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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 ADOLESCENT: ANDROGENS AND ESTROGENS AS WELL-SPEED UP GROWTH AND BRING BONE GROWTH TO A HALT CONTROL OF GROWTH GENETIC POTENTIAL DIET DISEASE HORMONES ANTERIOR PITUITARY HORMONES: GROWTH HORMONE (SOMATOTROPIN) LIVER SOMATOMEDINS BONE SOFT TISSUE GROWTH(ABOUT 30% OF THE GENETIC POTENTIAL) MANY TISSUES INTERMEDIARY METABOLISM INCREASE OR DECREASE 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 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 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 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 GROWTH PROMOTING ACTIONS OF GROWTH HORMONE BONE: PROMOTES GROWTH OF LONG BONES THICKNESS LENGTH AT END OF ADOLESCENCE, SEX HORMONES STOP THIS ACTION 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 REGULATION OF GROWTH HORMONE SECRETION HIGHER BRAIN CENTERS (+) (-) HYPOTHALAMUS GH-RH SST PITUITARY GH SOMATOMEDINS TARGET CELLS GHRH AND GHIH ANTAGONIST IN CONTROL OF GROWTH HORMONE SECRETION NEGATIVE FEEDBACK DIURNAL RHYTHM: GH SECRETED AT NIGHT EXERCISE, STRESS, HYPOGLYCEMIA ABNORMAL GH SECRETION DEFICIENCY: DWARFISM, REDUCED MUSCLE STRENGTH, DECREASED BONE DENSITY EXCESS:GIGANTISM, ACROMEGLY 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 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. SYNERGISM OF GH WITH OTHER HORMONES THYROID INSULIN GONADAL HORMONES GLUCOCORTICOIDS OTHER HORMONES AND GROWTH FACTORS THYROID AND GROWTH GROWTH STUNTED IN ABSENCE EXCESS MAY STIMULATE RATE BUT NOT DRAMATICALLY PROMOTE GH SYNTHESIS PERMISSIVE EFFECT ON GH AT TARGETS 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 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 GONADAL HORMONES: ESTROGENS LINEAR GROWTH BEFORE EPIPHYSIS FUSES AND BEFORE BREAST GROWTH (BREAST GROWTH NEEDS HIGHER LEVELS) MORE COMPLICATED THAN IN MALES 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 OTHER HORMONES AND GROWTH FACTORS EPIDERMAL GROWTH FACTOR PLATELET-DERIVED GF TRANSFORMING GROWTH FACTORS FIBROBLAST GFS NERVE GF CYTOKINES SEE TABLE 1 IN TEXT