Nuclear receptors in Leydig cell gene expression and function.

Several signals, such as hormones and signaling molecules, have been identified as important regulators of Leydig cell differentiation and function. Conveying these signals and translating them into a genomic response to ensure an accurate physiological output requires the action of a network of transcription factors, including those belonging to the nuclear receptor superfamily. Nuclear receptors regulate expression of genes important for growth, differentiation, development, and homeostasis. Several nuclear receptors, such as steroid hormone receptors (NR3A and NR3C families), are activated upon ligand binding, whereas others, including members of the NR2C, NR2F, and NR4A families, either do not require a ligand or ligands have yet to be identified. Several nuclear receptors (e.g., NR2F2 and NR5A1) have been shown to play essential roles in Leydig cells, whereas for others (e.g., NR2B1 and NR4A1), the assessment of their function has been precluded by the early embryonic lethality associated with null mice or by redundancy mechanisms by other family members. This is now being overcome with the generation of novel approaches, including Leydig cell-specific knockout models. This review provides an overview of the nuclear receptor family of transcription factors as they relate to Leydig cell gene expression and function.