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Abstract
The steroid hormone estrogen acts both through nuclear receptors that control transcription of target genes and through signaling pathways outside the nucleus. Revankar et al. (see the Perspective by Hewitt et al. ) report that a G protein-coupled receptor located in the membrane of the endoplasmic reticulum mediates estrogen signaling in various cell types. Upon binding to estrogen, the receptor stimulates mobilization of intracellular calcium and synthesis of nuclear phosphatidylinositol 3,4,5-trisphosphate, both of which trigger further signaling events. Estrogen is a membrane-permeable molecule, and it is likely that its access to intracellular membrane receptors can facilitate some of the rapid nongenomic signaling initiated by the hormone. C. M. Revankar, D. F. Cimino, L. A. Sklar, J. B. Arterburn, E. R. Prossnitz, A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307 , 1625-1630 (2005). [Abstract] [Full Text] S. C. Hewitt, B. J. Deroo, K. S. Korach, A new mediator for an old hormone? Science 307 , 1572-1573 (2005). [Summary] [Full Text]
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