What does an orphan G-protein-coupled receptor have to do with estrogen?

Abstract

Estrogen affects multiple aspects of human physiology, including the normal growth and development of female reproductive tissues, bone integrity, cardiovascular and central nervous system functions, and plays a central role in normal mammary development and breast pathogenesis. It modulates diverse cell signaling pathways, some of which appear to be independent of the known estrogen receptors (ERs). Although many of estrogen's actions can be explained by the nuclear ERs (ER-α and ER-β) functioning as ligand-activated RNA transcription factors, there are numerous rapid biochemical and physiological responses that cannot be explained by the classical genomic effects of estrogen signaling. It has long been postulated that the rapid effects of estrogen are due to a membrane-bound ER, and two recent reports suggest that it is in fact a G-protein-coupled receptor named 'GPR30'.