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Sherwood Lectures, Fig. 19-1a, p. 692
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Regulation andRegulation and
Functions of the ThyroidFunctions of the Thyroid
HormonesHormones
Dr. Eeman AtDr. Eeman At--TarasTaras
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ObjectivesObjectives
Describe the mechanism of action of TSH at theDescribe the mechanism of action of TSH at thelevel of follicular cells in the thyroid glandlevel of follicular cells in the thyroid gland
Discuss the role of TSH in thyroid hormoneDiscuss the role of TSH in thyroid hormoneformation and its effect on the thyroid glandformation and its effect on the thyroid gland
Describe the mechanism of action of thyroidDescribe the mechanism of action of thyroidhormones on target cellshormones on target cells
Discuss the functions of thyroid hormones inDiscuss the functions of thyroid hormones indifferent body tissuesdifferent body tissues
List characteristic signs and symptoms related toList characteristic signs and symptoms related tohypothyroidism and hyperthyroidismhypothyroidism and hyperthyroidism
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Functions of the Thyroid GlandFunctions of the Thyroid Gland
Synthesis and secretion ofSynthesis and secretion ofthyroid hormonesthyroid hormones(triiodothyronine, T(triiodothyronine, T33 andandthyroxine, Tthyroxine, T44))
The thyroid concentratesThe thyroid concentratesiodide (iodide (3030::11))
Stores thyroid hormones inStores thyroid hormones in
thyroglobulin (forthyroglobulin (forcompensation during times ofcompensation during times ofscarcity)scarcity) can store up tocan store up to 33months worth of thyroidmonths worth of thyroidhormoneshormones
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Tortora and Derrickson, 2006
The
HypothalamicPituitary
Thyroid Axis
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Mechanism of Action of Thyrotropin (TSH)Mechanism of Action of Thyrotropin (TSH)
TSH ReceptorAdenyl cyclase
G protein
TSH
TSH also increased follicular cell growth and development
Secretion of
T3 and T4
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SynthesisSynthesis
andandSecretionSecretion
of Thyroidof Thyroid
HormoneHormone
Tortora and Derrickson, 2006
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Synthesis and Secretion of Thyroid HormoneSynthesis and Secretion of Thyroid Hormone
11.. Active transport of iodide across the basement membrane (iodideActive transport of iodide across the basement membrane (iodide
trapping)trapping)
22. Synthesis of thyroglobulin. Synthesis of thyroglobulin
33--44. Oxidation of iodide and iodination of tyrosyl residues in thyroglobulin. Oxidation of iodide and iodination of tyrosyl residues in thyroglobulin
55. Coupling of iodotyrosin molecules (within thyroglobulin). Coupling of iodotyrosin molecules (within thyroglobulin) TT44 and Tand T33
66. Proteolysis of thyroglobulin. Proteolysis of thyroglobulin
a. Deiodination of iodotyrosine within the thyroid cell; free iodide isa. Deiodination of iodotyrosine within the thyroid cell; free iodide is
reusedreused
b. Intrathyroidal deiodination of Tb. Intrathyroidal deiodination of T44 to Tto T33
77. Secretion of thyroid hormones. Secretion of thyroid hormones
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Thyroid Hormones and PotencyThyroid Hormones and Potency
Modifications ofModifications of
tyrosinetyrosine
TT44 normally convertednormally converted
to Tto T33 prior to receptorprior to receptor
bindingbinding
TT33 is more potentis more potent
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Effects of TSHEffects of TSH
Increase iodine pump activityIncrease iodine pump activity
Increase synthesis ofIncrease synthesis of thyroglobulinthyroglobulin
Increase activity of thyroidIncrease activity of thyroid peroxidaseperoxidase
IodinationIodination
Coupling of tyrosine residuesCoupling of tyrosine residues
Increases proteolysis ofIncreases proteolysis of thyroglobulinthyroglobulin (and(and
release of thyroid hormone)release of thyroid hormone)
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Mechanism of Thyroid Hormone ActionMechanism of Thyroid Hormone Action
Increased transcription
of many genes
Increased synthesis of
many proteins: structural
proteins, transport
proteins
Net result: increase in
functional activity in
many parts of the body
>90% T3
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Mechanism of Action of Thyroid
Hormones
The action of thyroidhormones is of slowonset latent period
Latency is likely due totheir binding to plasmaand cellular proteins
Prolonged action
T3 is faster-acting thanT4 has a shorter half-life
Guyton and Hall, 2006
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Thyroid Hormone StimulatesThyroid Hormone Stimulates
Synthesis of ProteinsSynthesis of Proteins
Costanzo, 3rd edition, studentconsult.com
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Mechanism of Action of ThyroidMechanism of Action of Thyroid
HormoneHormone Targets most body cellsTargets most body cells
Responsiveness correlates to the numberResponsiveness correlates to the number
of receptorsof receptors
Direct actionsDirect actions
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Thyroid Hormones Increase the BasalThyroid Hormones Increase the Basal
Metabolic RatesMetabolic Rates
Increase cellular metabolicIncrease cellular metabolicactivity of most tissues in theactivity of most tissues in thebodybody
6060 toto 100100% increase in basal% increase in basalmetabolic ratemetabolic rate
Utilization of food for energy isUtilization of food for energy isacceleratedaccelerated
Corresponding increase inCorresponding increase inprotein catabolismprotein catabolism
Increased ATP formationIncreased ATP formation(increased mitochondria)(increased mitochondria)
