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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043200-10
Application #
6517202
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Sato, Sheryl M
Project Start
1992-05-01
Project End
2004-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
10
Fiscal Year
2002
Total Cost
$250,778
Indirect Cost
Name
Florida State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
020520466
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
Duncan, Peter J; Tabak, Joël; Ruth, Peter et al. (2016) Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of Male Murine Anterior Pituitary Corticotrophs. Endocrinology 157:3108-21
Helena, Cleyde V; Toporikova, Natalia; Kalil, Bruna et al. (2015) KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats. Endocrinology 156:4200-13
Corthell, J T; Stathopoulos, A M; Watson, C C et al. (2013) Olfactory bulb monoamine concentrations vary with time of day. Neuroscience 247:234-41
Szawka, Raphael E; Poletini, Maristela O; Leite, Cristiane M et al. (2013) Release of norepinephrine in the preoptic area activates anteroventral periventricular nucleus neurons and stimulates the surge of luteinizing hormone. Endocrinology 154:363-74
Chu, Z; Tomaiuolo, M; Bertram, R et al. (2012) Two types of burst firing in gonadotrophin-releasing hormone neurones. J Neuroendocrinol 24:1065-77
Tabak, Joël; Tomaiuolo, Maurizio; Gonzalez-Iglesias, Arturo E et al. (2011) Fast-activating voltage- and calcium-dependent potassium (BK) conductance promotes bursting in pituitary cells: a dynamic clamp study. J Neurosci 31:16855-63
Watts, Margaret; Tabak, Joel; Bertram, Richard (2011) Mathematical modeling demonstrates how multiple slow processes can provide adjustable control of islet bursting. Islets 3:320-6
Helena, Cleyde V; Cristancho-Gordo, Ruth; Gonzalez-Iglesias, Arturo E et al. (2011) Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol 301:R676-81
Tabak, Joel; Rinzel, John; Bertram, Richard (2011) Quantifying the relative contributions of divisive and subtractive feedback to rhythm generation. PLoS Comput Biol 7:e1001124
Teka, Wondimu; Tabak, Joel; Vo, Theodore et al. (2011) The Dynamics Underlying Pseudo-Plateau Bursting in a Pituitary Cell Model. J Math Neurosci 1:

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