GH and IGF on growth

Where is GH produced?

Anterior pituitary.

What stimulates and inhibits GH release?

Stimulated by GHRH; inhibited by somatostatin.

When is GH released?

In 6–8 pulses per night, especially during sleep.

What is GH’s primary target organ?

Liver, but also acts on muscle, bone, and fat.

What does GH do to adipose tissue?

Reduces lipogenesis and increases lipolysis.

What happens to growth in rodents without a pituitary gland (Hypox)?

Growth is reduced.

How is growth restored in Hypox animals?

Injection of pituitary extract (GH).

Is GH species-specific?

Yes—activity depends on similarity of receptor binding.

What are the effects of rPST (GH) in pigs?

Increased muscle and decreased fat.

What is IGF-1?

A 70-aa peptide similar to insulin that mediates GH effects.

What tissues produce IGF-1?

Mainly liver, but also bone and muscle.

What is the main receptor for IGF-1?

IGF1R.

What do IGFBPs do?

Regulate and buffer IGF activity.

Which IGFBP is most abundant in circulation?

IGFBP-3.

What happens when IGFBP is absent?

Free IGF can cause effects like hypoglycemia. (Low bloodsugar.)

Which has greater growth impact: endocrine or local IGF?

Paracrine/autocrine (local) IGF.

What is the liver’s IGF mainly used for?

Feedback to the pituitary to regulate GH.

What drives fetal growth: GH or IGF?

IGF (driven by nutrients and insulin).

What organ produces fetal IGF early and late in gestation?

Early: placenta; Late: fetal liver.

Is fetal GH required for fetal growth?

No. GH is present but not essential.

When is IGF-II more prevalent?

In the fetus, declines after birth.

Are IGF-II and IGF2R imprinted genes?

Yes—IGF2 = paternal, IGF2R = maternal in mice.

What stimulates liver IGF-1 production postnatally?

GH.

What tissues does IGF-1 act on?

Bone, muscle, and adipose via IGF1R.

What tissues also have GH receptors?

Muscle, bone, fat → direct and indirect GH effects.

What factors increase GH release?

Sleep, exercise, nutrition, sex steroids, ghrelin. (hunger hormone)

What inhibits GH release?

Stress, glucocorticoids, high IGF-1 (feedback).

What are positive physiological conditions for growth?

GH, insulin, glucose, amino acids.

What are negative feedback conditions?

High IGF-1, high free fatty acids, chronic GH.

GH/IGF Effects by Liver

↑ IGF-1, ↑ glucose, ↓ insulin sensitivity

GH/IGF Effects by Muscle

↑ Protein synthesis, ↑ glucose uptake

GH/IGF Effects by Adipose

↓ Lipogenesis, ↑ lipolysis

What does GH do before puberty?

Stimulates long bone growth.

What ends bone growth at puberty?

Estrogen closes the growth plates.

What happens with excess GH before puberty?

Gigantism

What happens with excess GH after puberty?

Acromegaly

What happens with too little GH before puberty?

Dwarfism or miniature size with normal proportions.

Insulin-Dependent Tissues

• Muscle

  • Uses: Fatty acids and glucose

  • Insulin action: Stimulates glucose uptake and glycogen storage

• Adipose (Fat)

  • Uses: Glucose

  • Insulin action: Stimulates glucose uptake and regulates fatty acid release

Not Insulin-Dependent Tissues

• Brain

  • Fuel: Glucose only (no glycogen storage)

  • Note: Glucose uptake is insulin-independent

• Liver

  • Function: Stores glycogen and releases glucose

  • Glucose uptake: Driven by glucose concentration, not insulin

  • Fuel: Ketoacids from amino acid breakdown