Thyroid Hormones Females


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Thyroid Hormones Females

  1. 1. THYROID HORMONES <ul><li>Dr. Umrana Mirza </li></ul><ul><li>Ref: Harper 25 th edition </li></ul><ul><li>Objectives: </li></ul><ul><li>Name the different tyrosine derived thyroid hormones and list the steps of their synthesis explaining the role of iodine </li></ul><ul><li>Describe the mechanism of storage,secretion,transport,degradation and excretion of tyrosine derived thyroid hormones. </li></ul><ul><li>List their metabolic effects. </li></ul>
  2. 2. <ul><li>Thyroid gland is located on either sides of the trachea just below </li></ul><ul><li>the larynx. </li></ul><ul><li>The tyrosine derived hormones secreted by thyroid gland are </li></ul><ul><li>1. Tri-iodothyronine(T 3 ) and </li></ul><ul><li>2. Tetra-iodothyronine or thyroxine ( T 4 ) </li></ul><ul><li>These hormones are necessary for the proper functioning of </li></ul><ul><li>almost all the systems and biological processes. </li></ul><ul><li>  </li></ul><ul><li>Synthesis of thyroid hormone requires </li></ul><ul><li>Iodine: is a trace element, requirement is 150 to 200µgm/ day. </li></ul><ul><li>Sources-drinking water, fish, cereals, vegetables and iodinated salt. </li></ul><ul><li>  Thyroglobulin: is a complex glycosylated protein ( 500 a.a), </li></ul><ul><li>synthesized by thyroid follicular cells. It has 115 tyrosine residues. </li></ul><ul><li>Amino acid-Tyrosine in thyroglobulin </li></ul>
  3. 3. Synthesis <ul><li>First step: Uptake and concentration of iodine by thyroid gland by an </li></ul><ul><li>Active process linked to Na+/ K+ ATP ase pump. </li></ul><ul><li>This step is stimulated by TSH and is inhibited by high concentration of iodine in </li></ul><ul><li>thyroid gland.  </li></ul><ul><li>Second step: iodine is than oxidized to active iodine . </li></ul><ul><li>Thyroid gland is the only organ which can perform this function. </li></ul><ul><li>This step is stimulated by TSH. Require Thyroperoxidase as enzyme and NADPH as </li></ul><ul><li>coenzyme. </li></ul><ul><li>Thyro peroxidase </li></ul><ul><li>Iodine- Active iodine+ </li></ul><ul><li>H2o2 </li></ul><ul><li>O2 </li></ul><ul><li> NADPH + H+ </li></ul><ul><li>  . </li></ul>
  4. 4. Third step: iodination of tyrosine. iodination of tyrosine takes place in the intact thyroglobulin molecule in the follicular space. Third position of aromatic ring is iodinated first to form MIT, Than the 5 th position to form DIT. Fourth step: Coupling of iodotyrosyls. DIT + DIT  T 4 DIT + MIT  T 3  Under normal conditions 99% of the hormone produced by thyroid gland is T 4 3,5,3’,5’ Tetraiodothyronine 3,5,3’ Tri-iodothyronine
  5. 5. Step-1 Uptake and concentration of iodine Step-2 Activation of iodine Step-3 Iodination of tyrosine Step-4 Coupling of iodotyrosyls Thyroid follicular cell Follicular space
  6. 6. <ul><li>Storage and secretion: </li></ul><ul><li>Synthesized thyroid hormone is stored as colloid in thyroid acini. </li></ul><ul><li>When stimulated by TSH the thyroglobulin is taken from the acinar colloid back into the cell by pinocytosis. </li></ul><ul><li>The hormone is than released by hydrolysis by specific proteases in lysosomes. </li></ul><ul><li>T4 is than released into the blood stream. </li></ul><ul><li>T3 is produced from T4 by deiodination at 5‘position in the peripheral tissues. </li></ul><ul><li>The MIT and DIT that are not utilized are deiodinated by deiodinase and the released iodine is reutilized. </li></ul>Thyroid cell Follicular space Blood
  7. 7. <ul><li>Transport </li></ul><ul><li>Thyroid hormone is lipophilic, therefore it is transported bound to proteins such as </li></ul><ul><li>thyroxine binding globulin(TBG), </li></ul><ul><li>thyroid binding pre-albumin(TBPA) and </li></ul><ul><li>albumin . </li></ul><ul><li>  1/2 to 2/3 rd of T4 and T3 bind with TBG & TBPA. </li></ul><ul><li>Bound form is biologically inactive. Free fraction is only 0.03%, which is biologically active. </li></ul><ul><li>T4 concentration is 70 times greater than T3 concentration in blood, but T3 is biologically more active. </li></ul><ul><li>Regulation </li></ul><ul><li>Free form of T3 and T4 inhibits the secretion </li></ul><ul><li>of TSH by negative feedback mechanism. </li></ul><ul><li> </li></ul>
  8. 8. <ul><li>Degradation and Excretion </li></ul><ul><li>Thyroid hormones are degraded in peripheral tissues by total deiodination </li></ul><ul><li>and inactivation. </li></ul><ul><li>  </li></ul><ul><li>First it is deiodinated and decarboxylated, followed by glucuronidation and </li></ul><ul><li>sulfation in the liver and made hydrophilic and therefore excreted in bile  </li></ul><ul><li>reabsorbed from the gut  reaches kidney and is excreted as glucuronide </li></ul><ul><li>Conjugate in urine. </li></ul><ul><li>  </li></ul><ul><li>Mechanism of Action </li></ul><ul><li>Group-I hormone </li></ul><ul><li>T3 and T4 bind to specific nuclear receptors. </li></ul><ul><li>T3 has more affinity to bind with nuclear receptors and hence biologically </li></ul><ul><li>more active. </li></ul><ul><li>Transported to the nucleus and binds with thyroid responsive element in the </li></ul><ul><li>DNA  increases rate of transcription  produces biochemical effect. </li></ul>
  9. 9. <ul><li>Biochemical Functions(metabolic effects) </li></ul><ul><li>1. Thyroid hormone stimulates the metabolic activity and increases the oxygen consumption in most of the tissues of the body. </li></ul><ul><li>2. Promote protein synthesis by acting at the transcriptional level. </li></ul><ul><li>3. Promotes intestinal absorption of glucose and its utilization. </li></ul><ul><li>4. Increases glycogenolysis & gluconeogenesis with an overall effect of increasing blood glucose level  hyperglycemia. </li></ul><ul><li>5. Lipid turn over and utilization are stimulated by T3 & T4. Hence hypothyroidism is associated with elevated cholesterol level. </li></ul><ul><li>6. Regulates water and electrolyte metabolism. </li></ul>