This research proposal is designed to continue our investigation of the interactions between the principle mammalian calcium regulating hormones, namely vitamin D and PTH. We plan to do a thorough study on the effects of various D metabolites, in particular 24,25 dihydroxycholecalciferol (24,25DHCC) on PTH secretion. Other major calciferals to be tested are D3, 25 hydroxycholecalciferol 25 hydroxycholecalciferol (25HCC) and 1,25 dihydroxycholecalciferol (1,25DHCC). The preliminary data would suggest that dietary calcium has a profound effect on the suppressive effects of 24,25DHCC on PTH secretion. We propose that the parathyroid glands of animals maintained on a normal calcium diet are suppressed by 24,25DHCC so that the concentration of biologically active PTH in serum in decreased. Conversely, we suggest that the parathyroid gland in animals on a severely restricted calcium intake are not affected by 24,25DHCC. We propose that the ability of specific receptors for this metabolite in the parathyroid glands may be regulated in some way by calcium intake. We propose a series of in vivo, in situ and in vitro experiments to test this hypothesis. Both acute and chronic studies are planned. We plan to test this metabolite and others, at various concentrations of metabolites and time. We plan to evaluate the effects of 25,26 DHCC, the Beta-Lactone, the trihydroxy vitamin D metabolite 1,24,25 THCC in addition to D3, 25HCC, 24, 25DHCC and 1,25DHC for their effects on PTH secretion. We wish to examine the secretory products of the parathyroid glands under influence of various D metabolites. Both in situ and in vitro studies will be performed. Fractionation of the samples will be done on Bio gel and HPLC chromatography and the eluates examined by sequence specific radioimmunoassay and the cytochemical bioassay for PTH. We plan to investigate what if any effects the various vitamin D metabolites have on the metabolism of PTH. And lastly, we plan initial investigations into the mechanisms by which PTH secretion is affected by Vitamin D.
