BRAIN MONOAMINES AND LUTEINIZING HORMONE SECRETION

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The objective is to examine the neural mechanisms by which the ovarian hormones, estradiol and progesterone, regulate the secretion of luteinizing hormone (LH) from the anterior pituitary gland. The experiments will test the hypothesis that the inhibitory and stimulatory feedback actions of the ovarian hormones are mediated in part via changes in the activity of noradrenergic and adrenergic neural systems that control the neurosecretion of LH-releasing hormone (LHRH). It is proposed that estradiol and progesterone affect activity in intrahypothalamic neuronal systems, such as the endogenous opioid neuropeptides and Gamma-aminobutyric acid, which regulate catecholamine release, and of neuropeptide Y (NPY), which modulates the response of the pituitary gland to LHRH. To test this hypothesis further, discrete hypothalamic areas will be incubated understatic or perifusion conditions in vitro. The release of LHRH and NPY into the medium will be measured by radioimmunoassays, while catecholamines will be measured by radioenzymatic assay. The first group of experiments will examine the postsynaptic mechanisms, especially the involvement of the Ca++ messenger system, mediating the stimulatory effect of norepinephrine (NE), epinephrine (EPI) and NPY on LHRH release. These studies will also test whether NPY alters the response of LHRH neurons to the catecholamines. A second set of studies will examine the interaction of NPY with the catecholamines in the regulation of LHRH release, and in particular, will test whether NE or EPI stimulates the release of NPY. A third set of studies will test whether the inhibitory effects of low dosage E2 treatment in vivo on the release of LHRH in vitro is due to activation of opioid systems that depress the release of NE and NPY. Other experiments will test whether the effect of in vitro progesterone to stimulate LHRH release is mediated by increased release of NE, EPI or NPY, and whether this can be inhibited by opioid or by GABA agonists. A fourth set of studies will test further the mechanisms underlying the facilitation of LHRH-induced LH release by NPY, using dispersed anterior pituitary cells in culture.