Nongenomic signaling pathways of estrogen toxicity.
Xenoestrogens can affect the healthy functioning of a variety of tissues by acting as potent estrogens via nongenomic signaling pathways or by interfering with those actions of multiple physiological estrogens. Collectively, our and other studies have compared a wide range of estrogenic compounds, including some closely structurally related subgroups. The estrogens that have been studied include environmental contaminants of different subclasses, dietary estrogens, and several prominent physiological metabolites. By comparing the nongenomic signaling and functional responses to these compounds, we have begun to address the structural requirements for their actions through membrane estrogen receptors in the pituitary, in comparison to other tissues, and to gain insights into their typical non-monotonic dose-response behavior. Their multiple inputs into cellular signaling begin processes that eventually integrate at the level of mitogen-activated protein kinase activities to coordinately regulate broad cellular destinies, such as proliferation, apoptosis, or differentiation.
Watson
Cheryl S
CS
Biochemistry & Molecular Biology Department, University of Texas Medical Branch, Galveston, Texas 77555-0645, USA. cswatson@utmb.edu
Jeng
Yow-Jiun
YJ
Kochukov
Mikhail Y
MY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004781:Environmental Exposure; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D015262:Xenobiotics; D020928:Mitogen-Activated Protein Kinases