and guanosine 5′-O-(2-thiodiphosphate). Estrogen stimulated the physical interaction of Gαi and ERα , which was detected by coimmunoprecipitation and was inhibited by antagonists of the ERα or pertussis toxin. The role of Gαi was substantiated by two additional experiments: (i) Gαi was overexpressed and an enhanced estrogen-stimulated eNOS activation was observed, and (ii) overexpression of the negative regulator of G-protein signaling RGS4 inhibited estrogen-stimulated eNOS activation.

M. H. Wyckoff, K. L. Chambliss, C. Mineo, I. S. Yuhanna, M. E. Mendelsohn, S. M. Mumby, P. W. Shaul, Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Gαi. J. Biol. Chem. 276, 27071-27027 (2001). [Abstract] [Full Text]