THYROID METABOLIC HORMONES

 Thyroid gland secretes two hormones T3 or triiodothyronine and T4 or

tetraiodothyronine or thyroxine
 Defect in thyroid gland causes the metabolic rate to fall about 40-50% below normal
and excess of thyroid hormone causes the metabolic to increase about 60-100%
above normal
 Secretion mainly controlled by TSH
 Thyroid gland is composed of many cells called follicle cells which are filled with
colloid. Colloid is lined with colloidal epithelial cells.
 This gland also has parafollicular cells which secrete the hormone calcitonin
 Iodine is very essential for the formation of thyroid hormones usually majority of the
iodine is excreted but around one fifth of it is absorbed by the thyroid gland from the
circulation
 IODINE TRANSPORT
 Iodine is transported from blood into thyroid gland with the help of a co transporter
Na. concentration of iodine in the gland is much higher than the blood.
 So through active transport iodine is transported into the gland
 The energy for active transport is provided by Na-K ATPase.
 This way iodine is trapped in the gland and this is known as iodine trapping.
 From the thyroid gland iodine is transported to the follicular cell with the help of
another transporter called pendrin where basically iodine is transported to the
follicular cell in exchange of chloride ion
 T3 AND T4 FORMATION
 There is protein called thyroglobulin which is synthesised in the endoplasmic
reticulum of thyroid gland and through golgi apparatus transported in to the
follicular cell
 This protein is where the hormones are stored. It contains many tyrosine molecules where
the iodine comes and attaches which leads to the formation of T3 and T4

