Biomedical Engineering Reference
In-Depth Information
1.6.2 Vitamin D
Vitamin D, or calcitriol, is a steroid hormone that has long been known
for its important role in regulating body levels of calcium and phospho-
rus, and in the mineralization of bone. More recently, it has become clear
that receptors for vitamin D are present in a wide variety of cells, and that
this hormone has biological effects that extend far beyond the control of
mineral metabolism. Vitamin D is carried in the bloodstream to the liver,
where it is converted into the prohormone calcidiol. Circulating calcidiol
may then be converted into calcitriol, the biologically active form of vita-
min D, either in the kidneys or by monocyte-macrophages in the immune
system. Calcitriol mediates its biological effects by binding to vitamin D
receptors (VDRs), which are principally located in the nuclei of target cells.
The binding of calcitriol to the VDR allows the VDR to act as a transcrip-
tion factor that modulates the gene expression of transport proteins (such
as TRPV6 and calbindin), which are involved in calcium absorption in the
intestine.
In fact, vitamin D is well known as a hormone involved in mineral metab-
olism and bone growth. Its most dramatic effect is to facilitate intestinal
absorption of calcium, although it also stimulates absorption of phosphate
and magnesium ions. In the absence of vitamin D, dietary calcium is not
absorbed at all efficiently. Vitamin D stimulates the expression of a number
of proteins involved in transporting calcium from the lumen of the intestine,
across the epithelial cells, and into blood. The best studied of these calcium
transporters is calbindin, an intracellular protein that ferries calcium across
the intestinal epithelial cell.
Numerous effects of vitamin D on bone have been demonstrated. As a
transcriptional regulator of bone matrix proteins, it induces the expres-
sion of osteocalcin and suppresses the synthesis of type I collagen. In cell
cultures, vitamin D stimulates differentiation of osteoclasts. However,
studies of humans and animals with vitamin D deficiency or mutations in
the vitamin D receptor suggest that these effects are perhaps not of major
physiologic importance, and that the crucial effect of vitamin D on bones is
to provide the proper balance of calcium and phosphorus to support min-
eralization. It turns out that vitamin D receptors are present in most if not
all cells in the body. Additionally, experiments using cultured cells have
demonstrated that vitamin D has potent effects on the growth and differ-
entiation of many types of cells. These findings suggest that vitamin D has
physiologic effects much broader than just a role in mineral homeostasis
and bone function.
1.6.3 Calcitonin
Calcitonin is a hormone known to participate in calcium and phospho-
rus metabolism. In mammals, the major source of calcitonin is from the
