Estrogen receptor-related receptor alpha: a mediator of estrogen response in bone

J Clin Endocrinol Metab. 2005 May;90(5):3115-21. doi: 10.1210/jc.2004-2168. Epub 2005 Feb 15.


Estrogen receptor-related receptor-alpha (ERRalpha) is an orphan nuclear receptor with sequence homology to the estrogen receptors, ERalpha/beta, but it does not bind estrogen. However, several recent studies suggest that ERRalpha not only plays a functional role in osteoblasts but also impinges on the estrogen axis in bone, as it does in at least certain other estrogen target tissues. We summarize here data on ERRalpha and its cellular and molecular modes of action that have broad implications for considering the potential role of this orphan receptor as a new therapeutic target in osteopenic disorders such as osteoporosis as well as other estrogen-responsive conditions.

Publication types

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

MeSH terms

  • Aromatase / genetics
  • Bone and Bones / drug effects*
  • Bone and Bones / physiology
  • Estrogens / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type III
  • Osteogenesis
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Estrogen / physiology*


  • ERRalpha estrogen-related receptor
  • Estrogens
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Aromatase