The Transcriptional Regulation of Vasopressin and Oxytocin Genes

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Vasopressin and oxytocin are closely related neuroendocrine peptide hormones synthesized in specialized neurons of the hypothalamus that project to the posterior pituitary, where they have access to the general circulation. Vasopressin is predominately involved in the physiological mechanisms of water balance and hemodynamic homeostasis, whereas oxytocin regulates milk ejection during lactation and uterine smooth muscle contractions during parturition. Although these two neuropeptide hormones exhibit widely differing physiological properties, they are structurally very similar. Since oxytocin and vasopressin only differ in two of the nine amino acids, it is believed that they are derived from a common ancestral gene. However, despite the great physiological importance of these hormones, almost nothing is known about the molecular mechanisms underlying their transcriptional regulation. Dr. Sherman will describe the genetic region that contains both the vasopressin and oxytocin genes. He will concentrate on the structure and sequence of the 5, flanking regions for the vasopressin and oxytocin duplication domain which are oriented in an inverted fashion and separated by approximately 9 kb of intergenic DNA. This region may represent the vestiges of a gene duplication event. In addition, Dr. Sherman will use state-of-the-art molecular biological methodologies to elucidate possible functional and tissue- specific relationships between the vasopressin and oxytocin genes during physiological expression. Understanding the molecular events involved in the transcriptional regulation of vasopressin and oxytocin mRNA expression in the hypothalamus will lead to a better understanding of the neuronal events leading to the secretion of these hormones by neuroendocrine cells. These studies interface neuroendocrine cell biology with neuronal and endocrine mechanisms.