Liver receptor homolog-1, an emerging metabolic modulator

Abstract

The liver receptor homolog-1 (LRH-1; NR5A2) belongs to nuclear hormone receptor superfamily, and is expressed mainly in the liver, intestine, exocrine pancreas, and ovary. It binds DNA as a monomer, and is best known as a regulator of hepatic expression of the key bile acid biosynthetic enzyme cholesterol 7alpha hydroxylase (Cyp7A1). It is also expressed in embryonic stem cells and the initial stages of embryonic development, and the very early lethality of LRH-1 knockout mice highlights its essential developmental role. Recent crystal structures of LRH-1 and its closest relative steroidogenic factor-1 (SF-1; NR5A1) identified phospholipids as potential ligands. This intriguing discovery raises the possibility of an unexpected new class of nuclear receptor signaling molecules, but the broader functional roles of LRH-1 and these new ligands remain to be established.