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Effects of Thyroid HormonesEffects of Thyroid Hormones
Increase in active transport of ions throughIncrease in active transport of ions through
cell membranescell membranes
Eg. NaEg. Na++--KK++ ATPase enzymeATPase enzyme
Uses energy and generates heatUses energy and generates heat
Increased transport of Na into cellsIncreased transport of Na into cells
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Thyroid Hormone, Growth andThyroid Hormone, Growth and
DevelopmentDevelopment In infants andIn infants and
childrenchildren
Promotes growthPromotes growth Brain developmentBrain development
Thyroid hormoneThyroid hormone
stimulates thestimulates the
expression of theexpression of thegene for GHgene for GH
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Thyroid Hormone Induced ReleaseThyroid Hormone Induced Release
of Fatty Acids from Adipocytesof Fatty Acids from Adipocytes
Thyroid hormoneThyroid hormone
increases the numberincreases the number
of epinephrineof epinephrine
receptorsreceptors thisthis
potentiates the effectpotentiates the effect
of epinephrine onof epinephrine on
lipolysislipolysis
Vander et al, 8th edition, McGraw-Hill
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Effects of Thyroid HormonesEffects of Thyroid Hormones Stimulates carbohydrate metabolismStimulates carbohydrate metabolism
Increases plasma glucose and thereby stimulatesIncreases plasma glucose and thereby stimulates
insulin secretioninsulin secretion
Stimulation of fat metabolismStimulation of fat metabolism
Increased mobilization of lipids, lipolysisIncreased mobilization of lipids, lipolysis
Increases FFA in plasma but decreasesIncreases FFA in plasma but decreasescholesterol, phospholipids and triglyceridescholesterol, phospholipids and triglycerides
Increases need for vitamins (needed forIncreases need for vitamins (needed for
enzymes)enzymes)
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Thyroid Hormones and theThyroid Hormones and the
Cardiovascular SystemCardiovascular System
Increased blood flow and cardiac outputIncreased blood flow and cardiac output
Increased heart rateIncreased heart rate
Increased strength of myocardialIncreased strength of myocardialcontractioncontraction
Lower peripheral vascular resistanceLower peripheral vascular resistance
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Excess Thyroid HormonesExcess Thyroid Hormones
Decreases body weightDecreases body weight
Increases appetiteIncreases appetite
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Sherwood images, Fig. 19-6, p. 697
Goiter
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Thyroid DysfunctionThyroid Dysfunction
Sherwood images, Table 19-1, p. 696
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GoitersGoiters
Dramatic enlargement of the thyroid glandDramatic enlargement of the thyroid gland
Excessive production of TSH due toExcessive production of TSH due to
absence of negative feedback from theabsence of negative feedback from thethyroid hormones (hypothyroidism)thyroid hormones (hypothyroidism)
Iodine deficiencyIodine deficiency
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Hypothyroidism:Hypothyroidism:
Signs and SymptomsSigns and Symptoms FatigueFatigue
Extreme somnolenceExtreme somnolence
Muscular sluggishnessMuscular sluggishness
Slowed heart rateSlowed heart rate
Decreased cardiac outputDecreased cardiac output
Decreased blood volumeDecreased blood volume Mental sluggishnessMental sluggishness
ConstipationConstipation
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GoiterGoiter
Autoimmune disease (Graves)Autoimmune disease (Graves)
TSH receptor is activated by antibodies (longTSH receptor is activated by antibodies (long--acting thyroid stimulators, LATS)acting thyroid stimulators, LATS)
Leads to excessive thyroid hormone synthesis andLeads to excessive thyroid hormone synthesis and
overgrowth of the thyroid glandovergrowth of the thyroid gland
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Sherwood images, Fig. 19-4, p. 696
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HyperthyroidismHyperthyroidism
Signs and SymptomsSigns and Symptoms
Weight lossWeight loss
Increased appetiteIncreased appetite
Nervousness and anxietyNervousness and anxiety
ExophthalamusExophthalamus
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QuestionsQuestions
What essential nutrient is needed for synthesis of thyroidWhat essential nutrient is needed for synthesis of thyroidhormones?hormones?
Describe the sequence of events that occurs when thyroidDescribe the sequence of events that occurs when thyroidhormones bind to their receptor.hormones bind to their receptor.
A person with symptoms of hypothyroidism (e.g.A person with symptoms of hypothyroidism (e.g.sluggishness, intolerance to cold) is found to have abnormallysluggishness, intolerance to cold) is found to have abnormallylow plasma concentrations of Tlow plasma concentrations of T44, T, T33 and TSH. After anand TSH. After aninjection of TRH, the plasma concentrations of all threeinjection of TRH, the plasma concentrations of all three
hormones increase. In this case where is the site of thehormones increase. In this case where is the site of thedefect that lead to the hypothyroidism?defect that lead to the hypothyroidism?
Iodide in the thyroid gland is mainly stored as:Iodide in the thyroid gland is mainly stored as:
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ReferencesReferences
Guyton and Hall. Textbook ofMedicalGuyton and Hall. Textbook ofMedical
Physiology ,Physiology , 1111thth edition.edition.
Greenspan and Gardner. Basic andGreenspan and Gardner. Basic and
Clinical Endocrinology,Clinical Endocrinology, 77thth edition.edition.
http://msjensen.cehd.umn.edu/http://msjensen.cehd.umn.edu/11351135/links/A/links/A
nimations/Flash/nimations/Flash/00230023--swf_intracellular_.swfswf_intracellular_.swf