Neurotensin and Neuroendocrine Regulation

More than two decades of research indicate that the peptide neurotensin (NT) and its cognate receptors participate to a remarkable extent in the regulation of mammalian neuroendocrine systems, potentially at multiple levels in a given system. NT-synthesizing neurons appear to exert a direct or indirect stimulatory influence on neurosecretory cells that synthesize gonadotropin-releasing hormone, dopamine (DA), somatostatin, and corticotropin-releasing hormone (CRH). In addition, context-specific synthesis of NT occurs in hypothalamic neurosecretory cells located in the arcuate nucleus and parvocellular paraventricular nucleus, including distinct subsets of cells which release DA, CRH, or growth hormone-releasing hormone into the hypophysial portal circulation. At the level of the anterior pituitary, NT stimulates secretion of prolactin and occurs in subsets of gonadotropes and thyrotropes. Moreover, circulating hormones influence NT synthesis in the hypothalamus and anterior pituitary, raising the possibility that NT mediates certain feedback effects of the hormones on neuroendocrine cells. Gonadal steroids alter NT levels in the preoptic area, arcuate nucleus, and anterior pituitary; adrenal steroids alter NT levels in the hypothalamic periventricular nucleus and arcuate nucleus; and thyroid hormones alter NT levels in the hypothalamus and anterior pituitary. Finally, clarification of the specific neuroendocrine roles subserved by NT should be greatly facilitated by the use of newly developed agonists and antagonists of the peptide.