Estrogen receptors, phytoestrogen effect

Phytoestrogens may elicit their biological effects by binding to estrogen receptors (ERs). Until recently, only a single ER isoform, ERa, had been identified however, a second receptor termed ERp has also been identified (Enmark et al, 1997, 1999 Saunders et al, 2000, 2001). It has been shown that the ERs have different intracellular and tissue distribution patterns and are responsible for different biological effects (see Table 5.1). A number of spliced variants of both ERa and ERp have also been identified (Inoue et al, 2000 Ogawa et al, 1998 Vladusic et al, 1998). 

Phytoestrogens have similar chemical structures to estrogens and have been found to bind to estrogen receptors [Cos et al., 2003]. Therefore, there is reason to believe they will elicit estrogenic effects by similar, if not identical, mechanisms. 

Maggiolini, M. Bonofiglio,D. Marsico, S. 2001. Estrogen receptor alpha mediates the proliferative but not the cytotoxic dose-dependent effects of two major phytoestrogens on human breast cancer cells. Mol. Pharm. 60 595-602. 

There are considerable data on the chronic toxicity of NP in laboratory animals. The focus of these investigations has typically been evaluation of the potential reproductive and developmental effects of NP, due to its ability to modulate estrogen receptor-mediated responses. Many endpoints are not consistently observed across studies. Some of this variability may be due to differences in the conditions, design, and other test-specific variables of the toxicity tests. For example, since phytoestrogens are abundant in most laboratory animal feeds (such as found in soy and alfalfa) and are known to modulate estrogen receptor-mediated responses, phytoestrogens may be confounding factors as a result of the feed selection. 

Another possibility deserving consideration is that some of the phytoestrogen effects may be attributable to properties that do not involve estrogen receptors, such as effects on enzymes, protein synthesis, cell proliferation, angiogenesis, calcium transport, Na /K adenosine triphosphatase, growth factor action, vascular smooth muscle cells, lipid oxidation, and cell differentiation. Some of these properties will be further discussed. 

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