The objective of the proposed research is the continued investigation of the role the hypothalamic peptides play in the regulation of secretion of the anterior pituitary gland and in control of other bodily functions. The goals of this work include: 1. The isolation from porcine hypothalamic tissue of Prolactin-Release-Inhibiting Hormone (PIF), Prolactin Releasing Hormone (PRH), an antimitogenic (growth inhibiting) factor, larger and more basic forms of CRF and other peptides with biological activities. 2. The determination of structure of these peptides. 3. The synthesis of these neurohormones and their analogs. Some peptide fragments will be also synthesized in order to determine the specificity of our RIA's for CRF and GH-RF. 4. Comparison of biological, chemical and immunological properties of porcine hypothalamic hormones with those of other species and location of structural differences, and determination of structure-activity relationship for various hypothalamic hormones. 5. Generation of antisera to these peptides for the development of radioimmunoassays and immunocytochemical localization studies. 6. Extensive physiological and biochemical studies on natural hypothalamic hormones, synthetic hormones and their synthetic analogs, including investigation of half life, metabolism and inactivation. These studies will be important for planning realistic clinical tests. An investigation of the effects of chronic administration of hypothalamic hormones on some endocrine dependent or hormone sensitive tumors will be also carried out. 7. Continued search for a follicle stimulating hormone-releasing hormone (FSH-RH) distinct from the decapeptide LH-RH (Gn-RH). 8. The investigation of the effect of hypothalamic peptides on lipid mobilization, appetite and gastric acid secretion; purification, isolation, determination of structure and synthesis of some of these peptides. 9. Providing of detailed information and ideas to clinicians on natural and synthetic materials for the planning of clinical tests on human subjects.
