We have focused our research on the role of tissue lipids in the secretory processes regulating the release of prolactin and growth hormone. The turnover of phosphatidylinositol has been closely linked with prolactin release because TRH is stimulatory to both, whereas dopamine is inhibitory. An increased turnover of phosphatidylinositol is also correlated with the liberation of intracellular stores of calcium, an obligatory ion for the secretory process. These studies will be extended to determine the role of phospholipid metabolites in calcium mobilization and hormone release. Specifically, the function of diacylglycerol, arachidonate, and the leukotrienes in these processes will be examined in detail. We have preliminary evidence that stimulation of arachidonate production and release is an important event in the secretory process in normal pituitary cells, and these studies will be extended to pituitary tumor cells. We do have preliminary evidence that these tumor cells have a defect in their handling of calcium, and this leads to their refractoriness to dopaminergic inhibition. This possibility is being addressed by promoting an increase in calcium uptake through the use of maitotoxin, a calcium channel activator. We believe that we can restore the ability of dopamine to inhibit prolactin release by this agent. We speculate that the abnormally reduced handling of calcium by the tumor pituitary cells may relate to their reduced ability to produce arachidonate. This complex series of investigations is currently being implemented. (C)
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