Increasing evidence has accumulated during the past several years to implicate both releasing and inhibiting factors of hypothalamic origin in the control of the secretion of growth hormone (GH), prolactin (Prl), and thyroid stimulating hormone (TSH). As a consequence, the measurement of pituitary hormone levels alone has become insufficient to determine which of the many neuroendocrine control mechanisms are responsible for observed alterations in hormone secretion. The proposed studies will involve a continuation of our current investigative efforts 1) to clarify the control of secretion of the individual releasing and inhibiting factors: GH-releasing factor, somatostatin (SRIF), Prl-releasing factor, and Prl-inhibiting factor, as influenced by hormonal, neurotransmitter, and neuropeptidergic agents and to characterize their effects on the secretion of GH, Prl, and TSH; 2) to assess possible heterogeneity of central nervous system SRIF and thyrotropin releasing hormone (TRH) in various brain regions using multiple radioimmunoassays for each hormone which recognize different portions of the molecule along with high pressure liquid chromatographic separation techniques; 3) to study the biosynthesis of SRIF in normal brain tissue and TRH in a TRH-secreting neuroblastoma cell line; 4) to evaluate the role of the cerebrospinal fluid (CSF) in the transport and metabolism of SRIF and TRH and to assess the possible role of blood-CSF and CSF-blood transfer of these peptides; and 5) to search for releasing and inhibiting factor activity in plasma and other circulating fluids and in nonendocrine neoplastic tissues of patients with disorders of pituitary hormone secretion.