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Physiology Lecture no. 5
Date 13/2/2011
In this lecture we will talk about Thyroid Gland, TSH, and TRH.
Thyrotropin-Releasing Hormone (TRH) which is a tripeptide amide that is synthesized in the
hypothalamus and stored in the median eminence and produced from the anterior pituitary
gland. It directly affects the output of the TSH (also known thyrotropin )
TSH :
Thyroid Gland stimulated by thyroid stimulating hormone (TSH) which is a glycoprotein ,
secreted from the anterior pituitary gland.
It has specific effects on the thyroid gland , as follows :
1-stimulates the growth of thyroid gland
2-increase the synthesis and secretion of thyroid hormone
TSH is composed of 2 subunits:
1- α (non specific), doesn’t function and found in other hormones
1-LH (luteinizing hormone)
2-FSH (follicle stimulating hormone)
3-HCG (Human Chorionic Gonadotropin)
2- β (specific), Biological active part BUT to function it should be combined with the α subunit.
The release of TSH is inhibited by Dopamine , Somatostatin and cortisole and growth hormon
(because both stimulate the release of somatostatin).
Most of the effects of TSH on the thyroid cells result from the activation of the “second
messenger “ cAMP, through which TSH stimulate the gland growth and will increase the
synthesis and secretion of thyroid hormone.
Also TSH activates another two second messengers 1-DAG (diacylglycerol)
2-IP3 (Inositol triphosphate)
BUT these two messengers have nothing to do with the growth, secretion and synthesis of
thyroid hormones.Most probably they have something to do with the phospholipids
metabolism in thyroid cells.
The Thyroid Gland produces three hormones: 1- mainly T4( thyroxine)
2- Tribute amount of T3 (triiodothyronine)
3- Reverse T3 (reverse triiodothyronine)
The anatomy of the thyroid gland :
The Thyroid gland is composed of two lobes (right lobe and left lobe) joined by part called
isthmus (it is about 25 grams)moreover it is rich with blood supply(100ml/min) , it is located in
front of the trachea..
Embryological development of the thyroid gland :
BY 12 weeks of human gestation the gland is capable of synthesizing and secreting thyroid
hormones under the stimulation of the fetal hypothalamus and pituitary gland. This entire axis is
required for subsequence normal intrauterine development of the central nervous system and
the skeleton. To simplify thyroid hormones are essential for normal development of the
central nervous system and the skeleton of the fetus.
REMEMBER Thyroid gland is very important even during fetal life.
Physiologic anatomy of the thyroid gland:
If we take a section through thyroid gland we will see that it is composed of large number of
closed follicles , Each follicle is full of colloid fluid which contains proteins, hormones and
enzymes and lined with cuboidal epithelial cells that synthesize and release the thyroid
hormone.
In between these follicles there are some other cells called “parafollicular cells” OR “ C cells”
these cells release unrelated hormone called “calcitonin” which reduces the calcium level in the
blood.
.Chemistry of hormones:
1-mainly proteins (1 a.a chatacolamese) (2 a.a thyroid hormone)
2-Amino acid derivatives
3-Steroids (synthesized in adrenal cortex) eg. Male and female hormones
Chemistry of Thyroid Hormones: Thyroid hormones are derivatives of the amino acid
tyrosine -found in the thyroglobulin which is a large glycoprotein molecule secreted into
thefollicles of the gland - .
putting in mind that the tyrosine derivatives are the major substrates that combine with iodine
The iodination of tyrosine results in iodotyrosine , and its named according to the
number of the iodine molecule that binds the tyrosine EX: mono-iodotyrosine ,diiodotyrosine, … etc
Formation of the thyroid hormones :
T4,T3 and rT3 all are products of the coupling of two iodinated tyrosine derivatives
mono-iodotyrosine + di-iodotyrosine  tri-iodotyrosine (triiodothyronine ) (T3)
di-iodotyrosine + di-iodotyrosine  tetra-iodotyrosine (thyroxine) (T4)
. Thyroid gland produces mainly T4. T4 is either very week or inactive so it is deiodinated to
form additional T3 or totally inactive reverse T3 (rT3).
Deiodination of thyroxin :
High Metabolic rate  T4 is converted into T3
Low metabolic rate
 T4 is converted into rT3
What is the difference between T3 and rT3?
