Estrogen and related compounds: Biphasic dose responses

This article documents and quantitatively assesses the capacity of estrogen , phytoestrogens, and antiestrogens to affect biphasic dose-response relati onships in animal/human models and across a broad range of cell types, affe cting multiple endpoints. The range of endpoints displaying such biphasic d ose responses includes plasminogen activation, oxytocin secretion, angiogen esis, cell proliferation, bone growth, monocyte chemotaxis, secretion of va rious cytokines, and other effects. The quantitative features of the dose r esponse relationships revealed that the magnitude of the stimulatory respon ses was typically less than twofold, whereas the stimulatory responses were markedly variable ranging from about 5- to 10(6)-fold. Mechanistic explana tions of the biphasic responses are addressed.