Normal growth + clinical aspects

Question 1

Growth is regulated by what different factors (7)

Answer 1

Growth hormone (from AP)
Thyroid hormones
Insulin
Sex steroids (mainly at puberty)
Nutrient availability
Stress
Genetics

Question 2

Growth hormone release is regulated by the balance of what 2 other hormones from the hypothalamus

Answer 2

GHRH

GHIH aka somatostatin

Question 3

Growth hormone aka

+ secreted by

Answer 3

somatotropin

AP

Question 4

Growth hormone has a DIRECT and INDIRECT action

• what does the indirect action do
• what does the direct action do

Answer 4

Indirect action - involved in growth and development

Direct action - regulates metabolism

Question 5

Growth in the foetal period and 10 months of life is largely dependent on what

Answer 5

nutritional intake (NOT GROWTH HORMONE)

Question 6

After what age does growth hormone become the dominant influence of growth

Answer 6

After 10 months

Question 7

GH requires the PERMISSIVE action of what other things before it can stimulate growth, without these GH itself stunts growth

Answer 7

Thyroid hormones

Insulin

Question 8

GH secretion continues throughout adult life - why?

Answer 8

essential in maintenance and repair of tissue

Question 9

How does GH stimulate growth (2)

Answer 9

Stimulates hypertrophy + hyperplasia (cell division) in its target tissues

Question 10

Growth hormone has a DIRECT and INDIRECT action:

Indirect action:

Describe how GH indirectly promotes growth + development (3)
-mention what intermediate is involved

Answer 10

Involves the intermediate, insulin-like growth factor-1 (IGF-1) aka somatomedin C

GH stimulates chondrocyte precursor cells in epiphyseal plates to differentiate into chondrocytes

During differentiation, the chondrocytes begin to secrete IGF-1 and become responsive to IGF-1

IGF-1 then acts as an autocrine/paracrine agent to stimulate the differentiating chondrocytes to undergo cell division + produce cartilage –> calcifies into bone

Question 11

Insulin-like growth factor-1 (IGF-1) has a structure similar to what + what tissue does it have most effect on

Answer 11

Pro-insulin

Mostly causes glucose uptake in muscle as liver and adipose tissue have few IGF receptors

Question 12

IGF-1 is secreted by what organ in response to GH release

Answer 12

Liver

Question 13

How does IGF-1 control GH release

Answer 13

Via a negative feedback loop

-presence of IGF-1 feedbacks to the hypothalamus to inhibit GHRH and stimulate GHIH

Question 14

Does GH travel freely in the blood

Answer 14

50% is bound to protein to provide a reservoir of GH

Question 15

Somatostatin aka

+ secreted by

Answer 15

GHIH

hypothalamus

Question 16

Somatomedin C aka

Answer 16

Insulin-like growth factor-1 (IGF-1)

-mediates GH

Question 17

Apart from IGF-1 exhibiting negative feedback on GH release, what else exhibits negative feedback on GH release

Answer 17

GH itself has a negative feedback loop on its own release from somatotropin in the pituitary gland

Question 18

What stimulates epiphyseal plates to close during adolescence (i.e. no further longitudinal growth)

Answer 18

Sex steroids - stimulate apoptosis of chondrocytes

Question 19

Growth hormone has a DIRECT and INDIRECT action:

DIRECT action:

Describe 4 mechanisms that GH DIRECTLY regulates metabolism

Answer 19

1. Increases gluconeogenesis by the liver.
2. Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
3. Promotes lipolysis to provide additional energy
4. Increases amino acid uptake and protein synthesis in almost all cells = ANABOLIC effect

Question 20

Growth hormone DIRECTLY regulates metabolism via 4 mechanisms:

1. Increases gluconeogenesis by the liver.
2. Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
3. Promotes lipolysis to provide energy source
4. Increases amino acid uptake and protein synthesis in almost all cells = ANABOLIC effect

What is common about the first 3 mechanisms?

What’s different about the 4th mechanism?

Answer 20

In all of these actions GH is releasing energy stores to support growth.

It is having an “anti-insulin” effect and synergises with CORTISOL in this respect.

GH is therefore said to be diabetogenic (increases blood glucose) when present in excess

4th mechanism - GH acts unlike cortisol and just like insulin

Question 21

Are insulin and GH catabolic or anabolic hormones

Answer 21

anabolic

Question 22

What does insulin stimulate that GH doesn’t

Answer 22

glucose uptake

Question 23

Highest rates of secretion of GH occur during what years of life

Answer 23

teen

Question 24

Secretion rate of GH undergoes rapid spontaneous fluctuations over 24 hours, however plasma levels of IGF-1 remain quite constant which suggests what

Answer 24

IGF-1 buffers the pulsatile variance in GH levels

Question 25

As well as IGF-1 and GH itself controlling the release of GH, what else is GH secretion influenced by

Answer 25

Nutritional status | -mediates GH release via control of GHRH/GHIH release from hypothalamus

Question 26

Stimuli that increase GHRH secretion (therefore increasing GH secretion)

Answer 26

1. Decrease in energy supply to cells 2. Increased plasma amino acids 3. Stressful stimuli, e.g. infection, psychological stress 4. Delta sleep 5. Oestrogen and testosterone

Question 27

How does decreased energy supply to cells stimulate GHRH secretion thus increasing GH secretion

Answer 27

GH is also needed for maintenance of tissues and their energy supply, so in situations where more energy is needed like fasting, exercise, cold weather, energy demand is increased which stimulates GH secretion

Question 28

How does a rise in the plasma amino acid level after the digestion and absorption of a large protein meal affect GH secretion

Answer 28

Would stimulate an increase in GHRH secretion thus increasing GH secretion as GH promotes amino acid transport and protein synthesis by muscle and lover

Question 29

Stimuli that increase GHIH secretion (thus decreasing GH secretion) (4)

Answer 29

Glucose Free fatty acids REM sleep Cortisol

Question 30

3 factors affecting growth

Answer 30

Hormones Nutrition Genetics

Question 31

Name 6 hormones that affect growth

Answer 31

``` GH Insulin-like growth factor-1 (IGF-1) Thyroid hormones Sex steroids Glucocorticoids Insulin ```

Question 32

What 2 hormones are associated with intrauterine growth

Answer 32

Insulin IGF-II

Question 33

What stages of life are thyroid hormones particularly important (2)

Answer 33

In utero - for development of nervous system Early childhood

Question 34

What is cretinism

Answer 34

Condition where children are hypothyroid from birth. They have retarded growth because of the loss of thyroid hormone's permissive action on GH GH LEVELS ARE NORMAL

Question 35

2 periods of rapid growth occur in humans - when are they

Answer 35

Infancy Puberty

Question 36

Hypersecretion of GH is usually due to what pathology

Answer 36

Endocrine tumours

Question 37

What is gigantism

Answer 37

Excess GH due to a pituitary tumour BEFORE epiphyseal plates of long bones close --> excessive growth

Question 38

What is acromegaly

Answer 38

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 but non-long bones can still grow so can get big hands and feet

Question 39

Classic sign of acromegaly

Answer 39

Large feet

Question 40

Treatment of acromegaly (2)

Answer 40

Removal of tumour or somatostatin analogue

Question 41

Features of hypothyroid children v GH deficient children

Answer 41

Hypothyroid - retain infantile proportions (i.e. still look like an infant) GH deficient - proportionally normal, just small/short