THYROID HORMONE D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY

THE THYROID GLAND zOVER TRACHEA zTWO LARGE LATERAL LOBES CONNECTED BY AN ISTHMUS z15 to 20 g zFUNCTIONAL UNIT IS THE FOLLICLE: EPITHELIAL CELLS AROUND A HOLLOW VESSICLE FILLED WITH THYROGLOBULIN

THE THYROID HORMONES zTHYROGLOBULIN: STORAGE FORM BINDS HORMONES zTETRAIODOTHYRONINE zTRIIODOTHYRONINE zIODINE REQUIRED FROM DIETARY INTAKE

THYROID HORMONES o HOC - C - COOH B A I I I I H H NH 2 H o HOC - C - COOH B A II I H H NH 2 H THYROXINE TRIIODOTHYRONINE

THYROID HORMONE SYNTHESIS zDEPENDENT ON IODINE (IODINE PUMP CONCENTRATES IODINE IN CELLS) zDEPENDENT ON TYROSINE zPARTIALLY SYNTHESIZED (THYROGLOBULIN) EXTRACELLULARLY AT LUMINAL SURFACE OF FOLLICULAR CELLS AND STORED IN FOLLICULAR LUMEN

EFFECTS OF IODINE zDURING IODINE DEFICIENCY, HORMONE SYNTHESIS IS IMPAIRED zEXCESS IODINE ALSO INHIBITS SYSNTHESIS

THYROID HORMONE SECRETION zWITH TSH STIMULATION, ENDOCYTOSIS BRINGS THE THYROGLOBIN BACK INTO FOLLICULAR CELLS zTHYROGLOBULIN IS DEGRADED TO T 3 AND T 4

99% OF THYROID HORMONE IN THE BLOOD IS BOUND zTHYROXINE-BINDING GLOBULIN (TBG) zTHYROXINE-BINDING PREALBUMIN (TBPA) [TRANSTHYRETIN] zALBUMIN zABOUT THREE TIMES AS MUCH AS IS SECRETED AND DEGRADED IN A SINGLE DAY (BUFFER) zT 4 BINDS BETTER THAN T 3

THYROID HORMONE’S EFFECTS zMETABOLIC RATE: INCREASED BMR zCALOROGENIC: INCREASED HEAT PRODUCTION(OXIDATIVE METABOLISM) zSYMPATHOMIMETIC: FLIGHT OR FIGHT zCARDIOVASCULAR:INCREASES RESPONSIVENESS OF HEART zGROWTH: ESSENTIAL FOR NORMAL GROWTH OF SKELETAL SYSTEM (PERMISSIVE OR SYNERGYSTIC WITH GH, INSULIN-LIKE GROWTH FACTOR), CNS, ANS zNERVOUS SYSTEM:DEVELOPMENT AND ADULT ACTIVITY

METABOLIC EFFECTS OF THYROID HORMONE zCALOROGENIC EFFECT: INFLUENCES TOLERENCE TO COLD, AVAILABILITY OF ATP zCARBOHYDRATE METABOLISM: INCREASED GLUCOSE ABSORPTION FROM GUT,GLCOGENOLYSIS, GLUCONEOGENESIS, GLUCOSE OXIDATION. zLIPID METABOLISM: LIPOGENESIS IN ADIPOCYTES, IN COORDIMNATION WITH BLOOD GLUCOSE LEVELS

CONTROL OF FUEL METABOLISM zGLYCOGENESIS zGLYCOGENOLYSIS zGLUCONEOGENESIS zPROTEIN SYNTHESIS zPROTEIN DEGRADATION zFAT SYNTHESIS zFAT BREAKDOWN

GLYCOGENESIS zGLYCOGEN IS A BRANCHED POLYMER OF GLUCOSE STORED IN THE LIVER AND MUSCLE CELLS zSYNTHESIS IS BY SEPARATE PATHWAY FROM BREAKDOWN zHIGHLY REGULATED BY INSULIN

GLYCOGENOLYSIS zBREAKDOWN OF GLYCOGEN STORES INTO GLUCOSE zREGULATES BLOOD GLUCOSE BETWEEN MEALS zHOMONALLY CONTROLLED (GLUCAGON, EPINEHRINE, NOREPINEPHRINE AND CLUCOCORTICOIDS) AMPLIFIED BY THYROID HORMONE

GLUCONEOGENESIS zPRECURSORS ARE 3 AND 4 CARBON COMPOUNDS zVIA FRUCTOSE PHOSPHATE zGLUCAGON CONTROLLED AIDED BY THYROID HORMONE zMAIN PRECURSOR ALANINE AND OTHER AA

PROTEIN DEGRADATION zUSUALLY BALANCED BY SYNTHESIS zNO ENERGY STORES IN FORM OF PROTEIN zCAN BE ENHANCED BY GLUCAGON AND THYROID HORMONES LEADING TO GLUCONEOGENESIS

THYROID HORMONE EFFECTS ON NITROGEN METABOLISM zENHANCES BOTH SYNTHESIS AND DEGRADATION OF PROTEINS zEXCESS HORMONE PROMOTES DEGREDATION

FAT SYNTHESIS zGLUCOSE - FATTY ACID CYCLE zFATTY ACIDS PRODUCED CONSTANTLY IN ADIPOSE TISSUE. zBECOME FFA OR BECOME TRIGLYCERIDES DEPENDING ON  -GLYCEROL PHOSPHATE FROM GLUCOSE OXIDATION zNEED OPTIMAL AMOUNTS OF THYROID HORMONE

GLUCOSE - FATTY ACID CYCLE FATTY ACIDS TRIGLYCERIDES CO 2 GLUCOSE-6-P GLUCOSE FFA ADIPOCYTE MYOCYTE KETONES (-) BLOOD

THYROID AND TEMPERATURE REGULATION zT 3 IS THE DOMINANT FORM INVOLVED zEXPOSURE TO COLD CAUSES T 4 CONVERSION TO T 3. zPROMOTES CALOROGENIC EFFECT (LONG TERM COLD ADAPTATION) zSHORT TERM EFFECTS DUE TO SYMPATHETIC MIMETIC EFFECTS AND THE SHIVERING RESPONSE OF MUSCLES

REGULATION OF THYROID SECRETION HYPOTHALAMUS TRH ANTERIOR PITUITARY TSH THYROID GLAND TARGET ORGANS THYROID HORMONE STRESS COLD - +

EFFECTS OF TSH zGREATLY INCREASES ENDOGENOUS SYNTHESIS AND SECRETION OF HORMONE zINCREASES BLOOD FLOW zPLEIOTROPIC EFFECT ON GLANDULAR TISSUE, RNA AND DNA SYNTHESIS (HYPERPLASIA), PHOSPHOLIPID METABOLISM, ETC.

TSH MODE OF ACTION zRECEPTOR SPANS MEMBRANE zG-PROTEIN SUPERFAMILY zcAMP SECOND MESSENGER zINFLUENCES EVERY STEP OF THE HORMONE SYNTHESIS, STORAGE, AND SECRETION.

ABNORMALITIES OF THYROID FUNCTION zHYPO zREDUCED BMR zPOOR TOLERANCE OF COLD zGAIN OF WEIGHT zFATIGUE zSLOW, WEAK PULSE zSLOW REFLEXES AND MENTATION zMYXEDEMA zGOITER zCRETINISM z HYPER z GRAVE’S DISEASE:TSI (THYROID STIMULATING IMMUNOGLOBULIN- MIMICS TSH) z EXOPHTALMOS z GOITER