The mechanisms of neuroendocrine control of TSH secretion will be elucidated by studying the effects of neurotrasmitters, growth hormone, somatomedin C, thyroxine and triiodothyronine on the secretion, and biosynthesis of somatostatin and Growth Hormone Releasing Hormone (GRH) and on the rate of formation of somatostatin mRNA by liquid and in situ hybridization. Secretion will be determined in hypothalamic and cerebral cortical cells in culture, and in hypothalamic slices. Biosynthesis will be determined in these culture systems, and by intracerebral administration of amine acid precursors in intact animals undergoing changes in thyroid status, GH status, neurotransmitter agonists and antagonists, and following selective neurotoxin destruction of central serotoninergic and dopaminergic pathways. As a control for neural elements not involved in pituitary regulation, somatostatin secretion and biosynthesis will be studied in cerebral cortex and spinal cord. The possible function of VIP as a physiological regulator of prolactin secretion will be determined by study of effects of intracerebroventricular injection of anti VIP on suckling and stress induced PRL release in rats, and the possible feedback effects of PRL on VIP secretion, biosynthesis and mRNA formation will be determined in hypothalamic cells in tissue culture, and in intact animals subjected to changes in PRL secretory status. The mechanism accounting for the delayed maturation of the brain VIP systems will be determined by studying the age related changes in brain IR-VIP, and VIP mRNA, the effects of thyroid hormone on this maturation, and, in cell culture, effects of thyroid hormones, NGF, and Brain Growth Factor. To determine the role of GRH in the pathogenesis of acromegaly and idiopathic hypopituitarism by studying GH secretroy responses to GRH in patients with hypothalamic-pituitary diseases, blood and CSF levels of GRH in acromegalics, and effects of constant and intermittant injections of GRH on GH and somatostatin secretion as inferred from TSH responses to TRH.