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Cell membrane estrogen receptors resurface

Nature Medicine volume 5, page 1330 (1999)Cite this article

To the editor—In their recent and informative News and Views "Estrogen hits the surface," Collins and Webb1 suggested that "newly discovered estrogen receptor-dependent signaling pathways demonstrate that estrogen functions in the cytosol as well as in the nucleus." Although we agree wholeheartedly with the data cited, we regret that the authors failed to acknowledge that cell surface forms of estrogen receptors coupled to intracellular signaling pathways were first reported more than 20 years ago2,3,4. Thus, this work is not so much newly discovered as rather newly recognized due to profound deficiencies in the capacity of the nuclear transcription factor concept to integrate all aspects of estrogen action.

As noted by Collins and Webb1, reports of rapid estrogen effects occurring in vasculature, breast, bone, uterus and neuronal tissues cannot be explained by prevailing theories. Yet it is still widely believed that the biological activity of estrogen in responsive cells is mediated only through a specific high-affinity estrogen receptor located exclusively in their nuclei. On binding estrogen, the nuclear receptor promotes association with target genes and permits regulation of selective gene transcription5. However, in addition to the latter pathway, it has been established that estrogen can also induce extremely rapid increases in the levels of intracellular second messengers, including calcium and cAMP, as well as activation of mitogen-activated protein kinase and phospholipase1,2,3,4. The time course of these acute events parallels that elicited by peptides, lending support to the hypothesis that they do not involve the 'classical' genomic action of estrogen. Many of the rapid effects of estrogen are now attributed to the action of the hormone at the cell membrane, and these biologic actions seem to be mediated by membrane receptors that bind estrogen. The newer literature discussed by Collins and Webb should be evaluated in the fuller context of the substantial background in this field.

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References

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Authors and Affiliations

  1. Department of Medicine-Hematology/Oncology, UCLA School of Medicine, Los Angeles, 90095-1678, California, USA

    Richard J. Pietras

  2. University of California Department of Molecular, Cell & Developmental Biology, Los Angeles, 90095-1606, California, USA

    Clara M. Szego

Authors
  1. Richard J. Pietras
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  2. Clara M. Szego
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Pietras, R., Szego, C. Cell membrane estrogen receptors resurface. Nat Med 5, 1330 (1999). https://doi.org/10.1038/70877

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