Interplay between liganded and orphan nuclear receptors controls reproductive pathways

Nuclear receptors are transcription factors that belong to an evolutionary ancient superfamily. These proteins, which are even present in primitive me tazoans, are implicated in all levels of cell fate: proliferation, differen tiation, and apoptosis, Some of these nuclear receptors behave as ligand-in ducible transcription factors, as they have acquired during evolution the a bility to bind ligands. This is the case for some proteins that recognize s mall hydrophobic signaling molecules, and particularly the estrogen recepto r (ER or NR3A1). which regulates the target gene's transcription rate under estrogen binding. It is now known that the ER alone regulates the transcri ption of many genes, such as those implicated in reproductive functions. Ho wever, this ER-mediated signaling pathway could be modulated by other trans cription factors. Our work has established that two other orphan nuclear re ceptors (SF-1 or NR5A1 and the COUP-TFs, NR2F1 and NR2F2) can enhance two E R-regulated genes implicated in salmonid reproductive functions: the ER gen e itself, and the sGTHII beta gene. Moreover, some xenoestrogens could dist urb these regulations. Therefore, our data contribute to the concept that i nterplay between nuclear receptors is an important event for the transcript ional regulation of genes controlling cellular functions.