Normal growth and clinical aspects

Question 1

What happens in growth?

Answer 1

• GH is released from the anterior pituitary gland and promotes growth
• GH required permissive action of thyroid hormones and insulin
• IGF-1 is released from the liver (and other tissues) in response to GH released from the anterior pituitary
• IGF-1 controls GH through a negative feedback loop
○ It inhibits GHRH
○ It stimulates GHIH
• GH secretion is controlled by the hypothalamus which secretes GHRH and somatostatin
• Large quantities of GH are present in the pituitary of both adults and children and the rate of secretion increases and decreases in response to stimuli
• There is approximately a 20X increase in GH secretion in children during deep delta sleep
• Hypothalamic/ pituitary of GH/ IGF-1
○ Fluctuations in GHRH and coincident surges in GH occur spontaneously as well as in response to specific stimuli
○ SS secretion tends to be tonic (slow and responsive to need)
○ There is negative feedback control via long and short loops by GH and IGF-1
○ There are many inputs which stimulate hypothalamic control

Question 2

What stimuli increase GHRH secretion?

Answer 2

○ Actual or potential decrease in energy supply to cells
- GH needed for maintenance of tissues and their energy supply
- In fasting and hypoglycemia there is a decrease in substrate supply
- In exercise and the cold there is an increase demand for energy
- All stimuli increase GH
○ Increased amounts of amino acids in the plasma
- GH promotes amino acid transport and protein synthesis by muscle and liver
- Increases GH secretion
○ Stressful stimuli e.g. infection or psychological stress
○ Delta sleep
- Growth spurts in children
- Tissue repair in adults
○ Oestrogen and androgens (puberty)

Question 3

What are the stimuli that increases GHIH secretion?

Answer 3

○ Glucose
○ FFA (free fatty acid)
○ REM sleep
○ Cortisol (although inhibitory effect of growth may be to do with increased protein catabolism than stimulating GHIH release)

Question 4

What are the effects of growth hormone?

Answer 4

• Stimulation of cell size and cell division
• Maintenance of tissues
• Energy supply to tissues
• Bone growth
• Increases gluconeogenesis by the liver
• Reduces the ability to stimulate glucose uptake by muscle and adipose tissue
• Makes adipocytes more sensitive to lipolytic stimuli
• Increases muscle, liver and adipose tissue amino acid uptake and protein synthesis= anabolic effect (cortisol stimulates protein catabolism)
• Not needed for foetal growth or the growth of the first 8-10 months as it is controlled by nutritional intake

Question 5

What does somatotropin mean?

Answer 5

• AKA growth hormone (trop relates to growth)
○ GH is species specific
○ Is a peptide hormone
○ 50% bound to carrier proteins

Question 6

What does somatostatin mean?

Answer 6

•AKA Growth hormone inhibiting hormone (GHIH) (statin relating to stasis)
○ Neurohormone released from the hypothalamus
○ Inhibits the action of GH

Question 7

What does somatomedian mean?

Answer 7

• AKA IGF-1 (insulin-like growth factor-1)
○ Mediates the action of GH
○ Has a structure very similar to pro-insulin
○ Binds to receptors very similar to insulin
○ Hypoglycaemic qualities
○ Glucose uptake in muscles
○ Secreted by the liver
○ IGF-2 exists but is limited to the foetus and neonates

Question 8

explain bone growth

Answer 8

○ GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes
○ During the differentiating, the cells begin to secrete IGF-1 and to become responsive to IGF-1
○ IGF-1 then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation of bone growth
○ Epiphyseal plates close in adolescence under the influence of sex steroid hormones, then no further longitudinal growth is possible