THYROID

HORMONE
S ANSH JAIN
ROLL NO.23101038
Introduction to Thyroid
◦ The thyroid gland, a small butterfly-shaped organ located in the front of the neck, plays
a
crucial role in regulating metabolism, growth, and development

◦ . These hormones exert their effects

on virtually every cell in the body
and are essential for maintaining
overall health and well-being.
Thyroid hormones
◦The principal hormones synthesised and secreter thyroid gland
are;
◦T, (thyroxine)
◦I, (triiodothyronine).
◦RT, (reverse-triiodothyronine), secreted in small quantity
◦Calcitonin
◦Thyroid hormones also play a critical role in maintaining body
temperature,
heart rate, and the function of the nervous and reproductive
systems.
◦Disorders of the thyroid gland can lead to dysregulation of
hormone
◦T4, T3 and RT3 are secreted from
thyroid follicles calcitonin is
secreted from the parafollicular
cells (C of thyroid gland.
◦Normally, T3 is more active than T4,
though T4
is secreted in more quantity from thyroid
gland.
◦T4 is converted to T3 in the peripheral
blood and
tissue Therefore, T4 is mainly a
prohormone.
◦RT3 is physiologically inactive.
◦The raw materials required for thyroid
hormone
Key players in thyroid hormone
synthesis
◦ Iodine: An essential mineral required for thyroid hormone synthesis.

◦ Thyroglobulin: A large glycoprotein synthesized by thyroid follicular cells, serving as

a scaffold for thyroid hormone synthesis.

◦ Thyroid Peroxidase (TPO): An enzyme located on the apical surface of thyroid

follicular cells, responsible for iodine oxidation and coupling reactions.
lodine metabolism
◦• lodine is required for the formation of
thyroid
◦(150-200g/day) (sr 5-10 ug/dL)
◦About 80% is stored in Thyroid gland.
◦Ingredients which prevent the
utilization of lodine are called as
Goitrogens.
◦daily ingestion of 150 mg of
iodine in an adult maintains
normal thyroid function.
◦The thyroid gland actively
uptakes iodine from the
bloodstream
Steps of Thyroid Hormone synthesis
◦ Iodide Uptake: Iodide ions are actively transported into thyroid follicular cells from
the bloodstream via the sodium-iodide symporter (NIS).
◦ Iodide Oxidation: Within thyroid follicular cells, iodide ions are oxidized to iodine (I2)
by
Thyroid Peroxidase (TPO).
◦ Iodination of Thyroglobulin: Iodine is attached to tyrosine residues within
thyroglobulin,
forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).
◦ Coupling Reactions: MIT and DIT residues combine to form thyroxine (T4) and
triiodothyronine (T3), the active thyroid hormones.
◦ Storage: T4 and T3 are stored within the colloid-filled follicles of the thyroid gland,
bound to thyroglobulin.
IODINE TRAPPING

◦Uptake of iodide by thyroid

gland.
◦By lodine pump or Na/I-
symporter.
◦Thyroid stimulating hormone -
controls iodide uptake.
◦Anti-thyroid agents -
◦Thiocynate & Perchlorate
inhibit
lodide transport.
SYNTHESIS & SECRETION OF
THYROGLOBULIN
◦Thyroglobulin - large Glycoprotein synthesized
in rough endoplasmic reticulum of thyroid
epithelial cells & then released into lumen.
◦1 molecule of Thyroglobulin contains - 140
thyrosine residue which is a substrate for
iodine for thyroid hormone synthesis.
OXIDATION OF
IODIDES.
◦Once inside gland iodide is taken into
lumen by
transporter - Pendrin.
◦Then iodide is oxidised to lodine by
enzyme. Peroxidase.
ORGANIFICATION OF
THYROGLOBULINS.
◦Iodination of tyrosine residue in
thyroglobulin
molecule.
◦Tyrosine is 1s iodinated at position 3
to form Mono-iodotyrosine
(MIT) & then at position 5 to form Di-
iodotyrosine (DIT)
COUPLING REACTION.
◦One molecule of MIT & DIT coupled to
formTriiodothyronine(Т3)

◦ 2 molecules of DITcoupled to formThyroxine (T4)

