THE PARATHYROID GLAND AS A TARGET ORGAN FOR VITAMIN D

该提案的目的是确定维生素D的直接影响 甲状旁腺上。 假设维生素D相关的固醇 直接调节甲状旁腺激素分泌和/或生物合成， 独立于它们的钙效应。 现有型号 在细胞水平上检查甲状旁腺不足以检查 慢性类固醇激素对腺体功能的影响; 培养时间短，使用的大型动物不适合体内培养， 在切除甲状旁腺之前进行操作。 我们打算建立一个 动物模型，允许控制饮食管理和并发 体内和体外甲状旁腺功能的估计。 我们提出 用小鸡来检验这个假设，小鸡是一种实验室动物， 由于其较大的甲状旁腺，适合于体外甲状旁腺研究 腺体 为此，我们建议纯化禽甲状旁腺激素 建立了禽类PTH放射免疫分析方法。 我们将检验这个假设 首先通过检查各种钙化醇对血清 维生素D缺乏雏鸡的甲状旁腺激素浓度。 血清 将检查PTH作为血清钙的函数，以控制血钙 维生素D的影响，以及这些血清和腺体含量 甾醇类。 其次，我们将在体外研究甲状旁腺功能 在维生素D缺乏的小鸡服用钙化醇后。 在这些研究中，甲状旁腺激素的生物合成和分泌， 腺体对细胞外钙的敏感性，以及维生素 应分析D-依赖性蛋白。 这种方法，与 生物调节的体内条件，将首次允许， 对维生素D及其可能的直接影响的严格研究 代谢物对腺体功能的影响已知是主要的 细胞外钙稳态的调节剂。

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.