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Estradiol induces proliferation of keratinocytes via receptor‐ mediated mechanisms
Author(s) -
Verdier-Sevrain S.,
Yaar M.,
Cantatore J.,
Traish A.,
Gilchrest B. A.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1088fje
Subject(s) - estrogen receptor , receptor , estrogen , signal transduction , microbiology and biotechnology , keratinocyte , cell growth , estrogen receptor beta , estrogen receptor alpha , chemistry , medicine , biology , endocrinology , cell culture , biochemistry , genetics , cancer , breast cancer
In this study, we investigated the effects of estradiol on the proliferation of neonatal keratinocytes, the expression of estrogen receptor isoforms, and the signaling mechanisms by which estradiol mediates cell growth. We demonstrate that estradiol binds neonatal keratinocytes with high affinity ( K d =5.2nM) and limited capacity (B max of 14.2fmol/mg of protein), confirming the presence of estrogen binding sites. Using specific antibodies, we demonstrate that keratinocytes express both estrogen receptor (ER)‐α and ER‐β. At physiological concentrations, estradiol up‐regulates the level of ER‐α receptors in keratinocytes and induces keratinocyte proliferation. The proliferative effect of estradiol requires the availability of functional estrogen receptors, as it is abrogated by anti‐estrogen administration. Estradiol effect on keratinocyte proliferation is most likely mediated in part by activation of a nongenomic, membrane‐ associated, signaling pathway involving activation of the extracellular signal regulated kinases 1 and 2 and in part by the genomic signaling pathway through activation of nuclear receptors.