Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
Best Pract Res Clin Endocrinol Metab. 2011 Aug;25(4):543-59. doi: 10.1016/j.beem.2011.05.010.
The conformationally flexible secosteroid, 1α,25(OH)₂vitamin D₃ (1α,25(OH)₂D₃) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH)₂D₃, the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH)₂D₃. By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH)₂D₃/VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection.
构象灵活的甾体 1α,25(OH)₂维生素 D₃（1α,25(OH)₂D₃）通过与维生素 D 受体（VDR）结合引发生物学反应。VDR 包含两个重叠的配体结合位点，一个是基因组口袋（VDR-GP），另一个是替代口袋（VDR-AP），分别结合碗状配体构型（基因转录）或平面状配体形状（快速反应）。当被 1α,25(OH)₂D₃占据时，VDR-GP 与视黄酸 X 受体相互作用形成异二聚体，与直接受 1α,25(OH)₂D₃控制的基因区域中的维生素 D 反应元件结合。通过招募共激活剂或核心抑制剂复合物，激活的 VDR 调节编码蛋白的基因转录，这些蛋白促进维生素 D 的传统基因组功能，包括信号肠道钙和磷酸盐吸收，以维持骨骼和钙的平衡。1α,25(OH)₂D₃/VDR 对基因表达和快速反应的控制也可延缓骨质疏松症、癌症、1 型和 2 型糖尿病、动脉硬化、血管疾病和感染等衰老相关慢性疾病的发生。
