Biomedical Engineering Reference
In-Depth Information
parafollicular cells in the thyroid gland, but it is also synthesized in a wide
variety of other tissues, including the lung and intestinal tract. In birds, fish,
and amphibians, calcitonin is secreted from the ultimobranchial glands.
Calcitonin is a 32 amino acid linear polypeptide hormone produced in
humans primarily by the parafollicular cells (also known as C-cells) of the
thyroid and in many other animals in the ultimobranchial body. It contains
a single disulfide bond, which causes the amino terminus to assume the
shape of a ring. Alternative splicing of the calcitonin pre-mRNA can yield
an mRNA encoding calcitonin gene-related peptide; that peptide appears to
function in the nervous and vascular systems. The calcitonin receptor has
been cloned and shown to be a member of the seven-transmembrane, G pro-
tein-coupled receptor family.
Calcitonin is formed by the proteolytic cleavage of a larger prepropep-
tide, which is the product of the CALC1 gene. The CALC1 gene belongs to
a superfamily of related protein hormone precursors including islet amy-
loid precursor protein, calcitonin gene-related peptide, and the precursor
of adrenomedullin. Calcitonin suppresses resorption of bones by inhibiting
the activity of osteoclasts, the cell type that “digests” bone matrix, releasing
calcium and phosphorus into blood.
1.6.4 Insulin-Like Growth Factor
According to Wikipedia, insulin-like growth factors (IGFs) are proteins with
high sequence similarity to insulin. IGFs are part of a complex system that
cells use to communicate with their physiologic environment. This complex
system (often referred to as the IGF “axis”) consists of two cell-surface recep-
tors (IGF1R and IGF2R), two ligands (IGF-1 and IGF-2), and a family of six
high-affinity IGF-binding proteins (IGFBP 1-6), as well as associated IGFBP
degrading enzymes, referred to collectively as proteases.
Their designation as “insulin-like” originated from experiments in which
treatment of serum with antibodies to insulin failed to eliminate all insulin
activity; the remaining activity was ultimately ascribed to the IGFs. Due to
their growth-promoting activities, they were formerly called somatomedins.
There are two principal IGFs: IGF-I and IGF-II. Each of these has a number of
variant forms, resulting from use of alternative gene promoters and alterna-
tive splicing. Structurally, both IGFs resemble insulin in having two chains
(A and B) connected by disulfide bonds. Human IGF-I and IGF-II are, respec-
tively, 70 and 67 amino acids in length.
1.6.5 Transforming Growth Factor
Transforming growth factor (sometimes referred to as tumor growth fac-
tor, or TGF) is used to describe two classes of polypeptide growth factors,
TGF-α and TGF-β. TGF-α is upregulated in some human cancers. It is pro-
duced in macrophages, brain cells, and keratinocytes, and induces epithelial
