This project is designed to determine how the lactotroph cell perceives dopamine as both a prolactin-inhibiting hormone and a prolactin-releasing hormone. This will be accomplished by pursuing 5 specific aims. In the first aim, we will determine the role of dose, temperature and pattern of administration on the stimulatory or inhibitory effects of dopamine on prolactin secretion in vitro. In the second specific aim we will determine with the reverse hemolytic plaque reaction if the cell types which are responding in this dual manner to dopamine are exclusively lactotrophs and/or somatomammotrophs. In the third aim we will characterize the nature of the intracellular mechanisms responsible for both the stimulatory and inhibitory response to dopamine. In the fourth aim we will characterize the interaction of known stimulators of prolactin with the inhibitory and stimulatory response to dopamine. In the fifth aim we will determine how the rat uses the stimulatory properties of dopamine in controlling prolactin secretion in various physiological situations. These experiments will use techniques already established in our laboratories to answer physiological questions of importance to all mammals known to use dopamine as a neurohormone which controls prolactin secretion. In addition, these studies may suggest strategies through which clinicians might wish to control prolactin secretion.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Endocrinology Study Section (END)
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Florida State University
Schools of Arts and Sciences
United States
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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
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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
Sirzen-Zelenskaya, A; Gonzalez-Iglesias, A E; Boutet de Monvel, J et al. (2011) Prolactin induces a hyperpolarising current in rat paraventricular oxytocinergic neurones. J Neuroendocrinol 23:883-93
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

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