Journal
TOXICOLOGY LETTERS
Volume 127, Issue 1-3, Pages 217-224Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(01)00503-3
Keywords
estrogen; environmental estrogens; selective estrogen receptor
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Estrogens exert profound effects on growth, differentiation, and function of many reproductive tissues. They also affect other tissues, including bone, liver, cardiovascular system, and brain. In the last few years it has been demonstrated that several synthetic estrogens can act in a tissue-specific manner. The first example of such a selective estrogen receptor modulator (SERM) was tamoxifen, for which an estrogen agonist-like activity in the endometrium and bone was seen to occur simultaneously with an estrogen antagonist activity in the breast. The mechanisms by which the same compound can exert tissue-specific agonist and antagonist actions are still being investigated. Important aspects include the interaction of the ligand with the two estrogen receptor subtypes and the interaction of these ligand-receptor complexes with effectors, which include different DNA response elements and important coregulator proteins. In addition to well-documented effects on gene transcription, there is evidence that estrogen receptors and other estrogen binding proteins are involved in some rapid, non-genomic effects of estrogens in target cells. For these reasons it is important to point out that a toxicological evaluation of endocrine modulators should include an analysis of potential SERM-like properties. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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