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GROWTH HORMONE

GROWTH HORMONE. D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM. GROWTH. MOST RAPID DURING PRENATAL PERIOD JUVENILE PERIOD: GH IS VERY IMPORTANT, BUT ALSO INSULIN AND THYROID HOMONE

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GROWTH HORMONE

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  1. GROWTH HORMONE D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY AND FACULTY MENTORING PROGRAM

  2. GROWTH • MOST RAPID DURING PRENATAL PERIOD • JUVENILE PERIOD: GH IS VERY IMPORTANT, BUT ALSO INSULIN AND THYROID HOMONE • ADOLESCENT: ANDROGENS AND ESTROGENS AS WELL-SPEED UP GROWTH AND BRING BONE GROWTH TO A HALT

  3. CONTROL OF GROWTH • GENETIC POTENTIAL • DIET • DISEASE • HORMONES

  4. LIVER SOMATOMEDINS BONE SOFT TISSUE GROWTH(ABOUT 30% OF THE GENETIC POTENTIAL) MANY TISSUES INTERMEDIARY METABOLISM INCREASE OR DECREASE ANTERIOR PITUITARY HORMONES: GROWTH HORMONE (SOMATOTROPIN)

  5. GROWTH HORMONE: SYNTHESIS, SECRETION, AND METABOLISM • ABOUT 1/6 OF THE AP CELLS • 5 - 10 MG STORED • 10X ANY OTHER PITUITARY HORMONE • TWO FORMS 22K AND 20K • BOUND TO PROTEIN IN BLOOD (SAME COMPOSITION AS RECEPTOR) • CANNOT ENTER CELL • DEGRADED IN TARGET CELLS AFTER UPTAKE BY RECEPTOR MEDIATED PROCESS

  6. METABOLIC ACTIONS OF GROWTH HORMONE • DECREASES SENSITIVITY OF MUSCLE AND FAT CELLS TO INSULIN • SENSITIZES BETA CELLS TO SIGNALS FOR INSULIN SECRETION (GET PROTEIN SYNTHESIS WITHOUTDECREASE IN BLOOD GLUCOSE) • MOBILIZES TRIGLYCERIDE FAT STORED IN ADIPOSE TISSUE • CONSERVES GLUCOSE FOR BRAIN • DIABETOGENIC EFFECT

  7. GH AND AGE • SECRETED THROUGHOUT LIFE • RATE DECREASES FROM 20-40 • MAY ACCOUNT FOR LOSS OF BODY MASS IN THE ELDERLY • CHANGES OCCUR IN BOTH FREQUENCY AND MAGNITUDE OF SECRETIONS

  8. GROWTH PROMOTING ACTIONS OF GROWTH HORMONE • SOFT TISSUES: STIMULATES CELL DIVISION, INCREASES SIZE OF CELLS • STIMULATES ALMOST ALL ASPECTS OF PROTEIN SYNTHESIS • INHIBITS PROTEIN DEGRADATION • PROMOTES UPTAKE OF AMINO ACIDS

  9. GROWTH PROMOTING ACTIONS OF GROWTH HORMONE • BONE: PROMOTES GROWTH OF LONG BONES • THICKNESS • LENGTH • AT END OF ADOLESCENCE, SEX HORMONES STOP THIS ACTION

  10. GROWTH HORMONE ACTS THROUGH SOMATOMEDINS • PEPTIDE MEDIATORS: SOMATOMEDINS • CLOSELY RELATED TO INSULIN-LIKE GROWTH FACTORS IGF-I AND IGF-II • PRODUCED IN LIVER AND OTHER TISSUES • ALSO PARACRINE EFFECTS

  11. REGULATION OF GROWTH HORMONE SECRETION HIGHER BRAIN CENTERS (+) (-) HYPOTHALAMUS GH-RH SST PITUITARY GH SOMATOMEDINS TARGET CELLS

  12. GHRH AND GHIH • ANTAGONIST IN CONTROL OF GROWTH HORMONE SECRETION • NEGATIVE FEEDBACK • DIURNAL RHYTHM: GH SECRETED AT NIGHT • EXERCISE, STRESS, HYPOGLYCEMIA

  13. ABNORMAL GH SECRETION • DEFICIENCY: DWARFISM, REDUCED MUSCLE STRENGTH, DECREASED BONE DENSITY • EXCESS:GIGANTISM, ACROMEGLY

  14. EPINEPHRINE, CORTISOL, AND GROWTH HORMONE • ALL INCREASE BLOOD GLUCOSE AND FATTY ACIDS • CORTISOL INCREASES BLOOD AA AND DECREASES MUSCLE PROTEIN • GH DECREASES BLOOD AA AND INCREASES MUSCLE PROTEIN

  15. EFFECTS OF GROWTH HORMONE ON BODY COMPOSITION • DEFICIENCY PROMOTES HIGHER PERCENTAGE OF FAT • PROMOTES GROWTH OF MUSCLE, SKIN, HEART, AND MOST INTERNAL ORGANS EXCEPT LIVER, SPLEEN, THYROID, GONADS, OR REPRODUCTIVE ORGANS.

  16. SYNERGISM OF GH WITH OTHER HORMONES • THYROID • INSULIN • GONADAL HORMONES • GLUCOCORTICOIDS • OTHER HORMONES AND GROWTH FACTORS

  17. THYROID AND GROWTH • GROWTH STUNTED IN ABSENCE • EXCESS MAY STIMULATE RATE BUT NOT DRAMATICALLY • PROMOTE GH SYNTHESIS • PERMISSIVE EFFECT ON GH AT TARGETS

  18. INSULIN • IMPORTANT DURING FETAL PERIOD IN CONTRAST TO GH AND THYROXINE • CHILDREN OF DIABETIC MOTHERS CAN BE LARGER • RELATED STRUCTURALLY TO THE SOMATOMEDINS • WITHOUT INSULIN, NORMAL RESPONSES TO GH ARE NOT SEEN • REGULATOR OF PROTEIN SYSNTHESIS? • REGULATOR OF ENERGY METABOLISM

  19. GONADAL HORMONES: ANDROGENS • LINEAR GROWTH BEFORE EPIPHYSIS FUSES • ENHANCED GH SECRETION • GROWTH OF MUSCLE: DOUBLING OF MUSCLE MASS IN BOYS AT PUBERTY (SIZE AND NUMBER OF MUSCLE CELLS) (GH AND THYROID NOT NEEDED FOR THIS) • LITTLE EFFECT IN ADULT MEN WITH NORMAL TESTICULAR FUNCTION

  20. GONADAL HORMONES: ESTROGENS • LINEAR GROWTH BEFORE EPIPHYSIS FUSES AND BEFORE BREAST GROWTH (BREAST GROWTH NEEDS HIGHER LEVELS) • MORE COMPLICATED THAN IN MALES

  21. GLUCOCORTICOIDS • ACUTELY GIVEN-ENHANCE GH GENE TRANSCRIPTION • COMPLEX EFFECTS ON GH SECRETION • OVERSECRETION IN CHILDREN MAY RESULT IN STUNTED GROWTH • ANTAGONIZE THE ACTIONS OF GH

  22. OTHER HORMONES AND GROWTH FACTORS • EPIDERMAL GROWTH FACTOR • PLATELET-DERIVED GF • TRANSFORMING GROWTH FACTORS • FIBROBLAST GFS • NERVE GF • CYTOKINES • SEE TABLE 1 IN TEXT

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