STORAGE.
◦Once Thyroglobulin is iodinated is stored in lumen.
◦Stored thyroid hormones can meet body
requirements for1-3
months.
SECRETION
◦Endocytosis - colloid containing
iodinated
Thyroglobulin is secreted by
Endocytosis.
◦Colloid enters the cytoplasm as
colloid droplets.
◦Proteolysis - colloid droplets fuses
lysosome vesicles containing
proteolytic enzymes & releases T3,
T4, MIT & DIT.
TRANSPORT
◦Bound form - most of T3 & T4 are
bound to
specific proteins.
◦Thyroxine binding Globulins - bind
70% of T3 & T4.
◦Free form - 0.5% of T3 & 0.05% of
T4.
METABOLIS
M
◦Deiodination - about 40% T4 deiodinated into T3 by enzyme 5'-
deiodinase.
◦Decarboxylation - very few decarboxylated to form
tetraiodothyroacetic acid &
tri-iodothyroacetic acid.
◦Conjugation - 15% T3 & T4 are conjugated in liver to form
glucoronides &
sulphates.
Regulation of thyroid hormone synthesis
◦ Thyroid-stimulating hormone (TSH), produced by the pituitary gland, stimulates
thyroid
hormone synthesis and release.
◦ TSH secretion is regulated by thyrotropin-releasing hormone (TRH) from the
hypothalamus, forming the hypothalamus-pituitary-thyroid (HPT) axis.
◦ Feedback mechanisms involving thyroid hormones and TSH maintain thyroid hormone
levels within a narrow range.
◦ Thyroid hormone synthesis is a complex process essential for maintaining metabolic
homeostasis and overall health.
◦ Understanding the key steps and regulatory mechanisms involved in thyroid hormone
synthesis provides insights into thyroid disorders and potential therapeutic
interventions.
Functional overview
◦ Metabolic regulation

◦ Temperature regulation

◦ Cardiovascular function

◦ Neurological development

◦ Reproductive health
 Metabolic Regulation
◦ - Basal Metabolic Rate (BMR): Thyroid hormones influence the rate at which cells utilize
oxygen
and produce energy, thereby regulating BMR.-
◦ Lipid Metabolism: T3 and T4 stimulate lipolysis, the breakdown of stored fats, leading to
increased fatty acid oxidation and energy production.-
◦ Thermogenesis: Thyroid hormones increase heat production through mitochondrial uncoupling,
where energy is dissipated as heat instead of being used for ATP synthesis.-
◦ Protein Metabolism: T3 and T4 promote protein synthesis and degradation, maintaining protein
turnover and tissue integrity.-
◦ Insulin Sensitivity: Thyroid hormones influence insulin sensitivity in peripheral tissues,
affecting
glucose uptake and utilization.
Temperature regulation
◦ Thyroid hormones play a crucial role in maintaining core body temperature within a
narrow range.
◦ T3 and T4 influence thermogenesis, the production of heat by the body, through
their
effects on metabolism.-
◦ Increased metabolic rate induced by thyroid hormones results in heightened
heat production as a byproduct of energy generation.-
◦ Thyroid hormones enhance blood flow to the skin, facilitating heat loss
through
radiation and convection
◦ Hypothyroidism, characterized by reduced thyroid hormone levels, can lead to
cold
intolerance and impaired thermoregulation.-
Cardiovascular Function
◦ - Thyroid hormones exert profound effects on cardiovascular function, including heart
rate, contractility, and vascular tone.-
◦ T3 and T4 increase heart rate by enhancing the responsiveness of cardiac pacemaker
cells
to sympathetic stimulation.-
◦ Thyroid hormones augment myocardial contractility, leading to increased stroke volume
and cardiac output.-
◦ T3 and T4 influence vascular tone by modulating the expression of vasodilator and
vasoconstrictor molecules in blood vessels.-
◦ Thyroid hormone imbalance can lead to cardiovascular abnormalities, such as
tachycardia, palpitations, and hypertension in hyperthyroidism, and bradycardia
and reduced cardiac output in hypothyroidism.-
◦ Proper thyroid hormone levels are essential for maintaining cardiovascular
homeostasis
Neurological Development
◦ - Thyroid hormones play a critical role in neurological development, particularly during
fetal development and early childhood.-
◦ T3 and T4 are essential for neuronal migration, the process by which neurons migrate
to
their proper locations in the developing brain.-
◦ T3 and T4 are necessary for myelination, the process by which nerve fibers are coated
with myelin, a fatty substance that enhances signal transmission.-
◦ Thyroid hormone deficiency during critical periods of brain development can lead to
cognitive impairment, intellectual disability, and neurological deficits.-
◦ Proper thyroid hormone levels are crucial for optimal neurological function throughout
life, including learning, memory, and motor coordination.
Reproductive health
◦ T3 and T4 influence the synthesis and secretion of gonadotropin-releasing hormone
(GnRH) from the hypothalamus.-
◦ Thyroid hormones modulate the production and secretion of luteinizing hormone
(LH)
and follicle-stimulating hormone (FSH) from the pituitary gland.-
◦ T3 and T4 regulate the menstrual cycle in females by influencing ovarian follicle
development, ovulation, and corpus luteum function.-
◦ Thyroid hormones are essential for spermatogenesis, the process of sperm production,
in males.
◦ - Thyroid hormone imbalances can disrupt reproductive function, leading to
menstrual irregularities, infertility, and sexual dysfunction.-
◦ Proper thyroid hormone levels are necessary for maintaining reproductive health and
fertility in both men and women.