Department of Experimental and Clinical Biomedical Sciences, University of Florence, 50139 Florence, Italy.
Fondazione Italiana Ricerca sulle Malattie dell'Osso (F.I.R.M.O. Onlus) Italian Foundation for the Research on Bone Diseases, 50141 Florence, Italy.
Nutrients. 2022 Mar 18;14(6):1291. doi: 10.3390/nu14061291.
Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D, as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D, and it could lead to the identification of novel therapeutic targets able to modulate these actions.
经典的固醇激素维生素 D 与钙和磷酸盐的稳态有关，并与严重营养性维生素 D 缺乏症患者的佝偻病和骨软化症的发病机制有关。近年来，人们已经扩展了已知的维生素 D 介导的作用谱。然而，这种激素如何确切地发挥其生物学功能的机制仍不完全清楚。这种代谢物与维生素 D 受体 (VDR) 的相互作用，以及随后与特定靶基因区域中维生素 D 反应元件的相互作用，导致参与钙三醇传统功能（称为基因组作用）的基因转录。此外，除了这些依赖转录的机制外，人们已经认识到生物活性形式的维生素 D 及其直接前体代谢物，即 calcifediol，通过膜受体启动快速的非基因组作用，这些受体与其他类固醇激素一样结合。到目前为止，负责介导维生素 D 代谢物快速膜反应的最佳候选物之一是膜相关 VDR (VDRm) 和蛋白二硫键异构酶家族 A 成员 3 (Pdia3)。本文的目的是概述 calcifediol 和 calcitriol 的快速非基因组作用，阐明这些作用可以提高对维生素 D 内分泌系统的理解。这将有助于更好地认识维生素 D 的生理急性功能，并可能导致识别能够调节这些作用的新治疗靶点。
