Normal growth and clinical aspects

Question 1

Where is growth hormone released from?

Answer 1

Anterior pituitary

Question 2

What is another name for growth hormone?

Answer 2

Somatotrophin

do not confuse with somatostatin/GH inhibiting hormone

Question 3

What type of hormone is growth hormone/somatothrophin?

Answer 3

Classic endocrine peptide hormone

Question 4

What type of hormone is somatostatin/GHIH?

Answer 4

Neurohormone

Question 5

Where is somatostatin/GHIH released from?

Answer 5

Hypothalamus

Question 6

What hormones elicit a permissive effect for GH to stimulate growth?

Answer 6

Thyroid hormones

Insulin

Question 7

What influences growth in the foetal period and the first 8-10 months of life?

Answer 7

Nutritional intake

Question 8

What is the other name for insulin-like growth factor 1 (IGF-1)?

Answer 8

somatomedian

Question 9

What mediates GHs effects on cell division?

Answer 9

IGF-1/somatomedian

Question 10

What is IGF-1 similar to in structure?

Answer 10

Proinsulin

Question 11

How is IGF-1 found to have hypoglycaemic qualities?

Answer 11

Causes glucose uptake in muscle cells, though not in liver and adipose tissue as they have few IGF receptors

Question 12

What is the main tissue that secretes IGF-1?

Answer 12

Liver

Question 13

What is IGF-II involved in?

Answer 13

Growth during foetal period and in neonate

Question 14

What acts as a negative feedback signal for GH release?

Answer 14

IGF

GH itself

Question 15

How does IGF act as a negative feedback signal for GH release?

Answer 15

IGF exhibits negative feedback on GH release both via inhibiting GHRH and stimulating GHIH/somatostatin.

Question 16

What are the effects of GH and IGF on bones?

Answer 16

• GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes.
• During the differentiation, the cells begin to secrete IGF-I and to become responsive to IGF-I
• IGF-I than 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 17

What causes epiphyseal plates to close?

Answer 17

Sex steroid hormones during pregnancy

Question 18

What are the direct effects of GH on the liver, muscle and adipose tissue?

Answer 18

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 muscle, liver and adipose tissue amino acid uptake and protein synthesis

Question 19

What is basal [GH] in plasma in kids and adults?

Answer 19

0-3ng/ml

Question 20

What is the 24-hour mean [GH] in both adults and in children/puberty?

Answer 20

2-4ng/ml in adults

5-8ng/ml in children and those going through puberty

Question 21

By how much does GH secretion increase during sleep in children?

Answer 21

Approximately 20X ↑ in GH secretion in children during stages of deep delta sleep. General energy requirements low so energy diverted to growth.

Question 22

About what % of GH is bound in plasma (even though it is a peptide hormone)?

Answer 22

50%

Question 23

Why is GH and IGF unusual for peptide hormones?

Answer 23

Transported in blood with binding proteins

Question 24

What is the physiological significance of bound GH in the blood?

Answer 24

May help prevent too much fluctuation in GH concentration in the blood

Question 25

What stimulates an increase in GRHR secretion to induce GH secretion?

Answer 25

``` Actual/potential decrease in energy supply for cells Increased amino acids in blood Stress Delta sleep Oestrogen and androgens ```

Question 26

What stimulates an increase in GRIR secretion to reduce GH secretion?

Answer 26

Glucose Free fatty acids REM sleep Cortisol

Question 27

What 3 factors influence growth?

Answer 27

o Hormones o Nutrition o Genetics

Question 28

List the hormones involved in growth

Answer 28

``` o GH o IGF-I o Thyroid hormones o Androgens o Oestrogens o Glucocorticoids o Insulin ```

Question 29

What hormones dominate intrauterine growth?

Answer 29

Insulin | IGF-II

Question 30

Why are babies born with GH deficiency not born small?

Answer 30

Insulin and IGF-II dominate early growth | GH kicks in during childhood

Question 31

What are some of the functions of thyroid hormones in growth?

Answer 31

Nervous system development in utero Ossification of cartilage Teeth maturation Contours of face/body proportions

Question 32

What causes cretinism?

Answer 32

Cretinism is a condition where children are hypothyroid from birth. They have retarded growth because of the loss of TH’s permissive action on GH. They retain infantile facial features = hypothyroid dwarf. GH levels are normal e.g. hypothyroid tadpoles never become frogs

Question 33

What are the two rapid periods of growth in humans?

Answer 33

Infancy e.g. 2.5cm a day | Puberty

Question 34

What causes growth in puberty, and how do hormones also influence the termination of growth?

Answer 34

Puberty: due to androgens and oestrogens, produce spikes in GH secretion that ↑ IGF-I →↑ growth. The same hormones also terminate growth by causing the epiphyses of the long bones to fuse. So, in normal puberty, before the epiphyseal plates fuse, GH/IGF-I promote bone elongation and increased height, weight and body mass. Sex hormones in the later stages of puberty act to close the epiphyses and hence stop bone elongation.

Question 35

What hormones in the later stages of puberty cause the closure of the epiphyses to stop bone elongation?

Answer 35

Sex hormones

Question 36

What is the difference between hypersecretion of GH in gigantism and acromegaly?

Answer 36

* Gigantism: excess GH due to a pituitary tumour before epiphyseal plates of long bones close→ excessive growth, may be more than 7ft tall (210cm), called pituitary giants. * Acromegaly: excess GH due to a pituitary tumour after epiphyseal plates have sealed. Long bones cannot increase so there is no longitudinal growth and no increase in height. However, can still grow in other directions and the characteristic features are enlarged hands and feet.

Question 37

Whats the classic sign of acromegaly?

Answer 37

Feet keep growing

Question 38

How is hypersecretion of GH caused by, and how is it treated?

Answer 38

Caused by excess GH due to a pituitary tumour Surgery or somatostatin analogues

Question 39

What can cause dwarfism?

Answer 39

``` GHRH deficiency Abnormal GH cell secretion End organ is irresponsive to GH (Laron dwarfism) Genetic mutations e.g. pygmies Precocious puberty Achondroplasia ```

Question 40

Describe Larons dwarfism

Answer 40

End organ is unresponsive to GH (Laron Dwarfism) - Individuals may have ↑ [GH] in plasma. Defect GH receptor prevents IGF-1 release and peripheral tissues cannot respond to growth signal. Loss of IGF-1 inhibition of GH responsible for ↑ [GH] (remember negative feedback loop!).

Question 41

What genetic mutation is seen in pygmies?

Answer 41

Pygmies have a genetic mutation that impairs the ability of cells to produce IGF-I in response to GH

Question 42

What causes achondroplasia?

Answer 42

Achondroplasia is caused by a mutation in fibroblast growth factor (FGF) receptor

Question 43

How does precocious puberty result in dwarfism?

Answer 43

Precocious puberty - excess GnRH release stimulates puberty via promoting sex hormone release. These children have stunted growth because long bones fuse early under influence of sex hormones.