Steroid receptor coactivator-1 mediates estrogenic actions to prevent body weight gain in female mice

Endocrinology. 2013 Jan;154(1):150-8. doi: 10.1210/en.2012-2007. Epub 2012 Dec 4.


Estrogen receptor-α (ERα) expressed by hypothalamic proopiomelanocortin and steroidogenic factor-1 neurons largely mediates the antiobesity effects of estrogens in females. However, the critical molecular events that are coupled to ERα and mediate estrogenic effects on energy balance remain unknown. In the current study, we demonstrated that steroid receptor coactivator-1 (SRC1), a nuclear receptor coactivator, is abundantly expressed by both proopiomelanocortin and steroidogenic factor-1 neurons. We further showed that central administration of an ERα agonist, propyl pyrazole triol, acutely increases physical interaction between SRC1 and ERα in the hypothalamus. Finally, we demonstrated that the effects of estrogens on energy homeostasis are significantly blunted in female mice lacking SRC1 globally. Collectively our results indicate that SRC1 is functionally required to mediate the antiobesity effects of estrogen-ERα signals.

Publication types

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

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / metabolism
  • Estrogens / pharmacology*
  • Female
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Mice
  • Nuclear Receptor Coactivator 1 / genetics
  • Nuclear Receptor Coactivator 1 / metabolism*
  • Phenols
  • Pro-Opiomelanocortin / metabolism
  • Protein Binding / drug effects
  • Pyrazoles / pharmacology
  • Steroidogenic Factor 1 / genetics
  • Steroidogenic Factor 1 / metabolism*


  • Estrogen Receptor alpha
  • Estrogens
  • Phenols
  • Pyrazoles
  • Steroidogenic Factor 1
  • steroidogenic factor 1, mouse
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
  • Pro-Opiomelanocortin
  • Nuclear Receptor Coactivator 1