The Endocrine System
337
SECTION C
The Thyroid Gland
Synthesis of Thyroid Hormones
Thyroid hormones exert widespread and diverse effects
throughout the body. The actions of TH are so important—
and the consequences of imbalances in TH concentrations so
severe—that it is worth examining thyroid gland function in
additional detail.
The thyroid gland produces two
iodine
-containing mol-
ecules of physiological importance,
thyroxine
(called T
4
because it contains four iodines) and
triiodothyronine
(T
3
,
three iodines; review Figure 11–2). T
4
generally is converted
into T
3
by enzymes known as deiodinases in target cells. We
will therefore consider T
3
to be the major thyroid hormone,
even though T
4
is the major secretory product of the thyroid
and total T
4
concentrations are higher in the blood.
The thyroid gland is a bilobed structure that sits within
the neck straddling the trachea (
Figure 11–21a
). It fi
rst
becomes functional early in fetal life. By adulthood, the thy-
roid gland weighs about 25 grams.
Within the thyroid gland are numerous
follicles,
each
composed of an enclosed sphere of highly specialized cells sur-
rounding a core containing a protein-rich material called the
colloid
(
Figure 11–21b
). The follicular cells participate in
almost all phases of thyroid hormone synthesis and secretion.
Synthesis begins when circulating iodide is cotransported with
sodium ions across the follicular cell plasma membrane (step 1
in
Figure 11–22
). Once inside the follicular cell, the bulky
iodide ion cannot diffuse back into the interstitial fl
uid; this is
known as
iodide trapping.
The sodium is eventually pumped
back out of the cell by Na
+
/K
+
-ATPases.
The trapped, negatively charged iodide ions diffuse
down their electrical and concentration gradients to the
lumenal border of the follicular cells (step 2). The colloid
of the follicles contains large amounts of a protein called
thyroglobulin.
The iodide that diffuses to the colloid is
rapidly oxidized at the lumenal surface of the follicular cells
to iodine free radicals; these are then attached to the phenolic
rings of tyrosine molecules within the amino acid structure
of thyroglobulin (step 3). Thyroglobulin itself is synthesized
by the follicular cells and secreted by exocytosis into the folli-
cle lumen. The enzyme responsible for oxidizing iodides and
attaching them to tyrosines on thyroglobulin in the colloid is
called
thyroid peroxidase,
and it, too, is synthesized by fol-
licular cells. Iodines may be added to either of two positions
on a given tyrosine within thyroglobulin. A tyrosine with one
iodine attached is called
monoiodotyrosine (MIT);
if two
iodines are attached, the product is
diiodotyrosine (DIT).
The precise mechanism of what happens next is still some-
what unclear. The phenolic ring of a molecule of MIT or DIT
is removed from the remainder of its tyrosine and coupled to
another DIT on the thyroglobulin molecule (step 4). This
reaction may also be mediated by thyroid peroxidase. If two
DIT molecules are coupled, the result is thyroxine (T
4
). If
one MIT and one DIT are coupled, the result is T
3
.
Finally, when thyroid hormone is needed in the blood,
extensions of the colloid-facing membranes of follicular cells
engulf portions of the colloid (with its iodinated thyro-
globulin) by endocytosis (step 5). The thyroglobulin, with
its coupled MITs and DITs, is brought into contact with
lysosomes in the cell interior (step 6). Proteolysis of thyro-
globulin releases T
3
and T
4
, which then diffuse out of the
follicular cell into the interstitial fl uid and from there to the
blood (step 7).
Control of Thyroid Function
Essentially all of the actions of the follicular cells are stim-
ulated by TSH, which, as we have seen, is stimulated by
TRH. The basic control mechanism of TSH production is
the negative feedback action of TH on the anterior pituitary
Artery
Larynx
Thyroid gland
Common
carotid artery
Trachea
(a)
Thyroid
follicle
(contains
colloid)
Follicular
cells
Section of one follicle
(b)
Figure 11–21
Location of the bilobed thyroid gland (a), and a cross section
through several adjoining follicles fi lled with colloid (b).
previous page 365 Vander's Human Physiology The Mechanisms of Body Function read online next page 367 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off