During the requested five years of additional support we wish to continue our work on a number of related projects to elucidate the hypothalamic control of pituitary hormone release with particular emphasis on the control of prolactin (Prl), growth hormone (GH), TSH, and ACTH. This area of research will involve the following projects: (1) further purfication of the hypothalamic factors which inhibit Pr1 and stimulate Pr1 and GH release and determination of their nature; (2) further study of the mechanism of action of neurotransmitters and hypothalamic factors on the pituitary gland utilizing dispersed pituitary cells in short-term culture and purified fractions of particular pituitary cell-types; (3) further investigations of the role of the central monoaminergic, GABAergic and cholinergic systems in control of the secretion of the above pituitary hormones; (4) study of the role of brain peptides in control of Pr1, GH, ACTH and TSH; and (5) evaluation of the role of releasing and inhibiting hormones and pituitary hormones in modulating their own release and that of other releasing hormones from the hypothalamus. All of these studies will enhance our knowledge of the hypothalamic control of the adenohypophysis. They may also be of therapeutic importance in treatment of endocrine diseases and diseases of metabolism. For instance, a Pr1-inhibiting factor when synthesized and available for use could be important in suppressing metastatic breast cancers of the Pr1-dependent type and in treatment of hyperprolactinemic syndromes. Similarly a growth hormone releasing hormone may find use in control of growth in children with short stature.
