THE PARATHYROID GLAND AS A TARGET ORGAN FOR VITAMIN D

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The purpose of this proposal is to identify the direct effects of vitamin D on the parathyroid gland. The hypothesis is that vitamin D-related sterols modulate parathyroid hormone secretion and/or biosynthesis directly and independently of their calcemic effects. Presently available models for examining parathyroids at the cellular level are inadequate for examining chronic steroid hormone effects on glandular function; survival of cells in culture is brief and the large animals used are not suitable for in vivo manipulations before removing parathyroids. We intend to establish an animal model which allows controlled dietary management and concurrent estimations of in vivo and in vitro parathyroid gland function. We propose to examine this hypothesis with the chick, a laboratory animal uniquely suited for in vitro parathyroid studies by virtue of its large parathyroid glands. For this purpose we propose to purify avian parathyroid hormone and establish an avian PTH radioimmunoassay. We will test the hypothesis first by examining the chronic effects of various calciferols on serum concentration of parathyroid hormone in vitamin D deficient chicks. Serum PTH will be examined as a function of serum calcium to control for calcemic effects of vitamin D, as well as the serum and glandular content of these sterols. Secondly, we will investigate parathyroid gland function in vitro following the administration of calciferols to vitamin D-deficient chicks. In these studies, parathyroid hormone biosynthesis and secretion, sensitivity of the gland to extracellular calcium, and induction of vitamin D-dependent proteins shall be analyzed. This approach, with investigator-regulated in vivo conditions, will permit, for the first time, rigorous studies of a possible direct influence of vitamin D and its metabolites on the function of the gland known to be the principal regulator of extracellular calcium homeostasis.