NEUROENDOCRINE REGULATION OF PROLACTIN SECRETION

点击翻译按钮获取中文摘要

This research seeks to further elucidate the role of tuberoinfundibular dopaminergic (TIDA) neurons in the release of prolactin (PRL) from the anterior pituitary gland in the rat. A microdissection technique has been introduced which allows for the discrete removal of nuclei, terminal projection fields and fiber pathways from the rat brain. The development of highly sensitive radioisotopic-enzymatic assays for dopamine (DA), norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) now allow for the determination of DA and NE turnover and the major DA metabolite DOPAC in such microdissected brain regions. In concert, these microtechniques allow for the neurochemical analysis of neuroendocrine events at a level of resolution far greater than previously possible. Neuronal activity will be assessed by two neurochemical indices: (1) the determination of DA and NE turnover (alpha-methyl-para-tyrosine method), and (2) measurement of DOPAC tissue concentrations. The neurochemical dynamics of TIDA terminals in the median eminence (ME) will be contrasted with other known dopaminergic projections to the caudate nucleus, olfactory tubercle and medial preoptic nucleus during controlled endocrine manipulations of PRL secretion. Changes specific to TIDA neurons may thus be identified and correlated with PRL titers in the peripheral circulation as determined by direct radioimmunoassay. A neurochemical analysis of the suckling-induced rise in PRL will be undertaken entailing estimation of TIDA neuronal activity during this dramatic neuroendocrine response. The short-loop negative feedback action of PRL on TIDA neurons will be investigated in hypophysectomized rats. A neural site of action of 2-brom-alpha-ergocryptine (CB-154), a drug used clinically to inhibit PRL secretion and in the treatment of Parkinson's disease, will be investigated at the level of the TIDA neurons. These experiments bear on the working hypothesis that TIDA neurons function as prolacting inhibitory factor (PIF) neurosecretory neurons.