GROWTH HORMONE

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GROWTH HORMONE

• D. C. MIKULECKY
• PROFESSOR OF PHYSIOLOGY
• AND
• FACULTY MENTORING PROGRAM

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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

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CONTROL OF GROWTH

• GENETIC POTENTIAL
• DIET
• DISEASE
• HORMONES

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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

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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

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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

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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

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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

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GROWTH PROMOTING ACTIONS OF GROWTH HORMONE

• BONE PROMOTES GROWTH OF LONG BONES
• THICKNESS
• LENGTH
• AT END OF ADOLESCENCE, SEX HORMONES STOP THIS
  ACTION

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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

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REGULATION OF GROWTH HORMONE SECRETION
HIGHER BRAIN CENTERS
()
(-)
HYPOTHALAMUS
GH-RH
SST
PITUITARY
GH
SOMATOMEDINS
TARGET CELLS
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GHRH AND GHIH

• ANTAGONIST IN CONTROL OF GROWTH HORMONE SECRETION
• NEGATIVE FEEDBACK
• DIURNAL RHYTHM GH SECRETED AT NIGHT
• EXERCISE, STRESS, HYPOGLYCEMIA

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ABNORMAL GH SECRETION

• DEFICIENCY DWARFISM, REDUCED MUSCLE STRENGTH,
  DECREASED BONE DENSITY
• EXCESSGIGANTISM, ACROMEGLY

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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

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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.

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SYNERGISM OF GH WITH OTHER HORMONES

• THYROID
• INSULIN
• GONADAL HORMONES
• GLUCOCORTICOIDS
• OTHER HORMONES AND GROWTH FACTORS

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THYROID AND GROWTH

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

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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

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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

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GONADAL HORMONES ESTROGENS

• LINEAR GROWTH BEFORE EPIPHYSIS FUSES AND BEFORE
  BREAST GROWTH (BREAST GROWTH NEEDS HIGHER LEVELS)
• MORE COMPLICATED THAN IN MALES

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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

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OTHER HORMONES AND GROWTH FACTORS

• EPIDERMAL GROWTH FACTOR
• PLATELET-DERIVED GF
• TRANSFORMING GROWTH FACTORS
• FIBROBLAST GFS
• NERVE GF
• CYTOKINES
• SEE TABLE 1 IN TEXT