thyroid hormone d. c. mikulecky professor of physiology
TRANSCRIPT
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THYROID HORMONE
D. C. MIKULECKYPROFESSOR OF PHYSIOLOGY
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THE THYROID GLAND
OVER TRACHEATWO LARGE LATERAL LOBES
CONNECTED BY AN ISTHMUS15 to 20 gFUNCTIONAL UNIT IS THE FOLLICLE:
EPITHELIAL CELLS AROUND A HOLLOW VESSICLE FILLED WITH THYROGLOBULIN
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THE THYROID HORMONES
THYROGLOBULIN: STORAGE FORM BINDS HORMONES
TETRAIODOTHYRONINETRIIODOTHYRONINEIODINE REQUIRED FROM DIETARY
INTAKE
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THYROID HORMONES
oHO C - C - COOHB A
I
I
I
I
H
H NH2
H
oHO C - C - COOHB A
I I
I
H
H NH2
H
THYROXINE
TRIIODOTHYRONINE
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THYROID HORMONE SYNTHESIS
DEPENDENT ON IODINE (IODINE PUMP CONCENTRATES IODINE IN CELLS)
DEPENDENT ON TYROSINEPARTIALLY SYNTHESIZED
(THYROGLOBULIN) EXTRACELLULARLY AT LUMINAL SURFACE OF FOLLICULAR CELLS AND STORED IN FOLLICULAR LUMEN
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EFFECTS OF IODINE
DURING IODINE DEFICIENCY, HORMONE SYNTHESIS IS IMPAIRED
EXCESS IODINE ALSO INHIBITS SYSNTHESIS
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THYROID HORMONE SECRETION
WITH TSH STIMULATION, ENDOCYTOSIS BRINGS THE THYROGLOBIN BACK INTO FOLLICULAR CELLS
THYROGLOBULIN IS DEGRADED TO T3 AND T4
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99% OF THYROID HORMONE IN THE BLOOD IS BOUND
THYROXINE-BINDING GLOBULIN (TBG)THYROXINE-BINDING PREALBUMIN
(TBPA) [TRANSTHYRETIN]ALBUMIN ABOUT THREE TIMES AS MUCH AS IS
SECRETED AND DEGRADED IN A SINGLE DAY (BUFFER)
T4 BINDS BETTER THAN T3
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THYROID HORMONE’S EFFECTS
METABOLIC RATE: INCREASED BMR CALOROGENIC: INCREASED HEAT
PRODUCTION(OXIDATIVE METABOLISM) SYMPATHOMIMETIC: FLIGHT OR FIGHT CARDIOVASCULAR:INCREASES RESPONSIVENESS OF
HEART GROWTH: ESSENTIAL FOR NORMAL GROWTH OF
SKELETAL SYSTEM (PERMISSIVE OR SYNERGYSTIC WITH GH, INSULIN-LIKE GROWTH FACTOR), CNS, ANS
NERVOUS SYSTEM:DEVELOPMENT AND ADULT ACTIVITY
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METABOLIC EFFECTS OF THYROID HORMONE
CALOROGENIC EFFECT: INFLUENCES TOLERENCE TO COLD, AVAILABILITY OF ATP
CARBOHYDRATE METABOLISM: INCREASED GLUCOSE ABSORPTION FROM GUT,GLCOGENOLYSIS, GLUCONEOGENESIS, GLUCOSE OXIDATION.