The only difference is the iodine location on tyrosine
(T3 , rT3 and T4) are called Iodothyronine
Thyroid gland produces and stores both Iodothyronenes and Iodotyrisines
Thyroid gland differs from other glands by :
1-the only gland that stores hormone
2-incorporates inorganic sb. With organic sb.
EX. ( Iodine and tyrosine)
** REMEMBER: each tyrosine maximally can carry 2 Iodine.
*When there is too much thyroxine and cannot be converted into T3 and rT3 , it will be
converted into “tetra iodo acitic acid” (tetrac).
Synthesis and secretion of thyroid hormones
1-Iodine binds with tyrosine this is called iodination
Source of iodine: 1-Mainly comes from plasma (enter with sodium) 2-comes from deiodinated
thyroid hormones
2-Thyroid cells synthesis protein called thyroglobulin
Thyroglobulin is composed of a sequence of tyrosine amino acids (composed at least 70 a.a or
70 thyrosines) as mentioned earlier the tyrosine derivatives are the major substrates that
combine with iodine.BUT not all the 70 tyrosine derivatives can carry iodine, only about 4-8 can
carry iodine.
*when 1mono-iodotyrosine binds with 1 di-iodotyrosine on the structure of the thyroglobulin
this is called coupling.
*also when 1 di-iodotyrosine binds with 1 di-iodotyrosine on the structure of the thyroglobulin
this is called coupling.
-Iodination and coupling don’t occur on free tyrosine.
*Thyroglubulin released into colloid carries 1-MIT
2-DIT 3-T3
4-rT3
5- T4
Storage of thyroid hormone is sufficient for 2-3 months. the content of iodine within the thyroid
gland is 100 times greater than the amount needed daily.
In the colloid thyroglubulin carries all of these (MIT, DIT, T3, T4, rT3) in need, is taking back by
pinocytosis process inside the epithelial cells ,the thyroglobulin under the effect of enzymes
releases T4, T3 and rT3 . MIT and DIT and thyrosines are reutilized again.
Thyroid hormone turnover (see table 53-1)
The doctor talked about 1-Daily production (the largest production for T4) (T3 and rT3 have the
same amount)
2-From thyroid
3-from T4
4-Half life (the inactive form has longer half life)
*99.5% of T3 bound to thyroglubulin so the free T3 is only .5%
The free is the active and functioning part. So very little of thyroid hormones are free
Because it is very efficient hormones it is produced in very minute quantity.
*white T4 just .02% is free so there is 99.98% bound .
As we said the free is the active and functioning part so we conclude that
T3 is more active than T4.
Thyroid hormone binding proteins (see the table 5.3.3)
The doctor talked about the three proteins and the actual binding of T4 and T3 with
these proteins.
Proteins
actual binding T4 %
actual binding T3 %
TGB
75
75
Albumin
10
25
TBPA
15
00
What is the advantage of binding the thyroid hormones with the proteins?
1-preventing them from filtration through the kidneys
2-to prolong their half life
NOW we will talk about the Figure 40-6 (page 15)
T3 and T4 are small molecules they penetrate cell membrane, nuclear membrane, and
bind with the receptors affecting DNA then produce messenger RNA
That will increase1- Na+,K+-ATPase
2-respiratory enzymes
3-other enzymes and proteins
Also O2 consumption will increase that will
1- increase cardiac output
2- increase ventilation
3-more substrate is needed so 1- increase food intake
2-increase mobilization
Also the Metabolic rate will increase
That will 1-increase CO2
2-increase urea
3-decrease muscle mass
4-decrease adipose tissue
5-increase thermo genesis
The doctor mentioned that table 13-6 is is a revision .
Factors Affecting Thyroid Hormone Secretion
Stimulatory factors
1-Thyroid-stimulating immunoglobulins
2-TSH
3-Increased TBG levels
Inhibitory Factors
1-Iodine deficiency
2-Deiodinase deficiency
3-excessive iodine intake
4-perchlorate; thiocyanate
5-Propylthiouracil
6-Decreased TBG levels
And Finally the doctor read the page 19 in the slides but without any explanations
Done by :George Deeb
GOOD LUCK