The article "The Nuclear Vitamin D Receptor: Biological and Molecular Regulatory Properties Revealed" by Haussler et al. (1998) provides a comprehensive review of the biological and molecular properties of the nuclear vitamin D receptor (VDR). The VDR, a member of the superfamily of nuclear receptors, plays a central role in the regulation of gene expression in response to the hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The review highlights the VDR's actions in calcium and phosphate homeostasis, bone mineralization, and remodeling, as well as its broader roles in immune, neural, epithelial, and endocrine systems. Key points include: 1. **Pathophysiology of Vitamin D**: The traditional role of vitamin D in regulating calcium and phosphate levels is discussed, including the mechanisms of vitamin D activation and the consequences of vitamin D deficiency. 2. **VDR Knockout Mice**: The creation and phenotypic effects of VDR knockout mice are described, showing that they exhibit severe bone mineralization issues, hypocalcemia, hypophosphatemia, and hyperparathyroidism. 3. **Feedback Control**: The VDR-Vitamin D complex regulates the renal production of 1,25(OH)2D3 through feedback loops, affecting parathyroid hormone (PTH) production and phosphate reabsorption. 4. **Catabolism of 1,25(OH)2D3**: The catabolic pathways of 1,25(OH)2D3, particularly the 24-hydroxylation process, are discussed, including the role of the 24-hydroxylase enzyme. 5. **Neoclassical Actions**: The VDR is shown to have additional roles beyond bone mineral homeostasis, such as immune modulation, neuroprotection, and epithelial cell maturation. 6. **Structure and Function**: The structure and function of the VDR gene and protein are detailed, including the identification of polymorphisms and their potential clinical implications. 7. **Transcriptional Mechanisms**: The mechanisms by which the VDR-Vitamin D complex activates gene transcription are explored, including the roles of DNA binding, heterodimerization, and transactivation. The review underscores the multifaceted role of the VDR in maintaining homeostasis and regulating various physiological processes, highlighting the importance of further research to understand its full potential in therapeutic applications.The article "The Nuclear Vitamin D Receptor: Biological and Molecular Regulatory Properties Revealed" by Haussler et al. (1998) provides a comprehensive review of the biological and molecular properties of the nuclear vitamin D receptor (VDR). The VDR, a member of the superfamily of nuclear receptors, plays a central role in the regulation of gene expression in response to the hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The review highlights the VDR's actions in calcium and phosphate homeostasis, bone mineralization, and remodeling, as well as its broader roles in immune, neural, epithelial, and endocrine systems. Key points include: 1. **Pathophysiology of Vitamin D**: The traditional role of vitamin D in regulating calcium and phosphate levels is discussed, including the mechanisms of vitamin D activation and the consequences of vitamin D deficiency. 2. **VDR Knockout Mice**: The creation and phenotypic effects of VDR knockout mice are described, showing that they exhibit severe bone mineralization issues, hypocalcemia, hypophosphatemia, and hyperparathyroidism. 3. **Feedback Control**: The VDR-Vitamin D complex regulates the renal production of 1,25(OH)2D3 through feedback loops, affecting parathyroid hormone (PTH) production and phosphate reabsorption. 4. **Catabolism of 1,25(OH)2D3**: The catabolic pathways of 1,25(OH)2D3, particularly the 24-hydroxylation process, are discussed, including the role of the 24-hydroxylase enzyme. 5. **Neoclassical Actions**: The VDR is shown to have additional roles beyond bone mineral homeostasis, such as immune modulation, neuroprotection, and epithelial cell maturation. 6. **Structure and Function**: The structure and function of the VDR gene and protein are detailed, including the identification of polymorphisms and their potential clinical implications. 7. **Transcriptional Mechanisms**: The mechanisms by which the VDR-Vitamin D complex activates gene transcription are explored, including the roles of DNA binding, heterodimerization, and transactivation. The review underscores the multifaceted role of the VDR in maintaining homeostasis and regulating various physiological processes, highlighting the importance of further research to understand its full potential in therapeutic applications.