Molecular basis for the regulation of the nuclear receptor LRH-1

Liver receptor homolog-1 (LRH-1) is a nuclear receptor (NR) with diverse functions in development, differentiation and metabolism and has been extensively studied in the enterohepatic system. While initially described as an orphan NR, recent studies suggest that specific phospholipids act as endogenous LRH-1 ligands. Although binding of ligands may enhance its transcriptional activation, posttranslational modifications (PTMs) and binding of coregulators and other NRs have emerged as mechanisms to fine-tune the selective regulation of LRH-1 target genes. In this review article, we will discuss how LRH-1 is regulated by PTMs and binding of ligands and coregulators, and explain some metabolic consequences with a special focus on liver physiology.