The purposes of this project are to: I Further characterize the neurotransmitter regulation of ACTH release and the level at which it occurs (ie, CNS or pituitary) by: (A) Investigating (in the rat) the interrelations between the development of circadian periodicity of plasma corticosteroid levels, stress evoked corticosteroid release, and elevated corticosteroid levels, and that of regional CNS content and turnover of acetylcholine. (B) The study (in dispersed pituitary cell preparations) of the direct effect of monoaminergic and cholinergic agents on ACTH release. II Investigate (by immunoassay and bioassay) the nature of ACTH released: (A) In vivo: in diseases affecting the human CNS-pituitary-adrenal axis, as well as under conditions of circadian variation, stress and feedback in both normal subjects and patients with pituitary and adrenal disease. (B) In vitro: in response to hypothalamic extracts and neurotransmitter agents. III Further study the circadian periodicity of plasma ACTH and corticosteroid levels to determine in animals, whether temporary obliteration of such periodicity hastens its phase shifting. IV Study the effect of somatostatin on pituitary ACTH release, in view of its reported suppressive effects on other peptide hormones. V Continue studies of the effect of cyproheptadine in the treatment of Cushing's disease and Nelson's syndrome. BIBLIOGRAPHIC REFERENCES: Krieger, D.T., Luria, M. Plasma ACTH and Cortisol Responses to TRF, Vasopressin or Hypoglycemia in Cushing's Disease and Nelson's Syndrome. J. Clin. Endo. Metab. 44: 131-138, 1977. Krieger, D.T. CRF Distribution in Normal and Brattleboro Rat Brain, and Effect of Deafferentation, Hypophysectomy and Steroid Treatment in Normal Animals. Endocrinology, 100:227-237, 1977.