EXPRESSION OF NUCLEAR HORMONE RECEPTORS IN THE RAT SUPRAOPTIC NUCLEUS

To investigate the role of nuclear hormone receptors on neuropeptide g ene expression in the hypothalamo-neurohypophyseal system (HNS) of the rat, a survey was made of members of the nuclear hormone receptor sup erfamily that are expressed in the supraoptic nucleus (SON). A polymer ase chain reaction cloning strategy based on homologies in the DNA-bin ding domain of AGGTCA-binding factors was devised for the identificati on of receptors in microdissected SON tissue. Cloning of the amplified products led to the identification of five true receptors, thyroid ho rmone receptor-alpha (THR alpha), retinoic acid receptor-alpha, retino ic acid receptor-gamma, retinoid X receptor-alpha, and retinoid X rece ptor-gamma, as well as four orphan receptors, apolipoprotein AI regula tory protein (ARP-1), chicken ovalbumin upstream promoter transcriptio n factor I (COUP-TF I), estrogen-related receptor 2, and testis recept or 4 (TR4). Dot-blot screening of amplified gene fragment analysis sho wed that THR alpha, ARP-1, TR4, and COUP-TF I were the most abundant f actors expressed in the SON region, in the order THR alpha > ARP-1 > T R4 approximate to COUP-TF I. THR alpha has previously been localized t o HNS neurons. In situ hybridization analysis showed that ARP-1, COUP- TF I, and TR4 were not expressed in magnocellular neurons at appreciab le levels, but rather in surrounding structures. Furthermore, in lacta ting female rats there were no significant differences in the composit ion of the nine identified nuclear hormone receptors in the SON region compared with control animals. From these experiments, it is conclude d that there is a multitude of hypothalamically expressed nuclear horm one receptors, but that only THR(alpha is expressed at relatively high abundance in HNS neurons. This indicates that the peptide-producing m agnocellular neurons of the SON express a specific set of transcriptio n factors of the nuclear hormone receptor family.