Biologic Functions of Vitamin D on Calcium Metabolism

1,25(OH)2D interacts with a specific nuclear receptor that is commonly known as the vitamin D receptor (VDR) and is one of the many members of the super family of steroid hormone receptors that includes retinoic acid, thyroid hormone, glucocorticoids, and sex steroids. Once 1,25(OH)2D interacts with the VDR, the complex forms a heterodimer with retinoic acid X receptor (RXR) (Figure 6). This new complex sits on specific segments of vitamin D responsive genes known as vitamin D responsive elements (VDREs) to either increase or decrease transcriptional activity of the vitamin D-sensitive genes such as osteocalcin, calcium binding protein (calbindin), PTH, and osteonectin (Figure 6).

In the intestine, 1,25(OH)2D enhances the absorption of dietary calcium and phosphorus across the microvilli of the small intestinal absorptive cells (Figure 5). 1,25(OH)2D also interacts with

UVB in sunlight

UVB in sunlight

Figure 3 A schematic representation of the photochemical and thermal events that result in the synthesis of vitamin D3 in the skin, and the photodegradation of previtamin D3 and vitamin D3 to biologically inert photoproducts. 7-Dehydrocholesterol (7-DHC) in the skin is converted to previtamin D3 by the action of solar ultraviolet B radiation. Once formed, previtamin D3 is transformed into vitamin D3 by a heat-dependent (AH) process. Vitamin D3 exits the skin into the dermal capillary blood system and is bound to a specific vitamin D-binding protein (DBP). When previtamin D3 and vitamin D3 are exposed to solar ultraviolet B radiation, they are converted to a variety of photoproducts that have little or no activity on calcium metabolism. (Reproduced with permission from Holick MF (1995) Vitamin D: Photobiology, Metabolism, and Clinical Applications. In: DeGroot LJ etal. (eds.) Endocrinology, 3rd edn, pp. 990-1013. Philadelphia: W.B. Saunders.)

Figure 3 A schematic representation of the photochemical and thermal events that result in the synthesis of vitamin D3 in the skin, and the photodegradation of previtamin D3 and vitamin D3 to biologically inert photoproducts. 7-Dehydrocholesterol (7-DHC) in the skin is converted to previtamin D3 by the action of solar ultraviolet B radiation. Once formed, previtamin D3 is transformed into vitamin D3 by a heat-dependent (AH) process. Vitamin D3 exits the skin into the dermal capillary blood system and is bound to a specific vitamin D-binding protein (DBP). When previtamin D3 and vitamin D3 are exposed to solar ultraviolet B radiation, they are converted to a variety of photoproducts that have little or no activity on calcium metabolism. (Reproduced with permission from Holick MF (1995) Vitamin D: Photobiology, Metabolism, and Clinical Applications. In: DeGroot LJ etal. (eds.) Endocrinology, 3rd edn, pp. 990-1013. Philadelphia: W.B. Saunders.)

monocytic stem cells in the bone marrow to initiate calcium levels by enhancing the efficiency of their transformation into mature osteoclasts intestinal calcium absorption and stimulating (Figure 5). Thus, 1,25(OH)2D3 regulates serum resorption of calcium from the bone. It remains

Previtamin D3 Skin temperature

Inert photoproducts

Previtamin D3 Skin temperature

Inert photoproducts

Vitamin D3

Diet

Intestinal

Vitamin D3

Circulation Liver I 25-OHase absorption

Circulation Liver I 25-OHase

24R-OHase^

24R-OHase^

HO

Figure 4 A schematic representation of the origin of vitamin D3 and its metabolism in the liver by the hepatic vitamin D-25-hydroxylase. Once formed, the 25-hydroxyvitamin D3 (25(OH)D3) is metabolized by either a 25(OH)D-1a-hydroxylase or a 25(OH)D-24-hydroxylase. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) can either go to its target tissues to carry out its biologic function(s), or it can be metabolized in its side-chain and degraded to calcitroic acid. (Reproduced with permission from Holick MF (1995) Vitamin D: Photobiology, Metabolism, and Clinical Applications. In: DeGroot LJ et al. (eds.) Endocrinology, 3rd edn, pp. 990-1013. Philadelphia: W.B. Saunders.)

Figure 4 A schematic representation of the origin of vitamin D3 and its metabolism in the liver by the hepatic vitamin D-25-hydroxylase. Once formed, the 25-hydroxyvitamin D3 (25(OH)D3) is metabolized by either a 25(OH)D-1a-hydroxylase or a 25(OH)D-24-hydroxylase. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) can either go to its target tissues to carry out its biologic function(s), or it can be metabolized in its side-chain and degraded to calcitroic acid. (Reproduced with permission from Holick MF (1995) Vitamin D: Photobiology, Metabolism, and Clinical Applications. In: DeGroot LJ et al. (eds.) Endocrinology, 3rd edn, pp. 990-1013. Philadelphia: W.B. Saunders.)

SUN)

Liver

Diet Vitamin D2 Vitamin D3

Major circulating form

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