This proposal deals with three main areas: the paracrine regulation of prolactin secretion by the pituitary VIP cell (of possible importance in understanding the pathogenesis of idiopathic hyperprolactinemia, a common cause of galactorrhea, amenorrhea and infertility); the secretion of a growth hormone inhibitory factor by fat cells (of possible importance in the pathogenesis of obesity); and the regulation of the brain Interleukinergic neuronal system (which may be important in neuroendocrine responses to stress, to infection, and in the pathogenesis of Alzheimer's disease, a major public health problem in our aging population).
Specific aims are: 1. To determine the role of pituitary paracrine secretion of VIP in the regulation of PRL and the factors that regulate secretion and synthesis of the intrinsic pituitary VIP system. 2. To test the hypothesis that the impaired secretion of GH in obesity is mediated by a metabolically regulated peptide secretion of fat cells that either stimulates hypothalamic somatostatin secretion or acts directly on the pituitary. 3. To determine whether the neurotrophic effects of Interleukin-1b (IL-1_ on somatostatin and somatostatin mRNA synthesis and inhibitory effects on TRH mRNA that we have observed are mediated by a direct action on neurons or via a secreted glia-derived intermediate. 4. To delineate the neuroanatomy of the central Interleukinergic system in the rat. 5. To determine whether the brain IL-system is regulated by adrenal cortical hormones, by pyrogens, by inflammation and by immunization as it is IL-1 in peripheral lymphoncytes. 6. To test the hypothesis that secretion and synthesis of the hypothalamic Interleukingergic system is regulated by classical neurotransmitters and by hormones specifically involved in stress responses.
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