Estrogen regulation of epithelial ion transport: Implications in health and disease

Steroids. 2012 Aug;77(10):918-23. doi: 10.1016/j.steroids.2012.02.017. Epub 2012 Mar 5.


Estrogen, 17β-estradiol (E2), has been shown to modulate the activity of ion channels in a diverse range of epithelial tissues. The channel activation or inhibition responses to E2 are often rapid, occurring in seconds to minutes, independent of protein synthesis and gene transcription ('non-genomic' response). These rapid effects of E2 require activation of specific protein kinases or changes in intracellular calcium and pH which in turn modulate the conductance, open probability or number of channels in the plasmamembrane. Estrogen has also been shown to affect the expression of ion transporters over days ('genotropic' response) causing long-term sustained changes in transepithelial ion transport. It is now accepted that so called non-genomic responses are not stand-alone events and are necessary to prime the latent genomic response and even be critical for the full latent response to occur. In a number of epithelia the non-genomic and genotropic responses to estrogen are sex-specific and variable in potency and sensitivity to E2 depending on the stage of the estrous cycle. Of increasing interest is the effect these rapid and latent actions of E2 on ion transporters have on the physiological functions of epithelia. For example, estrogen regulation of a class of voltage-gated K(+) channels (KCNQ1) can determine the rate of Cl(-) secretion in the intestine. In whole-body terms, the combined effects of estrogen on a variety of ion channels which control fluid and electrolyte transport in the kidney, intestine and lung may be necessary for endometrial expansion and implantation of the blastocyte.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis / metabolism
  • Epithelial Cells / metabolism*
  • Estradiol / physiology*
  • Estrogens / physiology*
  • Humans
  • Intestinal Mucosa / metabolism
  • Ion Transport*
  • Kidney / metabolism
  • Kidney / pathology
  • Polycystic Kidney Diseases / metabolism
  • Potassium Channels / metabolism
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • TRPV Cation Channels / metabolism


  • Estrogens
  • Potassium Channels
  • TRPV Cation Channels
  • Estradiol