Lecture 4: Endocrine Control of Growth and Disorders of Growth

Question 1

list the hormones involved with growth

Answer 1

1. growth hormone (& GHRH VS GHIH)
2. IGF-1
3. thyroid hormones
4. insulin
5. sex steroids (particularly at puberty)
6. cortisol (antagonistic)

Question 2

describe the infancy growth period

Answer 2

• period of rapid growth
• growth in the foetal period and the first 8-10 months of life is largely controlled by nutritional intake, thyroid hormones and insulin.
• growth hormone becomes significant from around 10 months.

Question 3

describe growth in relation to puberty

Answer 3

• period of rapid growth
• due to androgens and oestrogens > produce spikes in GH secretion that increase IGF-1 and stimulate growth.

Question 4

what is the role of GH/IGF-1 during normal puberty?

Answer 4

• before the epiphyseal plates fuse, GH/IGF-1 promote bone elongation and increased height, weight and body mass.

Question 5

what is the role of sex hormones in the later stages of puberty?

Answer 5

act to close the epiphyses and hence stop bone elongation

Question 6

which hormones dominate intra-uterine growth?

Answer 6

thyroid hormones, insulin and IGF-II

Question 7

what is congenital hypothyroidism and what is its consequence on growth?

Answer 7

• a condition where babies are born of normal size but are unable to produce their own thyroid hormone.
• if left untreated, they have retarded growth and development > they retain infantile facial features.

Question 8

what can maternal iodine deficiency during pregnancy cause?

Answer 8

may result in severely retarded intra-uterine growth

Question 9

thyroid hormone has a permissive effect on?

Answer 9

growth hormone > loss of permissive effect severely impacts on GH action

Question 10

what is another name for growth hormone released from the anterior pituitary?

Answer 10

somatotropin (released from somatotroph cells)

Question 11

the release of growth hormone is controlled via the release of which two hypothalamic neurohormes?

Answer 11

GHIH (somatostatin) and GHRH

Question 12

before stimulating growth, GH requires permissive action from which hormones?

Answer 12

thyroid hormones and insulin
> Children with untreated hypothyroidism, or poorly controlled diabetes, have stunted growth despite normal GH levels.

Question 13

what does GH promote at the cellular level?

Answer 13

• an increase in both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues

Question 14

what receptors does growth hormone bind to?

Answer 14

• tyrosine kinase receptors > results in phosphorylation of intracellular targets > downstream effects

Question 15

what are the two main actions of growth hormone?

Answer 15

• growth of long bones (indirect action mediated via IGF-I)
• regulation of metabolism (direct action)

Question 16

what is another name for IGF-1?

Answer 16

somatomedin C

Question 17

function of IGF-I

Answer 17

has ‘insulin-like’ qualities in that it stimulates glucose uptake in muscle, and in bone

Question 18

IGF-I secretion

Answer 18

• IGF-I is secreted primarily by the liver in response to GH release, and IGF-I controls GH release through a negative feedback loop.

Question 19

how are GH and IGF-I transported through the blood?

Answer 19

bound to carrier proteins

Question 20

how does GH regulate metabolism?

Answer 20

1. increases gluconeogenesis by the liver
2. reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue
3. makes adipocytes more sensitive to lipolytic stimuli
4. increases amino acid uptake and protein synthesis in almost all cells = anabolic effect (cortisol stimulates protein catabolism)

Question 21

why is GH said to be diabetogenic?

Answer 21

it increases blood glucose in excess by inhibiting the action of insulin

Question 22

what phase of sleep is GH release at its highest?

Answer 22

• released during first 2 hours of sleep (deep delta sleep).

Question 23

why is the half life of IGF-I 20 hours whereas GH is 20 mins?

Answer 23

• IGF-I binds much more tightly to carrier proteins than GH so is less vulnerbale to degradation

Question 24

list the stimuli that increase GHRH secretion (and therefore GH secretion)

Answer 24

1. actual or potential decrease in energy supply to cells e.g. fasting, hypoglycaemia, exercise, cold.
2. increased amounts of amino acids in the plasma e.g. protein meal
3. physical stress and illness (although growth may actually be stunted due to catabolic action of cortisol)
4. delta-sleep
5. oestrogen and testosterone

Question 25

list the stimuli that increase GHIH (somatostatin) secretion, and therefore decrease growth hormone secretion

Answer 25

1. glucose
2. FFA
3. ageing
4. cortisol (although inhibitory effect on growth may be more to do with increased protein catabolism than stimulating GHIH release)

Question 26

describe gigantism

Answer 26

• excess growth hormone due to pituitary tumour before epiphyseal plates of long bones close
• causes excessive growth, may be more than 7ft (210cm) tall

Question 27

describe acromegaly

Answer 27

• excess growth hormone due to a pituitary tumour after epiphyseal plates have sealed.
• grow outwards rather than upwards, characteristic features are enlarged hands and feet and facial features.

Question 28

what is the treatment for gigantism or acromegaly?

Answer 28

surgery to remove tumour
somatostatin analogues

Question 29

list the causes of an unusually small stature

Answer 29

• GHRH deficiency
• GH deficiency
• genetic mutation or under expression of GH receptor
• precocious (early) puberty > early sex hormone release
• hypothyroid dwarfism

Question 30

list the glucose counter regulatory hormones

Answer 30

• cortisol
• epinephrine
• glucagon
• growth hormone

released in response to decreased concentration of blood glucose