Transcript THE ENDOCRINE SYSTEM

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