Transcript Growth hormone-releasing hormone

GROWTH HORMONE
Victoria Brown
Structure of hormone
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191 amino acids long
Protein structure
4 helices that help it
bind its receptor
2 strong sulfide bonds
hold the structure
together
Structure of receptor
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Single-chain glycoprotein receptor
2 binding receptors for each molecule of growth
hormone:
GHRI
 GHRII
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The 2 receptor molecules bind to two structurally distinct
sites on opposite sides of a single growth hormone
molecule
Binding of the two receptors is sequential, not
simultaneous
Where does it come from?
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Synthesized and secreted by somatotroph cells
(anterior pituitary) in response to growth-hormone
releasing hormone (GHRH) from the hypothalamus
 Activates
gene transcription by cyclic adenosine
monophosphate (cAMP) mechanisms
What happens in the cell?
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The hormone binds on the outside of the cell, bringing
two receptors together
The interaction of growth hormone with its receptor
leads to activation of cytoplasmic tyrosine kinases,
triggering several enzymatic reactions and signaling
processes that stimulate growth
Role in growth
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Growth hormone travels through the blood and
stimulates the liver to produce a protein called insulinlike growth factor (IGF-1)
In children, IGF-1 stimulates chondrocytes to multiply in
the cartilage at the ends of long bones (epiphyseal
plate)
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This leads to growth in the length of the bones and increases
the child's height
In adults, growth hormone plays an important role in
repair and maintenance of the body’s tissues
IGF-1 also acts on immature muscle cells to increase
muscle mass
Role in metabolism
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Protein metabolism:
Increased amino acid uptake
 Increased protein synthesis
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Fat metabolism:
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Triglyceride breakdown in adipocytes (lipolysis)
Carbohydrate metabolism:
Helps maintain blood glucose levels
 Suppresses insulin to prevent uptake of glucose in peripheral
tissues
 Glucose synthesis in the liver (gluconeogenesis)
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Primary Target tissues
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Bone
Muscle
Fat
Regulation
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2 hormones from the hypothalamus:
 Growth
hormone-releasing hormone (GHRH)
 Stimulates
both the synthesis and secretion of growth
hormone
 Somatostatin
 Inhibits
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(SS)
growth hormone release from somatotroph cells
1 hormone from the stomach:
 Ghrelin
 Binds
to receptors on somatotroph cells and potently
stimulates secretion of growth hormone
Negative Feedback
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IGF-I
 Directly
suppresses the somatotroph cells
 Stimulates the release of somatostatin from the
hypothalamus
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Growth hormone
 Directly
suppresses the somatotroph cells
 Inhibits GHRH secretion
Feedback
Normal blood values
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1 - 9 ng/mL (male)
1 - 16 ng/mL (female)
Natural levels of growth hormone fluctuate during
the day, depending on:
 Stress
 Exercise
 Nutrition
 Sleep
Too much growth hormone?
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Usually from a tumor on the
pituitary
Begins before puberty
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Gigantism
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Robert Wadlow
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At birth: 8.5 lbs
5 years old: 5’ 4” and 105 lbs
Adult: 8’ 11” and 490 lbs
Begins after puberty
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Acromegaly
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Enlarged face, hands, and feet
High blood pressure and heart
disease
A number of metabolic
derangements, including
hyperglycemia
Too little growth hormone?
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Begins before puberty:
 Dwarfism
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Begins after puberty:
 Reduction
of
muscle/bone strength
and mass among other
debilitating factors
“There are no great limits to growth because there
are no limits of human intelligence, imagination, and
wonder.”
—Ronald Reagan