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

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 inrepair and maintenance of the body’s tissues

IGF-1 also acts on immature muscle cells to increase muscle mass

Role in growth

Role in metabolism

Protein 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 Directly suppresses the somatotroph cells Stimulates the release of somatostatin from

the hypothalamus Growth hormone

Directly suppresses the somatotroph cells Inhibits GHRH secretion

Feedback

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