Prolactin (pRL) is a hormone which originates in cells of the anterior pituitary gland, lactotrophs, and plays multiple physiological roles in all mammals. Not only does it promote lactation in all mammals, but it also plays a role in maternal behavior, maintenance of pregnancy as well as osmoregulation and the immune response. Dopamine (DA) is a well established physiological inhibitor of PRL secretion. It originates in cells, neurons, within a specialized area of the brain, the hypothalamus, which sends projections that terminate upon the vasculature connecting the hypothalamus with the pituitary gland. It has recently been shown that DA is also a physiological stimulator of PRL secretion. The long term objective of this application is to characterize the mechanism whereby DA has opposing physiological effects on PRL secretion. Using measurements of PRL secretion as well as intracellular transduction events, the Specific Aims of this project will be to: (1) determine which DA receptors on the lactotroph are responsible for stimulation of PRL secretion, (2) determine which G-proteins are linked to stimulation versus inhibition of PRL secretion by DA, (3) determine if the intracellular lipids are involved in the stimulation of PRL secretion by DA and (4) determine the role of calcium in DA-stimulated PRL secretion. Since PRL has so many multi- faceted roles in the physiology of the organism, it is critical for purposes of possible therapeutic approaches to diseases involving PRL that all aspects of its physiological control be clarified. For example, both benign and malignant diseases of the mammary gland are approached by manipulating pituitary PRL secretion. Thorough knowledge of the control of PRL secretion will allow other approaches to its manipulation in disease states.
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