Vitamin D Is Really A Hormone

Vitamin D is not strictly a vitamin since it can be synthesized in the skin, and under most conditions that is its major source. Only when sunlight is inadequate is a dietary source required. The main function of vitamin D is in the regulation of calcium absorption and homeostasis; most of its actions are mediated by way of nuclear receptors that regulate gene expression. Deficiency—leading to rickets in children and osteomalacia in adults—continues to be a problem in northern latitudes, where sunlight exposure is poor.

Vitamin D Is Synthesized in the Skin

7-Dehydrocholesterol (an intermediate in the synthesis of cholesterol that accumulates in the skin), undergoes a nonenzymic reaction on exposure to ultraviolet light, yielding previtamin D (Figure 45-3). This undergoes a further reaction over a period of hours to form the vitamin itself, cholecalciferol, which is absorbed into the bloodstream. In temperate climates, the plasma concentration of vitamin D is highest at the end of summer and lowest at the end of winter. Beyond about 40 degrees north or south in winter, there is very little ultraviolet radiation of appropriate wavelength.

Vitamin D Is Metabolized to the Active Metabolite, Calcitriol, in Liver & Kidney

In the liver, cholecalciferol, which has been synthesized in the skin or derived from food, is hydroxylated to form the 25-hydroxy derivative calcidiol (Figure 45-4). This is released into the circulation bound to a vitamin D-binding globulin which is the main storage form of the vitamin. In the kidney, calcidiol undergoes either 1-hydroxylation to yield the active metabolite 1,25-dihy-droxyvitamin D (calcitriol) or 24-hydroxylation to yield an inactive metabolite, 24,25-dihydroxyvitamin D (24-hydroxycalcidiol). Ergocalciferol from fortified foods undergoes similar hydroxylations to yield ercalcitriol.

Vitamin D Metabolism Both Regulates & Is Regulated by Calcium Homeostasis

The main function of vitamin D is in the control of calcium homeostasis, and in turn vitamin D metabolism is

regulated by factors that respond to plasma concentrations of calcium and phosphate. Calcitriol acts to reduce its own synthesis by inducing the 24-hydroxylase and repressing the 1-hydroxylase in the kidney. Its principal function is to maintain the plasma calcium concentration. Calcitriol achieves this in three ways: it increases intestinal absorption of calcium, reduces excretion of calcium (by stimulating resorption in the distal renal tubules), and mobilizes bone mineral. In addition, cal-citriol is involved in insulin secretion, synthesis and secretion of parathyroid and thyroid hormones, inhibition of production of interleukin by activated T lymphocytes and of immunoglobulin by activated B lymphocytes, differentiation of monocyte precursor cells, and modulation of cell proliferation. In its actions, it behaves like a steroid hormone, binding to a nuclear receptor protein.

Vitamin D Deficiency Affects Children & Adults

In the vitamin D deficiency disease rickets, the bones of children are undermineralized as a result of poor absorption of calcium. Similar problems occur in adolescents who are deficient during their growth spurt. Osteomalacia in adults results from demineralization of bone in women who have little exposure to sunlight, often after several pregnancies. Although vitamin D is essential for prevention and treatment of osteomalacia in the elderly, there is little evidence that it is beneficial in treating osteoporosis.

Vitamin D Is Toxic in Excess

Some infants are sensitive to intakes of vitamin D as low as 50 |g/d, resulting in an elevated plasma concen-

Calciol-25-hydroxylase ll CH2

Cholecalciferol (calciol;vitamin D3)

Calciol-25-hydroxylase ll CH2

Calcidiol

(25-hydroxycholecalciferol)

Calcidiol-1-hydroxylase

Calcidiol

(25-hydroxycholecalciferol)

Calcidiol-24-hydroxylase OH

Calcidiol-1-hydroxylase

OH

Calcidiol-24-hydroxylase OH

24-hydroxycalcidiol

Calcidiol-1-hydroxylase

24-hydroxycalcidiol

2 Calcitriol (1,25-hydroxycholecalciferol)

Calcidiol-24-hydroxylase OH

Calcidiol-24-hydroxylase OH

Calcidiol-1-hydroxylase

Calcitetrol OH

Calcitetrol OH

Figure 45-4. Metabolism of vitamin D.

tration of calcium. This can lead to contraction of blood vessels, high blood pressure, and calcinosis—the calcification of soft tissues. Although excess dietary vitamin D is toxic, excessive exposure to sunlight does not lead to vitamin D poisoning because there is a limited capacity to form the precursor 7-dehydrocholesterol and to take up cholecalciferol from the skin.

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