The proposal is based on our findings that the posterior pituitary inhibits PRL and LH, but not FSH, secretion from the anterior pituitary. Whereas the inhibition of PRL secretion is mediated by posterior lobe dopaminergic (DA) system, the mechanism by which LH is inhibited is yet unknown, but appears to involve interactions between the posterior lobe, hypothalamic GnRH and gonadal steroids. Research will proceed along three lines: 1) The role of the posterior pituitary in regulating PRL and LH secretion. a. To determine the effects of acute posterior lobectomy on PRL, LH and FSH secretion immediately before and after the proestrus surge, and to investigate possible interactions with gonadal steroids. b. To determine the long term effects of chronic posterior lobectomy on cyclicity, lactation and prepubertal maturation. 2) Dopaminergic regulation of PRL secretion. a. To measure DA secretion into hypophysial portal blood before and after posterior lobectomy. b. To compare between the activation of the hypothalamic and posterior pituitary DA and systems under conditions of altered PRL secretion by utilizing in vivo DOPA accumulation and in vitro DA biosynthesis as indices for tyrosine hydroxylase activity. c. To investigate whether the posterior lobe is independent of the hypothalamus in the production and/or secretion of DA by utilizing transplantation and lesion experiments as well as organ culture of the hypothalamo-posterior pituitary system. 3) Posterior lobe inhibition of LH secretion. a. To measure LHRH secretion into portal blood before and after posterior lobectomy. b. To determine possible changes in anterior pituitary sensitivity to exogenous GnRH after posterior lobectomy. c. To determine the ability of posterior pituitary extracts and substances known to be present in the posterior lobe to antagonize LHRH stimulation of LH secretion utilizing cultured anterior pituitary cells. This study will extend our understanding of the functional relationship between the endocrine and the nervous systems, and will contribute to better diagnosis and treatment of brain, pituitary and reproductive dysfunctions.
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