Dopaminergic (DA) treatment of hyperprolactinemia caused by prolactin (Prl) secreting pituitary neoplasms is a striking example of successful medical management of human neoplasia. The treatment typically shrinks the tumor, reduces Prl levels and restores fertility. The cytoplasmic free calcium level has a critical role in regulating Prl secretion and that of other hormones. However, there is yet much to learn about how physiological agents like DA may regulate the cytoplasmic calcium concentration to control hormone secretion.
We aim to study calcium flux in normal and neoplastic pituitary cells under the direct influence of THREE agents with IMPORTANT effects on hormone secretion: DA, growth hormone releasing factor (GRF), and SOMATOSTATIN (SRIF). To satisfy these aims and expand our knowledge about the regulation of hormone secretion under normal and pathological conditions three important parameters of 45Ca2+ flux will be comprehensively analyzed. To study 1) 45Ca2+ uptake and 2) net flux at isotopic equilibrium, normal or neoplastic rat pituitary cells are dispersed into a single cell suspension and incubated in 45Ca2+ followed by rapid vacuum filtration and washing. Calcium flux as a function of 45Ca2+ specific activity is then calculated from the radioactivity within the cells trapped on each filter. The third parameter, 45Ca2+ efflux, is directly measured as the fractional loss from prelabeled cells using a perifusion apparatus. Regulation of calcium flux has been speculated to be the basis for DA control of Prl secretion yet this vital question has not been critically evaluated. We know that GRF is dependent in some manner on calcium to stimulate growth hormone secretion, but although important, specific details about this dependency are unknown. SRIF IS A NATURALLY OCCURRING PEPTIDE WHICH INHIBITS THE SECRETION OF GH, AS WELL AS MANY OTHER BIOLOGICALLY ACTIVE HORMONES. MODULATION OF CALCIUM FLUX BY SRIF HAS BEEN TENTATIVELY INFERRED AS ONE MECHANISM CONTRIBUTING TO ITS ACTION, BUT RIGOROUS INVESTIGATION IS LACKING. The preliminary studies are promising; the experiments are rationally organized; and the resources and environment suitable for the efficient execution of this three year program.
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