Normal Growth and Clinical Aspects

Question 1

From where is GH released?

Answer 1

Anterior pituitary

Question 2

What is another name for GH?

Answer 2

Somatotrophin

Question 3

What type of hormone is GH?

Answer 3

Peptide hormone

Question 4

What is the growth factor which allows GH to achieve its effects on cell division?

Answer 4

IGF-1 Insulin-like growth factor-1

Question 5

What organs secrets IGF-1?

Answer 5

The liver

Question 6

What effects do GH/IGL-1 have on bone?

Answer 6

GH stimulates chondrocyte precursor cells in the epiphyseal plates to differentiate into chondrocytes
During the differentiation the cells begin to secrete IGF-1 and 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 for bone growth

Question 7

What causes the growth of epiphyseal plates and when?

Answer 7

The influence of sex hormones during adolescence

Question 8

What are four direct effects of GH?

Answer 8

1. Increases gluconeogenesis in the liver
2. Reduces the ability of insulin to simulate glucose uptake by muscle and fat cells
3. Made adipocytes more sensitive to lipolytic stimuli

These all have the effect of releasing glucose from stores in order to support growth - “anti-insulin effect’ and synergises with cortisol - said to be diabetogenic = increases BG

However, unlike cortisol and like insulin;

4. Increases muscle, liver and adipose tissue amino acid uptake and protein synthesis

Question 9

What controls GH secretion? How?

Answer 9

The hypothalamus via secretion of GHRH and SS

Question 10

What is the normal plasma range for basal GH in adults and children?

Answer 10

0-3ng/ml

24 hour monitoring required for accurate picture

Question 11

What is the change in GH in children during sleep?

Answer 11

20x increase in GH in children during delta sleep

Question 12

How do the rates of fluctuation over 24 hour periods vary from GH to IGF-1? What does this suggest?

Answer 12

GH peaks and troughs significantly throughout the day, but IGF-1 stays relatively constant, suggesting that it buffers the changes in GH

Question 13

How are GH and IGF-1 transported in the blood? Why is this strange?

Answer 13

With binding proteins (around 50% of GH is bound form)

Because both are peptide hormones and it is usually steroid and thyroid hormones which require protein bound transport

Question 14

What stimuli increase GHRH secretion? Why?

Answer 14

1. Actual or potential decrease in energy supply to cells - as well as growth and development GH is needed for maintenance of tissues and their energy supplies. In fasting and hypoglycaemia there is a decrease in substrate supply, in exercise and the cold there is an increased demand for energy - all of these stimulate GH release
2. Increased amounts of amino acids in the plasma e.g. protein meal - GH promotes amino acid transport and protein synthesis by muscle and liver
3. Stressful stimuli e.g. infection, physiological stress
4. Delta sleep - increase in GH in delta sleep in children and adolescents to promote growth and tissue repair
5. Oestrogen and androgens

Question 15

What stimuli decrease GH secretion?

Answer 15

1. Glucose
2. Cortisol
3. FFA
4. REM sleep (subjects deprived of REM sleep have increased GH secretion

Question 16

What three broad factors influence the physiology of growth?

Answer 16

Hormones
Nutrition
Genetics

Question 17

Give some hormones which influence the physiology of growth

Answer 17

GH, IGF-1, thyroid hormones, androgens, oestrogen, glucocorticoids and insulin

Question 18

What is the relevance of thyroid hormone in relation to GH/IGF-1?

Answer 18

Thyroid hormone is permissive to GH and IGF-1 - i.e. sensitises cells to them and increases their effectiveness

Question 19

What are the two periods of paid growth in humans? Describe them

Answer 19

Infancy - episodic- huge spurts and then nothing

Puberty - androgens and oestrogens spike GH -> spike IGF-1 -> spike growth. The same hormones then terminate growth by causing epiphyses of the long bones to fuse

Question 20

What is gigantism?

Answer 20

Excess GH due to a pituitary tumour BEFORE the epiphyseal plates of the long bones close

Question 21

What is acromegaly?

Answer 21

Excess GH due to a pituitary tumour AFTER the epiphyseal plates of long bones have closed, the bones cannot increase in length as the plates are closed so they instead grow in other directions and cause the classic features large hands and feet although there is no difference in overall height

Question 22

Give five causes for dwarfism

Answer 22

1. A deficiency of GHRH
2. Abnormal GH secreting cells
3. End organ unresponsive to GH (Laron Dwarfism)
4. Genetic mutations
5. Precocious puberty - early bone fusing under excess influence of sex hormones after premature GnRH release that stimulates puberty