ENDOGENOUS RETINOID-X RECEPTORS CAN FUNCTION AS HORMONE RECEPTORS IN PITUITARY-CELLS

Retinoids regulate gene transcription by interacting,vith both retinoi c acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since un liganded RXRs can act as heterodimerization partners for RARs and othe r nuclear hormone receptors, it is unclear whether ligand binding by R XRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolyt ic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carc inoma cells, even though it activated transcription of an RXR-responsi ve reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR- specific ligand induced rat growth hormone mRNA in GH3 pituitary cells , indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Ou r results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-depe ndent regulators of gene expression, i.e., classical nuclear hormone r eceptors.