Endocrine disruption via estrogen receptors that participate in nongenomic signaling pathways

Cheryl S. Watson, Yow Jiun Jeng, Jutatip Guptarak

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

When inappropriate (non-physiologic) estrogens affect organisms at critical times of estrogen sensitivity, disruption of normal endocrine functions can result. Non-physiologic estrogen mimetics (environmental, dietary, and pharmaceutical) can signal rapidly and potently via the membrane versions of estrogen receptors, as can physiologic estrogens. Both physiologic and non-physiologic estrogens activate multiple signaling pathways, leading to altered cellular functions (e.g. peptide release, cell proliferation or death, transport). Xenoestrogens' mimicry of physiologic estrogens is imperfect. When superimposed, xenoestrogens can alter endogenous estrogens' signaling and thereby disrupt normal signaling pathways, leading to malfunctions in many tissue types. Though these xenoestrogen actions occur rapidly via nongenomic signaling pathways, they can be sustained with continuing ligand stimulation, combinations of ligands, and signaling that perpetuates downstream, eventually also impinging on genomic regulation by controlling the activation state of transcription factors. Because via these pathways estrogens and xenoestrogens cause nonmonotonic stimulation patterns, they must be carefully tested for activity and toxicity over wide dose ranges. Nongenomic actions of xenoestrogens in combination with each other, and with physiologic estrogens, are still largely unexplored from these mechanistic perspectives.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume127
Issue number1-2
DOIs
StatePublished - Oct 2011

Fingerprint

Estrogen Receptors
Estrogens
Ligands
Cell proliferation
Cell death
Toxicity
Cell Death
Transcription Factors
Chemical activation
Cell Proliferation
Tissue
Membranes
Peptides
Pharmaceutical Preparations

Keywords

  • Estrogens
  • Nongenomic
  • Nonmonotonic
  • Receptors
  • Women's health
  • Xenoestrogens

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Endocrine disruption via estrogen receptors that participate in nongenomic signaling pathways. / Watson, Cheryl S.; Jeng, Yow Jiun; Guptarak, Jutatip.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 127, No. 1-2, 10.2011, p. 44-50.

Research output: Contribution to journalArticle

Watson, Cheryl S. ; Jeng, Yow Jiun ; Guptarak, Jutatip. / Endocrine disruption via estrogen receptors that participate in nongenomic signaling pathways. In: Journal of Steroid Biochemistry and Molecular Biology. 2011 ; Vol. 127, No. 1-2. pp. 44-50.
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