Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

V. Functions of the Thyroid Gland
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FIGURE 20-2 Chemical structures of the major iodinated compounds
of the thyroid gland.
FIGURE 20-1 Pathways of iodine metabolism and thyroid hormone
synthesis. Goitrogenic blocking agents are shown in brackets.
A . Thyroid Hormones
The principal thyroid hormones elaborated by the thyroid
are the two active hormones, 3,5,3 ,5 -tetraiodothyronine
(T 4 ) and 3,5,3 -triiodothyronine (T3 ), and the inactive hormone,
3,3 ,5 -triiodothyronine (reverse T3 or rT 3 ). The rT 3
is the inner deiodination product of the T 4 . The structures
of the individual hormones are given in Figure 20-2 . The
T 4 molecule contains 65.3% iodine, and the T 3 molecule
contains 58.5% iodine. The T 3 is the active hormone in the
target cell. The T 4 functions as the transport form and as
the feedback regulator of the thyroid gland.
B . Hormonogenesis and Release
1 . Trapping of Iodide
The I
in the general circulation is taken up by the thyroid
follicular cells by a highly efficient trapping and concentrating
mechanism. It does this against a large concentration
gradient, which can be from 1:20- to 1:500-fold across
the thyroid cell membrane and is stimulated by TSH.
The trapping process is catalyzed by a trapping enzyme,
requires oxygen, and is an active transport or “ pump ”
mechanism catalyzed by a Na K -ATPase and dependent
on ATP. The transport process is mediated by a sodium
iodide symporter (NIS) protein located on the plasma
membrane ( Riesco-Eizaguirre and Santisteban, 2006 ). It
is the high efficiency of this trapping system that concentrates
virtually all of the body iodine in the thyroid gland.
It also accounts for the microgram nutrient requirement
for iodine. In addition, the thyroid follicular cells have a
high capability for compensatory hypertrophy when there
is a scarcity of iodine, hence the development of iodine
deficiency goiters. The efficiency of I trapping is also the
basis for the radioactive iodine uptake ( 131 I Uptake) test of
thyroid function, 131 I thyroid imaging, and 131 I thyroid therapy.
The trapping of I is stimulated by TSH and blocked
by the goitrogenic agents such as thiocyanate (SCN-), perchlorate
(CLO 4 -) and by large amounts of I . Figure 20-1
also shows the sites of these and other blocks in the thyroxine
biosynthetic pathway. Other compounds are trapped
by the thyroid gland, and the most widely clinically used
one is 99m Tc-pertechnetate, which is used for thyroid tissue
imaging.
2 . Synthesis of Thyroid Hormones
After trapping, there is an oxidation of I catalyzed by
a peroxidase and the product is a highly active form of
iodine, most likely a free radical, I * . This reaction is inhibited
by thyrotoxic agents such as the thiouracils or thioureas
and stimulated by TSH. Propylthiouracil is commonly
used in the treatment of hyperthyroidism. The I * almost
instantaneously binds to the phenyl groups of the tyrosine
moieties of thyroglobulin at the 3 or 5 position to form a
monoiodotyrosine (MIT) or a diiodotyrosine (DIT). This
iodination occurs while the tyrosines remain in polypeptide
linkage within the thyroglobulin molecule. Next, the
iodinated phenyl groups of the tyrosines are coupled by
the oxidative condensation of an iodinated phenyl group of
one DIT to another DIT to form T 4 or of an MIT group to
a DIT to form T 3 . These iodination reactions occur mainly
at the follicular cell membrane-colloid interface. These
iodination reactions are energy requiring and sensitive to
blocking by sulfa drugs, thioureas, and paraaminobenzoic
acid (PABA).
3 . Storage of Hormone
Thyroglobulin is the thyroidal glycoprotein of high molecular
weight (660,000 daltons) synthesized exclusively by