[Non-genomic steroid effects: estrogen action revisited].
Estrogen receptors (ERs) are members of the nuclear receptor superfamily and act classically as transcription factors. However, it has been noted that estrogens could have early cell effects (within a few minutes) that cannot be explained by transcription activation and protein synthesis. There is now an emerging body of evidence that estrogens, like many other steroids, may cause rapid activation of signal transduction pathways. These non-genomic effects involve common second messengers, such as increased intracellular calcium levels phosphoinositide turnover or cAMP accumulation. Recent studies have also shown that estrogens can stimulate the MAP kinase signaling pathway through ERs. These effects have been observed in various estrogen target cells, including endothelial cells, osteoblasts, neurons and breast cancer cells. The ER membrane signaling pathway is thus a new component that could be taken into account to understand the complex modulation of estrogen effects in specific tissues. It could also be a new therapeutic target for the treatment of neurodegenerative, cardiovascular or breast cancer diseases.
Rouayrenc
J F
JF
Unité INSERM 540, 60, rue de Navacelles, 34090 Montpellier Cedex 5, France.
Vignon
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Bringer
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D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D011956:Receptors, Cell Surface / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D004967:Estrogens; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D004958:Estradiol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D002118:Calcium