7- regulation and functions of the thyroid hormones

8/7/2019 7- Regulation and Functions of the Thyroid Hormones

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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

7- regulation and functions of the thyroid hormones

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