Thyroid is an endocrine gland situated at the root of the neck on either side of the trachea. It has two lobes, which are connected in the middle by an isthmu. It weighs about 20 to 40 g in adults. Thyroid is larger in females than in males. The structure and the function of the thyroid gland change in different stages of the sexual cycle in females. Its function increases slightly during pregnancy and lactation and decreases during menopause.
HISTOLOGY OF THYROID GLAND
Thyroid gland is composed
of large number of closed follicles. These follicles are lined
with cuboidal epithelial cells, which are called the follicular
cells. Follicular cavity is filled with a colloidal
substance known as thyroglobulin, which is secreted by the
follicular cells. Follicular cells also secrete tetraiodothyronine (T4 or thyroxine)
and tri-iodothyronine (T3). In between the follicles, the parafollicular cells are
presen.
These cells secrete
calcitonin.
HORMONES OF THYROID GLAND
Thyroid gland secretes
three hormones:
1. Tetraiodothyronine or T4 (thyroxine)
2. Tri-iodothyronine or T3
3. Calcitonin.
T4 is otherwise known as thyroxine and it
forms about 90% of the total secretion, whereas T3 is only
9%
to 10%.
Chemistry
Both T4 and T3 are
iodine-containing derivatives of amino acid tyrosine.
Potency and Duration
of Action
The potency of T3 is four
times more than that of T4. T4 acts for longer period than T3. Duration of T4 action is four
times more than T3 action. This is because of the difference
in the affinity of these hormones to plasma proteins. T3 has less affinity for plasma proteins and combines loosely with them, so that it is released quickly. T4 has more affinity and strongly binds with plasma proteins,
so that it is released slowly. Therefore, T3 acts on the
target cells immediately and T4 acts slowly.
Half-life
Thyroid hormones have long
half-life. T4 has a long halflife of 7 days. Half-life of T3 is
varying between 10 and 24 hours.
Rate of Secretion
Thyroxine = 80 to 90 μg/day
Tri-iodothyronine
= 4 to 5 μg/day
Reverse T3 = 1 to 2
μg/day.
Plasma Level
Total T3 = 0.12
μg/dL
Total T4 = 8
μg/dL.
Metabolism of Thyroid
Hormones
Degradation of thyroid
hormones occurs in muscles,
liver and kidney
SYNTHESIS OF THYROID HORMONES
Synthesis
of thyroid hormones takes place in thyroglobulin, present in follicular
cavity. Iodine and tyrosine are essential for the formation of thyroid
hormones. Iodine is consumed through diet. It is converted into iodide and
absorbed from GI tract. Tyrosine is also consumed through diet and is absorbed
from the GI tract. For the synthesis of normal quantities of thyroid hormones,
approximately 1 mg of iodine is required
per week
or about 50 mg per year. To prevent iodine deficiency, common table salt is iodized
with one part of sodium iodide to every 100,000 parts of sodium chloride.
STAGES OF SYNTHESIS
OF THYROID HORMONES
Synthesis
of thyroid hormones occurs in five stages:
1. Thyroglobulin synthesis
2. Iodide trapping
3. Oxidation of iodide
4. Transport of iodine
into follicular cavity
5.
Iodination of tyrosine
6. Coupling reactions.
1. Thyroglobulin
Synthesis
Endoplasmic reticulum and
Golgi apparatus in the follicular cells of thyroid gland
synthesize and secrete
thyroglobulin
continuously. Thyroglobulin molecule is a large glycoprotein containing 140
molecules of amino acid tyrosine. After synthesis, thyroglobulin is stored in the
follicle.
2. Iodide Trapping
Iodide is actively transported
from blood into follicular cell, against electrochemical gradient. This process
is called iodide trapping. Iodide is transported into the follicular cell along
with sodium by sodium-iodide symport pump, which is also called iodide pump. Normally,
iodide is 30 times more concentrated in the thyroid gland than in the blood. However,
during hyperactivity of the thyroid gland, the concentration of iodide
increases 200 times more.
3. Oxidation of
Iodide
Iodide
must be oxidized to elementary iodine, because only iodine is capable of
combining with tyrosine to form thyroid
hormones. The oxidation of iodide into iodine occurs
inside the follicular cells in the presence of thyroid
peroxidase. Absence or inactivity of this enzyme stops the synthesis of
thyroid hormones.
4. Transport of
Iodine into Follicular Cavity
From the follicular cells,
iodine is transported into the follicular cavity by an iodide-chloride
pump called
pendrin.
5. Iodination of
Tyrosine
Combination
of iodine with tyrosine is known as iodination. It takes place in
thyroglobulin. First, iodine is
transported from follicular
cells into the follicular cavity, where it binds with thyroglobulin. This
process is called organification of
thyroglobulin. Then, iodine (I) combines with tyrosine, which is already
present in thyroglobulin. Iodination process is accelerated by the enzyme iodinase, which is secreted by follicular cells. Iodination
of tyrosine occurs in several stages.
Tyrosine
is iodized first into monoiodotyrosine (MIT) and later into di-iodotyrosine
(DIT). MIT and DIT are called the iodotyrosine residues.
6. Coupling
Reactions
Iodotyrosine residues get
coupled with one another. The coupling occurs in different
configurations, to give rise to different thyroid hormones.
Coupling reactions are:
i. One
molecule of DIT and one molecule of MIT combine to form tri-iodothyronine
(T3)
ii. Sometimes
one molecule of MIT and one molecule of DIT combine to produce another form of T3 called reverse T3 or rT3. Reverse
T3 is only 1% of thyroid output
iii. Two molecules of DIT
combine to form tetraiodothyronine (T4), which is thyroxine.
Tyrosine + I =
Monoiodotyrosine (MIT)
MIT + I =
Di-iodotyrosine (DIT)
DIT + MIT =
Tri-iodothyronine (T3)
MIT + DIT = Reverse T3
DIT + DIT = Tetraiodothyronine or
Thyroxine (T4)
STORAGE OF THYROID HORMONES
After synthesis, the
thyroid hormones remain in the form of vesicles within thyroglobulin and are
stored for
long
period. Each thyroglobulin molecule contains 5 or 6
molecules of thyroxine. There is also an average of 1 tri-iodothyronine molecule for every 10 molecules of thyroxine.
In combination with
thyroglobulin, the thyroid hormones can be stored for several
months. Thyroid
gland is unique in this,
as it is the only endocrine gland that can store its hormones for a long period
of about 4 months. So, when the synthesis of thyroid hormone stops, the signs and symptoms of deficiency do not appear
for about 4 months.
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