This research seeks to further elucidate the role of tuberoinfundibular dopaminergic (TIDA) neurons in the release of prolactin (PRL) and luteinizing hormone (LH) from the anterior pituitary gland in the rat. Sensitive neurochemical assays combined with a microdissection method allow for the measurement of changes in neurotransmitter and LH-RH function in discrete nuclei, fiber pathways and terminal projection fields of the rat brain. The neuronal activity of TIDA terminals in the medial (MEm) and lateral (MEl) median eminence will be contrasted with each other and with other known dopaminergic and noradrenergic projections during controlled endocrine manipulations of PRL and LH secretion. Changes specific to TIDA neurons may thus be identified and correlated with PRL and LH titers in the peripheral circulation. Neuronal activity will be assessed by five indices: (1) the determination of dopamine (DA) and norepinephrine (NE) turnover, (2) measurement of catecholamine metabolites, (3) determination of DA and LH-RH in portal blood, (4) 3H-2-deoxy-glucose autoradiography, and (5) the use of median eminence synaptosome preparations to study compounds which modulate DA and LH-RH release. An analysis of the suckling-induced rise in PRL will be undertaken entailing estimation of TIDA neuronal activity in the MEm and MEl during this dramatic neuroendocrine response. A quantitative and time course study of the short-loop negative feedback action of PRL on TIDA neurons will be performed. The role of TIDA neurons in the Beta-endorphin-induced increase and 2-brom-Alpha-ergocriptine (CB-154)-induced decrease in PRL secretion will be studied. The effects of hyperprolactinemia on hypothalamic mechanisms involved in LH release will be studied in intact, castrated and steroid replaced male and female rats, in lactating rats and in the cycling rat. These complimentary models provide controlled endocrine environments in which to examine the effect of either endogenous PRL hypersecretion, or exogenously administered PRL, on the LH-RH release mechanism. These studies bear on two working hypotheses: (1) that TIDA neurons function as prolactin inhibitory factor (PIF) neurosecretory neurons and (2) that only the TIDA neurons projecting to the MEm function as PIF neurons while those terminating in the MEl are inhibitory neuromodulators of LH-RH release.
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