Download The role of thyroid hormones in the regulation of metabolism

The role of thyroid hormones in
the regulation of metabolism.
THYROID GLAND
• Thyroid gland
synthesizes two
kinds of hormones:
iodine containing
hormones and
calcitonin.
Hormones of two types:


1. Iodine containing
: thyroxin
(tetraiodthyronin)
and triiodthyronin –
derivatives of
tyrosine;
2. Calcitonin peptide
Synthesis of
iodine
containing
hormones is
regulated by
thyrotropic
hormone, which
in turn is
stimulated by
thyroliberin
Thyrotropic hormone (TTH).
Chemical structure: glicoprotein.
This hormone is necessary for the normal functions of thyroid
glands.
Thyrotropic
hormone
promotes:
•accumulation of iodine in
thyroid;
•including of iodine into the
tyrosine;
•synthesis of thyroxine and
triiodothyronine.
In difference to hormones of
protein and peptide nature, receptors
for steroid hormones are located
within the cells - in the cytoplasm.
From cytoplasm the hormonereceptor complexes is translocated
into the nucleus where they interact
with DNA of nuclear chromatin
causing the activation of genes for
respective enzyme proteins.
So, if hormones of the first group
cause the activation of existing
enzyme molecules, the acting on the
target cells of steroids and thyroid
hormones results in the biosynthesis
of new enzyme molecules.
CHEMISTRY STRUCTURE OF THYROID HORMONES:
Thyroxine and triiodthyronine
are iodinated derivatives of amino
acid tyrosine.
Formation and Secretion of Thyroglobulin by the Thyroid Cells.
The thyroid cells are typical protein-secreting glandular cells. The
endoplasmic reticulum and Golgi apparatus synthesize and secrete
into the follicles a large glycoprotein molecule called thyroglobulin,
with a molecular weight of about 335,000.
Each molecule of thyroglobulin contains about 70 tyrosine amino
acids, and they are the major substrates that combine with iodine
to form the thyroid hormones.
Transport of thyroxine and triiodothyronine to tissues:
They combine mainly with
Thyroxin-binding globulin <90%
Thyroxin-binding pre-albumin
Thyroxin-binding albumin.
MEHANISM OF ACTION OF
THYROID HORMONES:
The thyroid hormone
receptors are either attached
to the DNA genetic strands
or located in proximity to
them.
The thyroid hormone
receptor usually forms a
heterodimer with retinoid X
receptor (RXR) at specific
thyroid hormone response
elements on the DNA.
MEHANISM OF ACTION OF
THYROID HORMONES:
On binding with thyroid
hormone, the receptors become
activated and initiate the
transcription process.
Then large numbers of different
types of messenger RNA are
formed, followed within another
few minutes or hours by RNA
translation on the cytoplasmic
ribosomes to form hundreds of
new intracellular proteins
Functions of iodine containing
hormones
Necessary for
normal growth,
differentiation,
sex and mental
development
Regulate the
speed of
metabolism
Effect of thyroxine and triiodthyronine
on the protein metabolism:
•In physiological concentration stimulate
the synthesis of proteins and nucleic acids.
• In the increased concentration activate
the protein decomposition.
Effect on lipid metabolism
Activate the exit of lipids from depot,
its decomposition and oxidation
Effect on carbohydrate metabolism
Accelerate the absorption of
carbohydrates in the intestine
Activate the decomposition of glycogen.
Effect on energetic metabolism
In excess thyroxin uncouples
respiration and phosphorilation,
decreases the ATP formation and
increases the heat formation
Hypofunction of gland (occurs in the deficit of
iodine in water, soil, air)
•Decrease of metabolism
•Decrease of body temperature
Hypofunction in adults –
mixedema
•Edema of mucosa
mixedema
Hypofunction of gland
(occurs in the deficit of
iodine in water, soil, air)
•Decrease of metabolism
•Decrease of body temperature
Hypofunction in childhood cretinism
•Growth inhibition
•Unproportional body
development
•Disorders of mental
development
cretinism
Endemic goiter
(occurs in the
deficit of iodine in
water, soil and air)
Connective tissue is
enlarged in gland and
it is increased in size
markedly
Hyperfunction of gland –
diffuse toxic goiter
(thyrotoxicosis, Graves
disease)
•Goiter – hyperplasia of gland
•Hypermetabolism
•Increase of body
temperature
•Sweating, muscle weakness
•Weight loss with good
appetite
•Tremor, emotional lability,
insomnia
•Exophtalm