Collins and Webb reply—In no way did we intend to give the impression that estrogen receptors on the surface of plasma membranes or intracellular coupling was a new concept.

Our News & Views discussed a recent paper6 that clearly stated that the existence of a putative membrane estrogen receptor is supported by studies spanning 20 years and that the origin and functions of this receptor are not well defined. Indeed this was the main thrust of our article. We wanted to convey that the surface estrogen receptor couples to a common intracellular signaling pathway in four different cells, as illustrated in our figure. These data reinforce the rapid, non-genomic estrogen-receptor dependent mechanisms of estrogen.

It is noteworthy that the research community is expanding the function of steroid hormone receptors beyond the confines of sexual differentiation and reproductive endocrine function. Gaining a better understanding of the rapid actions of estrogen may lead to new therapeutic strategies for the treatment of cell proliferative, neurodegenerative and cardiovascular defects.