Vitamin D Functions

The classic vitamin D function is to maintain calcium (Ca) and phosphate (P) homeostasis. Its cellular effects on intestinal Ca transport are best understood (A). In the cytosol, 1,25-(OH)2-D is probably bound to a cytosol receptor before being transferred to a DNA-asso-ciated nuclear receptor. This process induces the synthesis of several proteins, such as calcium-binding protein (CaBP), an ATPase, alkaline phosphatase, phytase, etc. At the same time, lipid synthesis is increased, altering membrane lipids. The subsequent step, Ca transport from the brush border membrane to the basal membrane is not yet understood. It cannot be CaBP synthesis, which was once thought to be responsible since it is too slow to provide a sufficient explanation for a Ca transport that can be triggered within a few minutes.

Bones and kidneys are other classic target organs of vitamin D (B). In bones, the activity of osteoclasts and osteo-blasts maintains homeostasis between demineralization, i. e., the release of Ca and P, and mineralization. Because of its significance for Ca homeostasis (making Ca available to the organism), vitamin D is responsible for demineraliza-tion. Increased absorption of Ca out of the bones under the influence of 1,25-(OH)2-D is due to two factors: increased differentiation of macrophages into osteoclasts, on the one hand; and a much more rapidly occurring process, on the other hand, in which 1,25-(OH)2-D triggers osteoblasts to release an osteoclast-stimulating factor. Vitamin D's renal effects are not fully understood to date. They also serve Ca homeostasis, enhancing Ca reabsorption and P excretion in the distal renal tubules.

During recent years, further tissues and cells have been found to be responsive to 1,25-(OH)2-D (B). The present discussion centers on cellular mechanisms like the above-mentioned induction of protein synthesis, or activation of various phospholipases (C, A2, D) with subsequent second messenger formation. A 1,25-(OH)2-D-specific membrane receptor is also under consideration. Many cells respond to 1,25-(OH)2-D by releasing Ca from the intracellular pool. To what extent this constitutes a contribution to Ca homeostasis is unknown; it may simply be an intra-cellular signal. It has been observed that vitamin D deficiency and bone diseases are often accompanied by weakness of skeletal or cardiac muscle, leading to the conclusion that vitamin D may have a function in muscle cells. Today, it is assumed that 1,25-(OH)2-D activates voltage-dependent Ca channels in muscle cell membranes and is thus involved in the regulation of cross-membrane Ca transport. In the pancreas, insulin secretion is influenced by 1,25-(OH)2-D; in skin, the hormone influences growth and cell differentiation. There are also receptors for it in immune system cells, as well as various tumor cells, where 1,25-(OH)2-D usually inhibits cell proliferation.

- A. Induction of Ca Absorption

Cytoplasmic receptor

CaÙ+ Blood c ATPase Basal membrane

Cytoplasmic receptor

CaÙ+ Blood c ATPase Basal membrane

Vitamin Guide

- B. Classic and Recently Discovered Vitamin D Target Organs -

Vitamin Functions

Phospho-lipases

Immune system r-m

Inhibition of cell proliferation

Growth and differentiation

Phospho-lipases

Cytoplasmic " g^ receptor Nucleus r-m

Growth and differentiation

Ca transport

Ca and

- Classic -Kidneys —"phosphate homeostasis

Ca transport w

Bones

Ca and

- Classic -Kidneys —"phosphate homeostasis

Bones

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