Stumpf W E
International Institute of Drug Distribution, Chapel Hill, NC 27516, USA.
Histochem Cell Biol. 1995 Dec;104(6):417-27. doi: 10.1007/BF01464331.
Knowledge about sites and mechanisms of action of vitamin D and its analogs has been greatly advanced by histochemical approaches. High resolution and high sensitivity, combined with the integrative potential of relatively intact histochemical tissue preparations, contributed information that is difficult or impossible to obtain otherwise. In in vivo distribution studies with conventional biochemical assays, target cell populations associated with non-target tissues frequently remain unrecognized without the resolution achieved by cellular autoradiography. Autoradiography, alone or combined with immunohistochemistry when applied to in vivo drug targeting and target characterization, has provided information on cellular-subcellular receptor distribution in over 50 tissues. These discoveries, importantly, contribute to a new understanding of the biological role of vitamin D and challenge the concept of "the calcium homeostatic steroid hormone" as being too narrow. While some of the outstanding effects of vitamin D deficiency and toxicity relate to calcium homeostasis, the vast majority of the target tissues appear not to be primarily related to calcium metabolism, but rather to the activation and regulation of exo- and endocrine secretory and somatotrophic processes such as cell differentiation and proliferation. Also, several highly calcium-dependent tissues such as striated and smooth muscles are not genomic targets for vitamin D. The reviewed data on the diverse and extensive presence of target tissues forecast a high therapeutic potential for vitamin D and especially its low-calcemic analogs, far beyond that which is presently utilized. The evidence provided for vitamin D also testifies to the utility and need to include in vivo cytopharmacology in any target evaluation of bioactive compounds to further the understanding of their mechanisms of action, and to identify preferential targets and their differential therapeutic and toxic potentials.
组织化学方法极大地推动了对维生素D及其类似物作用部位和作用机制的认识。高分辨率和高灵敏度，再加上相对完整的组织化学组织制剂的整合潜力，提供了通过其他方式难以或无法获得的信息。在采用传统生化检测的体内分布研究中，若没有细胞放射自显影所实现的分辨率，与非靶组织相关的靶细胞群体常常无法被识别。放射自显影，单独使用或与免疫组织化学结合用于体内药物靶向和靶标表征时，已在50多种组织中提供了关于细胞 - 亚细胞受体分布的信息。重要的是，这些发现有助于对维生素D的生物学作用有新的认识，并挑战了“钙稳态甾体激素”这一概念过于狭隘的观点。虽然维生素D缺乏和毒性的一些显著影响与钙稳态有关，但绝大多数靶组织似乎并非主要与钙代谢相关，而是与外分泌和内分泌分泌以及生长激素分泌过程（如细胞分化和增殖）的激活和调节有关。此外，一些高度依赖钙的组织，如横纹肌和平滑肌，并非维生素D的基因组靶标。关于靶组织多样且广泛存在的综述数据预示着维生素D尤其是其低血钙类似物具有很高的治疗潜力，远远超过目前所利用的水平。为维生素D提供的证据也证明了在任何生物活性化合物的靶标评估中纳入体内细胞药理学的实用性和必要性，以进一步了解其作用机制，并确定优先靶标及其不同的治疗和毒性潜力。
