Growth Hormone Victoria Brown

Structure of hormone 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 Single-chain glycoprotein receptor 2 binding receptors for each molecule of growth hormone: GHRI GHRII 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? 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? 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 Growth hormone travels through the blood and stimulates the liver to produce a protein called insulin- like growth factor (IGF-1) In children, IGF-1 stimulates chondrocytes to multiply in the cartilage at the ends of long bones (epiphyseal plate) 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 Protein metabolism: Fat metabolism: Increased amino acid uptake Increased protein synthesis Fat metabolism: 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)

Primary Target tissues Bone Muscle Fat

Regulation 2 hormones from the hypothalamus: Growth hormone-releasing hormone (GHRH) Stimulates both the synthesis and secretion of growth hormone Somatostatin (SS) Inhibits 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 IGF-I Growth hormone Directly suppresses the somatotroph cells Stimulates the release of somatostatin from the hypothalamus Growth hormone Inhibits GHRH secretion

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Normal blood values 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? Usually from a tumor on the pituitary Begins before puberty Gigantism Robert Wadlow At birth: 8.5 lbs 5 years old: 5’ 4” and 105 lbs Adult: 8’ 11” and 490 lbs Begins after puberty Acromegaly Enlarged face, hands, and feet High blood pressure and heart disease A number of metabolic derangements, including hyperglycemia

Too little growth hormone? Begins before puberty: Dwarfism 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