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 relationships in animal/human models and across a broad range of cell types, affecting multiple endpoints. The range of endpoints displaying such biphasic dose responses includes plasminogen activation, oxytocin secretion, angiogenesis, cell proliferation, bone growth, monocyte chemotaxis, secretion of various cytokines, and other effects. The quantitative features of the dose response relationships revealed that the magnitude of the stimulatory responses was typically less than twofold, whereas the stimulatory responses were markedly variable ranging from about 5- to 10(6)-fold. Mechanistic explanations of the biphasic responses are addressed.
Calabrese
E J
EJ
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst 01003, USA. edwardc@schoolph.umass.edu
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007529:Isoflavones; D009000:Monocytes / Q000502:physiology; D018919:Neovascularization, Physiologic; D010121:Oxytocin / Q000378:metabolism; D048789:Phytoestrogens; D028321:Plant Preparations; D010960:Plasminogen Activators / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D010121:Oxytocin; D010960:Plasminogen Activators