Thyroid Hormones Females
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Thyroid Hormones Females

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Thyroid Hormones Females Thyroid Hormones Females Presentation Transcript

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