LIPID METABOLISM: LIPOGENESIS IN ADIPOCYTES, IN COORDIMNATION WITH BLOOD GLUCOSE LEVELS
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CONTROL OF FUEL METABOLISM
GLYCOGENESISGLYCOGENOLYSISGLUCONEOGENESISPROTEIN SYNTHESISPROTEIN DEGRADATIONFAT SYNTHESISFAT BREAKDOWN
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GLYCOGENESIS
GLYCOGEN IS A BRANCHED POLYMER OF GLUCOSE STORED IN THE LIVER AND MUSCLE CELLS
SYNTHESIS IS BY SEPARATE PATHWAY FROM BREAKDOWN
HIGHLY REGULATED BY INSULIN
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GLYCOGENOLYSIS
BREAKDOWN OF GLYCOGEN STORES INTO GLUCOSE
REGULATES BLOOD GLUCOSE BETWEEN MEALS
HOMONALLY CONTROLLED (GLUCAGON, EPINEHRINE, NOREPINEPHRINE AND CLUCOCORTICOIDS) AMPLIFIED BY THYROID HORMONE
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GLUCONEOGENESIS
PRECURSORS ARE 3 AND 4 CARBON COMPOUNDS
VIA FRUCTOSE PHOSPHATEGLUCAGON CONTROLLED AIDED
BY THYROID HORMONEMAIN PRECURSOR ALANINE AND
OTHER AA
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PROTEIN DEGRADATION
USUALLY BALANCED BY SYNTHESISNO ENERGY STORES IN FORM OF
PROTEINCAN BE ENHANCED BY GLUCAGON
AND THYROID HORMONES LEADING TO GLUCONEOGENESIS
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THYROID HORMONE EFFECTS ON NITROGEN METABOLISM
ENHANCES BOTH SYNTHESIS AND DEGRADATION OF PROTEINS
EXCESS HORMONE PROMOTES DEGREDATION
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FAT SYNTHESIS
GLUCOSE - FATTY ACID CYCLEFATTY ACIDS PRODUCED
CONSTANTLY IN ADIPOSE TISSUE. BECOME FFA OR BECOME
TRIGLYCERIDES DEPENDING ON -GLYCEROL PHOSPHATE FROM GLUCOSE OXIDATION
NEED OPTIMAL AMOUNTS OF THYROID HORMONE
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GLUCOSE - FATTY ACID CYCLE
FATTYACIDS
TRIGLYCERIDES
CO2
GLUCOSE-6-P
GLUCOSE
FFA
ADIPOCYTE MYOCYTE
KETONES(-)
(-)BLOOD
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THYROID AND TEMPERATURE REGULATION
T3 IS THE DOMINANT FORM INVOLVED
EXPOSURE TO COLD CAUSES T4 CONVERSION TO T3 .
PROMOTES CALOROGENIC EFFECT (LONG TERM COLD ADAPTATION)
SHORT TERM EFFECTS DUE TO SYMPATHETIC MIMETIC EFFECTS AND THE SHIVERING RESPONSE OF MUSCLES
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REGULATION OF THYROID SECRETION
HYPOTHALAMUS
TRH
ANTERIOR PITUITARY
TSH
THYROID GLAND
TARGET ORGANSTHYROID HORMONE
STRESSCOLD
- +
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EFFECTS OF TSH
GREATLY INCREASES ENDOGENOUS SYNTHESIS AND SECRETION OF HORMONE
INCREASES BLOOD FLOWPLEIOTROPIC EFFECT ON
GLANDULAR TISSUE, RNA AND DNA SYNTHESIS (HYPERPLASIA), PHOSPHOLIPID METABOLISM, ETC.
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TSH MODE OF ACTION
RECEPTOR SPANS MEMBRANEG-PROTEIN SUPERFAMILYcAMP SECOND MESSENGERINFLUENCES EVERY STEP OF THE
HORMONE SYNTHESIS, STORAGE, AND SECRETION.
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ABNORMALITIES OF THYROID FUNCTION
HYPO REDUCED BMR POOR TOLERANCE OF
COLD GAIN OF WEIGHT FATIGUE SLOW, WEAK PULSE SLOW REFLEXES AND
MENTATION MYXEDEMA GOITER CRETINISM
HYPER GRAVE’S DISEASE:TSI
(THYROID STIMULATING IMMUNOGLOBULIN-MIMICS TSH)
EXOPHTALMOS GOITER