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- Martin PM, Horwitz KB, Ryan DS, McGuire WL
- Endocrinology 1978 Nov 103:5 1860-7
- Abstract
- The interactions of phytoestrogens with estrogen receptors were
studied in the human breast cancer cell line, MCF-7. The compounds
tested were coumestrol, genistein, and formononetin and the mycotoxins,
zearalenone and its reduced derivative, zearalenol. All but formononetin
compete for binding of [3H]-estradiol to unfilled cytoplasmic
estrogen receptor or unfilled nuclear estrogen receptor sites.
Relative binding affinities are zearalenol HMP (high melting point
isomer) greater than zearalenol LMP (low melting point isomer)
greater than zearalenone = coumestrol greater than genistein greater
than formononetin. Dissociation constants estimated from competition
curves show that binding affinities are high. In contrast to estradiol,
phytoestrogens bind only weakly to sex steroid-binding globulin;
they also do not bind to corticosteroid-binding globulin. These
compounds translocate the cytoplasmic estrogen receptor and bind
to unfilled nuclear estrogen receptors in whole cells. Bound nuclear
receptors are then processed in a manner similar to estradiol
in a step which rapidly decreases total cellular estrogen receptors.
The phytoestrogens are also biologically active; they can markedly
enhance tumor cell proliferation. In sum, phytoestrogens interact
with the estrogen receptors of human breast cancer cells in culture
and, therefore, may affect estrogen-mediated events in these cells.
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