Vitamin D action: lessons from VDR and Cyp27b1 null mice

Area of Science:

• Endocrinology
• Molecular Biology
• Nutritional Science

Background:

• The vitamin D endocrine system's full function remains incompletely understood a century after discovery.
• The active form of vitamin D, 1,25(OH)2D, is known to be essential for calcium absorption and skeletal homeostasis.

Purpose of the Study:

• To compare findings in VDR- and Cyp27b1-null mice with human data.
• To elucidate current understanding of the vitamin D endocrine system.
• To identify outstanding questions regarding vitamin D's roles.

Main Methods:

• Utilizing genetically modified mice with inactivated vitamin D receptor (VDR) or key metabolizing enzymes (Cyp27b1).
• Comparing experimental findings in mice with observational studies in humans.
• Analyzing the impact of 1,25(OH)2D on classical (gut, bone) and non-classical target tissues.

Main Results:

• Inactivation studies confirm 1,25(OH)2D's necessity for intestinal calcium absorption and maintenance of serum calcium, bone, and growth plate homeostasis.
• Tissue-specific gene deletion models reveal precise roles of 1,25(OH)2D in various tissues.
• Human studies link vitamin D pathway disturbances to extraskeletal diseases, including cancer, infections, autoimmune, cardiovascular, metabolic, and neurocognitive disorders.

Conclusions:

• The active form of vitamin D is indispensable for skeletal health and has widespread extraskeletal effects.
• Significant knowledge gaps persist regarding the vitamin D endocrine system's complete physiological and pathological roles.
• Further research is needed to fully understand vitamin D's impact on human health and disease.