 In this diagram the formation and storage of T3 AND T4 are shown

 Iodine enters into the thyroid gland as explained above. As it moves from the thyroid into
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the follicular cell there is a peroxidase enzyme which oxidizes I to I 2. This enzyme also
attaches the I2 to the tyrosine molecule on the thyroglobulin.
 After the attachment of I2 to the tyrosine molecule on the thyroglobulin molecule it either
forms monoiodothyronine(MIT) or diiodothyronine(DIT).
 In the next either MIT AND DIT combines to form triiodothyronine or T3 or DIT AND DIT
combines to form tetraiodothyronine or T4. Small amount reverse T3 is also formed but its
not functional in humans.
 T3 AND T4 remains attached to the thyroglobulin in the follicular cell until there is signal
that tell the hormones to be secreted in the blood.
 Once there is signal thyroid gland forms a pinocytic vesicle around the thyroglobulin which
has the hormone and releases proteases which cleaves the T3 and T4 from thyroglobulin and
releases it into the blood
 MIT and DIT are mostly not released in the blood as they are cleaved by deiodinase enzyme
where iodine is again released in to the cell for future use
 Usually thyroglobulin doesn’t leave the thyroid gland but some amount which combines
with an enzyme called megalin helps it to be transported into to the blood.
 Forgot to mention – the process of combining iodine to tyrosine is called organification.
 Most of the hormone that is formed is mainly T4 and very little about 7% is T3 but for
functioning T4 is converted into T3.
 As the thyroid hormones are always bound to the protein their speed of action is slow
 T4 has higher affinity to plasma proteins so they take around 6 days to be released and show
their actions where T3 has lesser affinity to plasma proteins so they can easily be released
and takes around 1 day
 If a T4 injection given takes about 6 days for the action to occur as the latent period is long
due their attachment with plasma proteins. It reaches it max activity level in the 10 or 12
days.
 PHYSIOLOGICAL FUNCTIONS OF THYROID HORMONE
 Thyroid hormones activate nuclear receptors.
 Thyroid hormone receptors located in the nucleus or near the DNA. Thyroid hormone
receptor is attached to another receptor called retinoid X receptor. And these two attach
together to hormone response element(HRE).
 This full complex translates many new proteins which bring about changes in the cell.
 Thyroid
hormones
also has
many non
 genomic effects like activate secondary messengers like cAMP and regulation of ion
channels.
 When thyroid hormone is given to an animal the no of mitochondria and their size increases
 One enzyme that is affected by this hormone is Na-K ATPase, which helps in the transport of
ions. These hormones also make the cells leaky to Na ions which causes excess of heat
production
 These hormones have a great effect on growth hormone. Hypothyroidism can cause
dwarfism and in case of hyperthyroidism growth of bones happen at an early stage which
causes the children to grow taller at a young age but also this causes the epiphyses of the
bone to close at an early age which stops the growth.
 Thyroid hormone also causes the growth and development of brain in fetal life.
 Increase all aspects of carbohydrates metabolism. Increase glucose uptake by cells, glycolysis
and gluconeogenesis.
 Increases fat mobilization. Doesn’t allow the fats to be stored in the cells. Causes high fat
content in plasma so for energy source fat can be used easily
 Increased thyroid hormones cause decrease in cholesterol, triglycerides and phospholipids
 One way to decrease cholesterol in plasma is to increase the receptors of LDL on liver so
they can be easily removed from there
 Increase in thyroid hormones can cause vitamin deficiency
 Increase also causes a decrease in the body weight
 It causes the rapid utilization of oxygen which increases the metabolic rate which causes the
vasodilation of blood vessels. Vasodilation of blood vessels in skin is also increased in order
to eliminate the heat from the body. This causes the blood flow to increase. The increase in
blood flow causes the cardiac output to increase.
 Increase heart rate and also heart strength. But excessive thyroid hormone causes the heart
muscles to become depressed due to excess of protein catabolism, so at times the patient
can die due to cardiac decompensation in case of hyperthyroidism.
 Arterial pressure remains same but pulse pressure increases
 Increases respiration rate and gastrointestinal motility
 Increases the excitory effects on CNS.
 Cause muscle tremor due to increased signals to the spinal cord
 Due to the exhausting effect of thyroid hormone on muscles it becomes difficult to sleep in
case of hyperthyroidism
 It increases the need of other hormones such as insulin and PTH
 In men lack of thyroid hormone causes lack of libido. In women it causes menorrhagia
(excessive bleeding during menstrual cycles) and polymenorrheae (frequent bleeding)
 Hypothyroidism in women causes oligomenorrhea (reduced bleeding)
 REGULATION OF THYROID HORMONE SECRETION
 Mainly controlled by TSH
 All the steps mentioned above in the cycle are affected directly by TSH
 TSH attaches to the receptor on thyroid gland activates adenylyl cyclase which converts ATP
to secondary messenger cAMP, which in turn causes many reactions.
 TSH is controlled by TRH produced in the hypothalamus. TRH attaches to the receptor in
pituitary gland and activates phospholipase C which causes the release of TSH.
 Cold temperatures in case of animals also increases TRH secretion
 There is hormone in hypothalamus called leptin which also affects the secretion of TRH
 Certain emotions also affect their secretion like anxiety and excitement reduces thyroid
hormones secretion
 REGULATION
 Has negative regulation
 An increase in thyroid hormones in the blood causes the TRH to be inhibited and which in
turn inhibits the TSH
 EXTRA POINTS
 Thiocyanate ions inhibit iodine trapping
 It acts as competitive inhibitor for iodine.
 It doesn’t do anything but just reduces the iodine conc. in thyroid gland so iodine does not
bind to tyrosine molecule in thyroglobulin
 Propylthiouracil blocks the formation of thyroid hormones. It blocks the enzyme
peroxidase(use told before)
 Both these of drugs stops the formation of T3 AND T4 so TSH keeps increasing ( due to
negative feedback) which causes the enlargement of thyroid gland
 DISEASES
 GRAVE’S DIASEASE
 Most common cause of hyperthyroidism
 Produces thyroid stimulating immunoglobulins (TSIs) which attach to the receptor of TSH
and stimulate the secretion of thyroid hormone uncontrollably.
 Increased hormones production suppresses the release of TSH.
 Thyroid adenoma – tumour in thyroid gland, another cause of hyperthyroidism
 People suffering from hyperthyroidism may also have exophthalmos that is protrusion of the
eyes this as well might be an autoimmune disorder.
 For majority of the treatments, it is advised to remove the thyroid gland
 HYPOTHYROIDISM
 Lack of thyroid hormone production
 Hashimoto’s disease – destroys one’s own thyroid gland
 One of the main cause thyroiditis
 Endemic goitres – was mainly caused in the era where there no iodized salts available
 So lack of iodine caused this goitre
 Since no iodine was available the hormones weren’t produced, excessive amount of TSH was
released which caused the thyroid glands to grow larger in size
 Idiopathic non toxic goitre – there is no iodine deficiency in this goitre, the reason for this is
still unknown maybe caused due to thyroiditis.
 This goitre blocks the pathway involved in thyroid cycle (mentioned above )
 Myxedema – in patient who’s thyroid gland is completely destroyed
 Bagginess under eyes, hight level of hyaluronic acid and chondroitin sulfate
 Hypothyroidism causes atherosclerosis
 Treatment - Oral ingestion of thyroid hormones can help to treat hypothyroidism
 Cretinism – extreme case of hypothyroidism in infants and children
 Cause defect in growth and mental retardation
 If its due to lack of iodine it might be called endemic cretinism
 A new born may seem normal without a thyroid gland in the mothers womb as the mothers
thyroid gland is supporting but after birth the child will experience growth issues and mental
retardation