5-O hole (calcidiol)


24,25-(OH)2-cholecalciferol (inactive form)

24,25-(OH)2-cholecalciferol (inactive form)

Previtamin D e i u

Cholecalciferol (calciol)


Blood Ca2+ concentration (Ionized)


(1a,25-(OH)2-cholecalciferol = active form)

cium deposition (e.g., in the kidneys). Ca2+ conc. exceeding 3.5 mmol/L lead to coma, renal insufficiency and cardiac arrhythmias.

Calcitonin (CT), or thyrocalcitonin, is a peptide hormone (32). It is mainly synthesized in the parafollicular cells (C cells) of the thyroid gland, which also contain Ca2+ sensors (^ p. 36). Hypercalcemia increases the plasma calcitonin conc. (^ D, right panel), whereas c calcitonin can no longer be detected when the .2 calcium conc. [Ca2+] falls below 2 mmol/L. Cal-^ citonin normalizes elevated serum Ca2+ conc.

mainly by acting on bone. Osteoclast activity is o. inhibited by calcitonin (and stimulated by oi PTH). Calcitonin therefore increases the up-"g take of Ca2+ by the bone—at least temporarily ™ (^ D5). Some gastrointestinal hormones accelerate calcitonin secretion, thereby enhancing o the postprandial absorption of Ca2+ by bone. i- These effects (and perhaps the restraining ef-X fect of calcitonin on digestive activities) func-i- tion to prevent postprandial hypercalcemia and the (unwanted) inhibition of PTH secretion and increased renal excretion of the just absorbed Ca2+. Calcitonin also acts on the kidneys (^ D6).

Calcitriol (1,25-(OH)2-cholecalciferol) is a lipophilic, steroid-like hormone synthesized as follows (^ C): Cholecalciferol (vitamin D3) is produced from hepatic 7-dehydrocholesterol in the skin via an intermediate product (pre-vitamin D) in response to UV light (sun, tanning lamps). Both substances bind to vitamin D-binding protein (DBP) in the blood, but cholecalciferol is preferentially transported because of its higher affinity. Previtamin D therefore remains in the skin for a while after UV light exposure (short-term storage). Cal-cidiol (25-OH-cholecalciferol) and calcitriol bind to DBP. An estrogen-dependent rise in DBP synthesis occurs during pregnancy.

Cholecalciferol (vitamin D3) is administered to compensate for inadequate UV exposure. The recommended dailydosage in children is approximately 400 units = 10 ^g; adults receive half this amount. Plant-derived ergocalciferol (vitamin D2) is equally effective as animal-derived vitamin D3. The following actions apply for both forms.

Cholecalciferol is converted to calcidiol (25292 OH-cholecalciferol) in the liver. Vitamin D is mainly stored as calcidiol because the plasma conc. of calcidiol is 25 ^g/L, and its half-life is 15 days. Calcitriol (1,25-(OH)2-cholecalciferol), the hormonally active form, is mainly synthesized in the kidneys (^ C), but also in the placenta. The plasma conc. of calcitriol is regulated by renal 1-a-hydroxylase (final step of synthesis) and by 24-hydroxylase, an enzyme that deactivates calcitriol.

The calcitriol concentration rises in response to hy-pocalcemia-related PTA secretion (^ D2), to phosphate deficiency and to prolactin (lactation). All three inhibit 24-hydroxylase and activate 1-a-hy-droxylase. It decreases due to several negative feedback loops, i.e. due to the fact that calcitriol (a) directly inhibits 1-a-hydroxylase, (b) inhibits parathyroid hormone secretion, and (c) normalizes the (decreased) plasma conc. of Ca2+ and phosphate by increasing the intestinal absorption of Ca2+ and phosphate (see below). Calcium and phosphate inhibit 1 -a-hydroxylase, while phosphate activates 24-hydroxylase.

Target organs. Calcitriol's primary target is the gut, but it also acts on the bone, kidneys, placenta, mammary glands, hair follicles, skin etc. It binds with its nuclear receptor and induces the expression of calcium-binding protein and Ca2+-ATPase (^ pp.278 and 36). Cal-citriol has also genomic effects. Calcitriol increases the intestinal absorption of Ca2+ (^ D4) and promotes mineralization of the bone, but an excess of calcitriol leads to decalcification of the bone, an effect heightened by PTH. Calcitriol also increases the transport of Ca2+ and phosphate at the kidney (^ p. 178), placenta and mammary glands.

In transitory hypocalcemia, the bones act as a temporary Ca2+ buffer (^ D) until the Ca2+ deficit has been balanced by a calcitriol-mediated increase in Ca2+ absorption from the gut. If too little calcitriol is available, skeletal demineralization will lead to osteomalacia in adults and rickets in children. Vitamin D deficiencies are caused by inadequate dietary intake, reduced absorption (fat maldigestion), insufficient UV light exposure, and/or reduced 1-a-hydroxylation (renal insufficiency). Skeletal deminer-alization mostly occurs due to the prolonged increase in parathyroid hormone secretion associated with chronic hypocalcemia (compensatory hyper-pprathhroidism).


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