Calcitrol

Calcitriol is the hormonally active form of vitamin D, specifically it is 1,25-dihydroxycholecalciferol, or 1,25(OH)₂D₃. It is produced in the kidneys via 25-hydroxyvitamin D-1α-hydroxylase by the hydroxylation of calcidiol (25-hydroxycholecalciferol). Calcitriol plays a crucial role in the regulation of calcium and phosphorus levels in the blood, essential for maintaining a healthy skeleton and teeth. It acts primarily in three areas: the intestine, bones, and kidneys, promoting absorption of calcium from the gut, reabsorption of calcium in the kidneys, and, along with parathyroid hormone, the release of calcium from bones.

Biosynthesis and Regulation

Calcitriol is synthesized from cholecalciferol (vitamin D₃), which is obtained from the diet or synthesized in the skin from 7-dehydrocholesterol under the influence of ultraviolet light. Cholecalciferol is hydroxylated in the liver to form calcidiol (25-hydroxycholecalciferol). Calcidiol is then hydroxylated in the kidneys by the enzyme 25-hydroxyvitamin D-1α-hydroxylase to form calcitriol. The synthesis of calcitriol is tightly regulated by the body's requirements for calcium and phosphorus. Increased levels of parathyroid hormone, low calcium levels, and low phosphorus levels stimulate the production of calcitriol, whereas high levels of calcium and phosphorus have the opposite effect.

Function

Calcitriol acts as a steroid hormone, binding to vitamin D receptors (VDR) in target tissues. The activated VDR then interacts with Vitamin D Response Elements (VDREs) in the DNA, modulating the expression of genes involved in calcium and phosphorus homeostasis. In the intestine, calcitriol increases the absorption of calcium and phosphorus. In the bones, it works together with parathyroid hormone to mobilize calcium and phosphorus from bone tissue, and in the kidneys, it promotes the reabsorption of calcium, thereby increasing the levels of these minerals in the blood.

Clinical Significance

Calcitriol plays a vital role in the prevention and treatment of various bone diseases, such as rickets in children and osteomalacia in adults, which result from a deficiency of vitamin D or calcium. It is also used in the management of chronic kidney disease (CKD), where the kidneys are unable to produce sufficient amounts of calcitriol, leading to disturbances in calcium and phosphorus balance. Additionally, calcitriol is used in the treatment of hypoparathyroidism, osteoporosis, and is being investigated for its potential role in the prevention and treatment of certain types of cancer.

Adverse Effects

While calcitriol is essential for maintaining healthy levels of calcium and phosphorus in the blood, excessive levels can lead to hypercalcemia (high calcium levels) and hyperphosphatemia (high phosphorus levels), which can cause various symptoms and complications including nausea, vomiting, weakness, and in severe cases, kidney damage.

Conclusion

Calcitriol, as the active form of vitamin D, plays a critical role in maintaining calcium and phosphorus balance in the body, essential for healthy bones and teeth. Its synthesis and action are finely regulated by the body to ensure mineral homeostasis. Understanding the functions and regulation of calcitriol contributes to the management of bone diseases and conditions related to calcium and phosphorus imbalances.