Growth hormone

 

Growth hormone

• Two types: 22K hGH (75%) and 20K hGH (10%)
• Halflife = 6-20mins.
  * Probably metabolised in liver.
• Two binding sites on the growth hormone molecule
  - binding of one site to a receptor leads to encourages binding of the other site to another receptor
  - Dimerisation is essential for receptor activation
• Comes in spikes throughout the day

Action of growth hormone

• Protein anabolism
  * positive nitrogen response
• Ketogenic and lipolysis
  --> increase FFA, and decrease in body fat store
• Antidiabetogenic
  * Increase hepatic glucose output
  * Anti-insulin effect in muslces
• Increase pancreatic B cell sensitivity
  --> increased insulin secretion
• Reduced Na+ and K+ renal excretion
• Increased Ca2+ absorption from GIT
• Positive PO4 balance
• Epiphysial growth
• Increase metabolic rate
• Stimulates IGF-1 production
• Intrinsic lactogenic acitivity
  * 4% of acromegaly develops lactation

 

Insulin-like growth factor I (IGF-I, Somatomedin C)

Produced by liver

Increases in childhood and peaks at 13-17 yo

 

• Increase skeletal and cartilage growth
• Protein synthesis
• Anti-lipolitic activity
  * opposite to hGH
• Insulin-like activity
  * opposite to hGH

 

Insulin-like growth factor II (IGF-II)

• Involved in growth of foetus before birth
• Probably no role in adult life

 

IGF receptors

IGF-I receptor is very similar to insulin receptor.

IGF-II receptor is a mannose-6-phosphate receptor.

 

Growth hormone regulation

Increased by

• exercise
• fasting, hypoglycemia
• protein meal
• stress
• glucagon
• going to sleep
• oestrogen and androgens

Decreased by

• REM sleep
• Glucose
• Cortisol
• FFA
• Growth hormone
• IGF-I
  * directly via negative feedback on pituitary
  * indirectly via stimulating somatostain secretion from hypothalamus

NB:

[WG21:408] ???? Growth hormone does not seem to feedback to hypothalamus directly

IGF-I feeds back on anterior pituitary to reduce GH secretion

BUT, table 22-4 does show GH as one of the inhibitors

Growth

Once pubertal growth spurt started, linear growth continues even if caloric intake reduced.

2 periods of rapid growth

1. in infancy
2. in late puberty

Growth promoted by

• growth hormone (include IGF-1)
• androgen and oestrogen
• thyroid hormone
  * permissive role only
  * does not induce growth by itself
  * effects ossification of cartilege, teeth growth, face contour, proportion of body

Other notes

Achondroplasia

Most common from of dwarfism

Autosomal dominant

 

Short stature

Can be due to deficiency of GRH, GH, IGF-I, and others

GH-related causes are mostly due to GRH deficiency