LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis

Trends Cell Biol. 2004 May;14(5):250-60. doi: 10.1016/j.tcb.2004.03.008.


The liver receptor homolog-1 (LRH-1; NR5A2) and steroidogenic factor-1 (SF-1; NR5A1) are two orphan members of the Ftz-F1 subfamily of nuclear receptors. LRH-1 is expressed in tissues derived from endoderm, including intestine, liver and exocrine pancreas, as well as in the ovary. In these tissues, LRH-1 plays a predominant role in development, reverse cholesterol transport, bile-acid homeostasis and steroidogenesis. SF-1 expression is confined to steroidogenic tissues and the hypothalamo-pituitary-adrenal axis, where it is involved in the control of development, differentiation, steroidogenesis and sexual determination. In this article, we will review data concerning the structure, regulation and function of LRH-1. These data highlight structural similarities between LRH-1 and other Ftz-F1 members but also underscore important functional differences, assigning to LRH-1 a unique position among nuclear receptors.

Publication types

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

MeSH terms

  • Animals
  • Cholesterol / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Homeodomain Proteins
  • Humans
  • Ovary / physiology
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Steroidogenic Factor 1
  • Steroids / biosynthesis*
  • Structure-Activity Relationship
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • NR5A1 protein, human
  • NR5A2 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Steroids
  • Transcription Factors
  • Cholesterol