A Transmembrane Intracellular Estrogen Receptor Mediates Rapid Cell Signaling

doi:10.1126/science.1106943

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Originally published in Science Express on 10 February 2005
Science 11 March 2005:
Vol. 307. no. 5715, pp. 1625 - 1630
DOI: 10.1126/science.1106943

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A Transmembrane Intracellular Estrogen Receptor Mediates Rapid Cell Signaling

Chetana M. Revankar,¹^,2 Daniel F. Cimino,¹^,2 Larry A. Sklar,²^,3 Jeffrey B. Arterburn,⁴ Eric R. Prossnitz¹^,2^*

The steroid hormone estrogen regulates many functionally unrelatedprocesses in numerous tissues. Although it is traditionallythought to control transcriptional activation through the classicalnuclear estrogen receptors, it also initiates many rapid nongenomicsignaling events. We found that of all G protein–coupledreceptors characterized to date, GPR30 is uniquely localizedto the endoplasmic reticulum, where it specifically binds estrogenand fluorescent estrogen derivatives. Activating GPR30 by estrogenresulted in intracellular calcium mobilization and synthesisof phosphatidylinositol 3,4,5-trisphosphate in the nucleus.Thus, GPR30 represents an intracellular transmembrane estrogenreceptor that may contribute to normal estrogen physiology aswell as pathophysiology.

¹ Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
² Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
³ Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
⁴ Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA.

^* To whom correspondence should be addressed. E-mail: eprossnitz{at}salud.unm.edu

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