Nongenomic signaling pathways of estrogen toxicity

Toxicol Sci. 2010 May;115(1):1-11. doi: 10.1093/toxsci/kfp288. Epub 2009 Dec 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Environmental Exposure
  • Estrogens, Non-Steroidal / chemistry
  • Estrogens, Non-Steroidal / metabolism
  • Estrogens, Non-Steroidal / toxicity*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism
  • Receptors, Estrogen / metabolism
  • Signal Transduction*
  • Structure-Activity Relationship
  • Xenobiotics / chemistry
  • Xenobiotics / metabolism
  • Xenobiotics / toxicity*

Substances

  • Estrogens, Non-Steroidal
  • Receptors, Estrogen
  • Xenobiotics
  • Mitogen-Activated Protein Kinases