Non-classical mechanisms of steroid sensing in the ovary: lessons from the bovine oxytocin model

Mol Cell Endocrinol. 2014 Jan 25;382(1):466-471. doi: 10.1016/j.mce.2013.04.016. Epub 2013 Apr 28.

Abstract

Steroidogenic tissues such as the ovary, testes or adrenal glands are paradoxical in that they often indicate actions of steroid hormones within a dynamic range of ligand concentration in a high nanomolar or even micromolar level, i.e. at the natural concentrations existing within those organs. Yet ligand-activated nuclear steroid receptors act classically by direct interaction with DNA in the picomolar or low nanomolar range. Moreover, global genomic studies suggest that less than 40% of steroid-regulated genes involve classical responsive elements in gene promoter regions. The bovine oxytocin gene is a key element in the maternal recognition of pregnancy in ruminants and is regulated via an SF1 site in its proximal promoter. This gene is also regulated by steroids acting in a non-classical manner, involving nuclear receptors which do not interact directly with DNA. Dose-response relationships for these actions are in the high nanomolar range. Similar 'steroid sensing' mechanisms may prevail for other SF1-regulated genes and predict alternative pathways by which environmental endocrine disruptors might influence the functioning of steroid-producing organs and hence indirectly the steroid-dependent control of physiology and development.

Keywords: Bovine ovary; Estrogen receptor-alpha; Estrogen receptor-beta; Non-classical steroid signaling; Oxytocin; Oxytocin receptor.

Publication types

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

MeSH terms

  • Animals
  • Cattle
  • Female
  • Humans
  • Models, Biological*
  • Ovary / drug effects
  • Ovary / metabolism*
  • Oxytocin / genetics
  • Oxytocin / metabolism*
  • Signal Transduction / drug effects
  • Steroids / metabolism*
  • Xenobiotics / pharmacology

Substances

  • Steroids
  • Xenobiotics
  • Oxytocin