The secretion of prolactin (PRL) from the anterior pituitary gland is under tonic inhibition by DA of hypothalamic origin. DA is released from three anatomically and functionally distinct hypothalamic neuronal populations: (I) periventricular hypothalamic dopaminergic (PHDA) neurons of the periventricular nucleus (A14), (II) tuberohypophysial (THDA) and (III) tuberoinfundibular (TIDA) neurons of the arcuate nucleus (A12). PHDA and THDA neurons terminate in the intermediate and neural lobes of the pituitary gland, respectively. DA, released from THDA/PHDA terminal reaches the anterior lobe through the short portal vessels, while TIDA neurons terminate in the external zone of the median eminence (ME) and supply the anterior pituitary gland with DA through the long portal vessels. All 3 DAergic neuroendocrine neuron populations exhibit similar rhythmic changes in activity during the day. However, their relative contribution and importance to the regulation of PRL secretion is not understood. Our central hypothesis is that the rhythmic activity of all 3 DAergic neuroendocrine neuron populations are paced by direct circadian input from the suprachiasmatic nucleus and contribute to the regulation of and are regulated by PRL secretion.
Three specific aims will be attacked: 1) To characterize the role of the direct suprachiasmatic input to neuroendocrine DAergic activity by conducting in vivo experiments in constant environments. Antisense antagonism will be used to verify the functional significance of the SCN input to the neuroendocrine DAergic population. 2) To characterize the feedback role of PRL in the daily activity of neuroendocrine DAergic neurons and (3) To identify the signal transduction mechanisms involved in the circadian regulation of hypothalamic neuroendocrine DAergic neurons. Results of these studies lead to a better understanding of the control of PRL secretion and hence treatment of states of infertility associated with hyperprolactinemia.
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