Page 305 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

!
cium deposition (e.g., in the kidneys). Ca conc. ex- conc. of calcidiol is 25 µg/L, and its half-life is
2+
ceeding 3.5 mmol/L lead to coma, renal insufficiency 15 days. Calcitriol (1,25-(OH) 2-cholecalciferol),
and cardiac arrhythmias. the hormonally active form, is mainly synthe-
Calcitonin (CT), or thyrocalcitonin, is a peptide sized in the kidneys (! C), but also in the
hormone (32). It is mainly synthesized in the placenta. The plasma conc. of calcitriol is regu-
parafollicular cells (C cells) of the thyroid lated by renal 1-α-hydroxylase (final step of
gland, which also contain Ca 2+ sensors synthesis) and by 24-hydroxylase, an enzyme
(! p. 36). Hypercalcemia increases the plasma that deactivates calcitriol.
calcitonin conc. (! D, right panel), whereas The calcitriol concentration rises in response to hy-
calcitonin can no longer be detected when the pocalcemia-related PTA secretion (! D2), to
Hormones and Reproduction mainly by acting on bone. Osteoclast activity is back loops, i.e. due to the fact that calcitriol (a)
calcium conc. [Ca ] falls below 2 mmol/L. Cal-
2+
phosphate deficiency and to prolactin (lactation). All
2+
conc.
citonin normalizes elevated serum Ca
three inhibit 24-hydroxylase and activate 1-α-hy-
droxylase. It decreases due to several negative feed-
inhibited by calcitonin (and stimulated by
directly inhibits 1-α-hydroxylase, (b) inhibits para-
PTH). Calcitonin therefore increases the up-
thyroid hormone secretion, and (c) normalizes the
take of Ca
by the bone—at least temporarily
2+
2+
and phosphate by
(decreased) plasma conc. of Ca
(! D5). Some gastrointestinal hormones accel-
2+
increasing the intestinal absorption of Ca
and
erate calcitonin secretion, thereby enhancing
phosphate (see below). Calcium and phosphate in-
the postprandial absorption of Ca
2+
by bone.
hibit 1-α-hydroxylase, while phosphate activates 24-
These effects (and perhaps the restraining ef-
Target organs. Calcitriol’s primary target is the
tion to prevent postprandial hypercalcemia
11 fect of calcitonin on digestive activities) func- hydroxylase.
gut, but it also acts on the bone, kidneys,
and the (unwanted) inhibition of PTH secre- placenta, mammary glands, hair follicles, skin
tion and increased renal excretion of the just etc. It binds with its nuclear receptor and in-
2+
absorbed Ca . Calcitonin also acts on the kid- duces the expression of calcium-binding pro-
neys (! D6). tein and Ca -ATPase (! pp. 278 and 36). Cal-
2+
Calcitriol (1,25-(OH) 2-cholecalciferol) is a citriol has also genomic effects. Calcitriol in-
lipophilic, steroid-like hormone synthesized creases the intestinal absorption of Ca 2+ (! D4)
as follows (! C): Cholecalciferol (vitamin D 3) and promotes mineralization of the bone, but an
is produced from hepatic 7-dehydrocholesterol excess of calcitriol leads to decalcification of
in the skin via an intermediate product (pre- the bone, an effect heightened by PTH. Cal-
vitamin D) in response to UV light (sun, tan- citriol also increases the transport of Ca 2+ and
ning lamps). Both substances bind to vitamin phosphate at the kidney (! p. 178), placenta
D-binding protein (DBP) in the blood, but and mammary glands.
cholecalciferol is preferentially transported
because of its higher affinity. Previtamin D In transitory hypocalcemia, the bones act as a tem-
therefore remains in the skin for a while after porary Ca 2+ buffer (! D) until the Ca 2+ deficit has
UV light exposure (short-term storage). Cal- been balanced by a calcitriol-mediated increase in
2+
cidiol (25-OH-cholecalciferol) and calcitriol Ca absorption from the gut. If too little calcitriol is
available, skeletal demineralization will lead to
bind to DBP. An estrogen-dependent rise in osteomalacia in adults and rickets in children. Vi-
DBP synthesis occurs during pregnancy. tamin D deficiencies are caused by inadequate di-
etary intake, reduced absorption (fat maldigestion),
Cholecalciferol (vitamin D 3) is administered to
compensate for inadequate UV exposure. The rec- insufficient UV light exposure, and/or reduced 1-α-
ommended daily dosage in children is approximately hydroxylation (renal insufficiency). Skeletal deminer-
alization mostly occurs due to the prolonged in-
400 units = 10 µg; adults receive half this amount.
Plant-derived ergocalciferol (vitamin D 2) is equally crease in parathyroid hormone secretion associated
with chronic hypocalcemia (compensatory hyper-
effective as animal-derived vitamin D 3. The following parathyroidism).
actions apply for both forms.
Cholecalciferol is converted to calcidiol (25-
292 OH-cholecalciferol) in the liver. Vitamin D is
mainly stored as calcidiol because the plasma
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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