Physiology Block 3 Week 14 09 Growth Hormone Flashcards
What are the three hormones of the somatomammatropin family?
Prolactin
Growth Hormone
Human placental lactogen (hPL)
Prolactin and growth hormone have sequence homology and don’t usually bind each other’s recepots
hPL may have some growth hormone-like effects in the pregnant woman
Direct Effect of Human Growth Hormone (via insulin-like growth factor 1 [IGF1])
Primarily effects on intermediate metabolism
Direct effects on:
- adipose tissue
- liver
- muscle
Human Growth Hormone effect on Adipose Tissue
Decreased glucose uptake
Increased lypolysis
Decreased Adiposity
Human Growth Hormone effect on Liver
Increased gluconeogenesis
Increased IGF1
Human Growth Hormone effect on Muscle
Decreased glucose uptake
Increased AA uptake
Increase in protein synthesis
Increased lean body mass
Indirect effect of Human Growth Hormone
Growth promoting effects of GH are mediated by insulin-like Growth factor 1
IGF1 coordinates organ growth and linear growth rates in children
Produced by Liver
Human Growth Hormone effect on Bone, Heart, Lung
IGF1 from liver works on these
Increased protein synthesis increased DNA+RNA expression Increased cell size/number Increased organ size Increased organ function
Human Growth Hormone effect on Chondrocytes
IGF1 from liver works on this
Increased AA uptake Increased protein synthesis Increased DNA+RNA expression Increased collagen Increased cell size and number Increased linear growth
Human Growth Hormone effect on Muscle
IGF1 from liver also works on this (indirect) in addition to Growth Hormone (direct)
Decreased glucose uptake
Increased AA uptake
Increase in protein synthesis
Increased lean body mass
Growth hormone effect on children
Infantile growth is NOT controlled by growth hormone–works through IGF1
In fetus, GH does have growth promoting effects
Fetal Growth Regulation
GH (direct, not thru IGFs)
IGF-1 (early); IGF-1 (late)
Epidermal and fibroblast growth factor
Maternal thyroid hormone needed in 1st trimester
Why is insulin important in fetal growth?
Macrosomy–Birth to large infants when mother has hyperglycemia (with uncontrolled diabetes mellitus)
Mom has high plasma glucose–crosses placenta over to the fetus
Fetus releases insulin
–the release of insulin triggers fetal growth
Growth Spurt
Gonadal (sex) steroids from ovaries or testes have two major effects:
- activation of the pubertal growth spurt by stimulating growth hormone release
- terminates pubertal growth spurt by inducing closure of the epiphyseal growth plates in the long bones
Stimulation of Growth Hormone
Amino Acids (acute): -building new tissue
Starvation (chronic):
-counterregulatory support of blood glucose
Hypoglycemia:
-counterregulatory
Exercise:
-promoting new muscle growth
Stage 3/4 sleep:
-children with sleep deprivation often have failure to thrive
Gonadal steroids/Thyroid Hormone
Inhibition of Growth Hormone
Glucose, GH, IGF1 inhibit GH release via negative feedback
Cortisol:
-periods of stress limit growth to divert calories for survival
What test could you devise to evaluate a 3 year old child for growth hormone deficiency?
Amino Acid stimulation (Arginine Infusion)
Exercise stress test
Sleep Study and pull GH when stage 3/4 sleep
Growth Hormone Secretion Control
Secretion of GH is controlled by neural and hormonal input into specific hypothalamic nuclei
Stimulatory: GH-RH
Inhibitory: Somatostatin
GH stimulates target cells (liver to produce IGF-1)
IGF-1:
- directly inhibits GH release from pituitary
- inhibits GL-RH release from hypothalamus
- stimulates somatostatin release (inhibits GH release at pituitary)
GH:
- inhibits GH-RH release at hypothalamus
- GH stimulates somatostatin (inhibits GH release at pituitary)
Linear Growth Velocity and Weight Gain Rate from Birth to End of Puberty
Rates greatest at birth
Between 2-onset of Puberty, GH/Thyroid Hormone is necessary for normal growth rate
Female growth spurt earlier in females–estrogen
Growth spurt terminated by effect of gonadal steroids on growth plates of long bones–earlier in females
Linear growth compete by end of puberty
Excess Growth Hormone
What is a screening test?
What is a treatment?
Almost always due to pituitary GH-secreting tumor
Gigantism–before puberty
Acromegaly (joints on hands and feet = coarse features)–after puberty
Screening test–IGF-1 (only works when excess GH)
Treatment:
- remove tumor
- somatostatin analog–shrinks the tumor
Deficient Growth Hormone
What is a screening test?
What is a treatment?
Short stature–children
Adults–hypopituitary patients have GH deficiency
Screening:
- Arginine test
- exercise study
- sleep study
Treatment: Recombinant human GH injections
What would the effect of a somatostatin releasing tumor be?
It would lead to GH deficiency and short stature in children
Cushing’s Syndrome effect on growth
Inhibition of GH by cortisol or glucocorticoid
Hypothalamus
- stimulates somatostatin
- inhibits GHRH release
Pituitary
-inhibits pulsatile GH release
Bone
- inhibits growth plate response to IGF-1
- inhibits collagen synthesis
Other
-inhibit GnRH/ LH-FSH/ Androgen release (men)
Ex. Gary Coleman was on prednisone (glucocorticoid analog) after kidney transplant in order to suppress immune response
–resulted in GH deficiency
Which of the following will lead to an increase in growth hormone secretion?
A tumor producing IGF-1
An analog of somatostatin.
An antagonist of somatostatin.
An infusion of glucose
An antagonist of somatostatin.
