Expression of genes encoding neuropeptides and enzymes in the brain, with emphasis on the hypothalamus, are being studied. We isolated the rat vasopressin and oxytocin genes and are continuing our transgenic mice experiments (that enabled expression of oxytocin in a tissue and physiologically specific fashion) with promoter-mutated transgenes. We are also studying the novel EM protein, RHS2 (Brain-4) whose full-length cDNA we cloned last year. We are pursuing double simultaneous in situ hybridization studies to determine potentially regulated genes. We are also mapping the sites of expression of the four class III POU proteins to further our understanding of their roles, especially in advance of initiated homologous recombination studies. We have mapped the sites of expression during development of the four thyroid hormone receptor subtypes and identified sites of action responsible for defects encountered in fetal thyroid hormone deprivation. We have also examined the sites of expression of two vasopressin and two somatostatin receptor subtypes and are currently analyzing these data. Mapping of gene expression in the human hypothalamus continues, with analysis of vasopressin, oxytocin, and LHRH completed with opioids and tachykinins in progress. Regulation of galanin expression in the paraventricular and supraoptic nuclei by the arcuate nucleus is being studied through the use of monosodium glutamate, a toxin.