Normal Growth and Clinical Aspects

Question 1

What are examples of some things that regulate growth?

Answer 1

Growth hormone release from anterior pituitary (which in turn is regulated by the balance of GHH vs GHIH from hypothalamus)

Thyroid hormones

Insulin

Sex steroids (especially at puberty)

Availability of nutrients

Stress

Genetics

Question 2

What is the classification of growth hormone?

Answer 2

Peptide hormone

Question 3

What is growth hormone (GH) also called?

Answer 3

Somatotropin

Question 4

What is growth hormone released from?

Answer 4

Anterior pituitary

Question 5

Growth hormone release is controlled via the release of two hypothalamic neurohormones with opposing actions, what are these?

Answer 5

Growth hormone inhibiting hormone (GHIH)

Growth hormone releasing hormone (GHRH)

Question 6

What is growth hormone inhibiting hormone also called?

Answer 6

Somatostatin

Question 7

What are the 2 broad categories that the actions of GH can be defined into?

Answer 7

Growth and development (indirect action)

Regulation of metabolism (direct action)

Question 8

What is the indirect action of GH?

Answer 8

Growth and development

Question 9

What is the direct action of GH?

Question 10

When does the main driver of growth change from nutritional intake to GH?

Answer 10

Growth in foetal period and first 8-10 months is largely controlled by nutritional intake

After this GH becomes dominant influence on rate at which children grow

Question 11

GH requires the permissive action of what before it will stimulate growth?

Answer 11

Thyroid hormones and insulin

Question 12

Why do children with untreated hypothyroidism of uncontrolled diabetes have stunted growth?

Answer 12

Because the permissive actions of thyroid hormones and insulin is required before GH will stimulate growth

Question 13

Why do GH secretions continue throughout adult life even once a child has grown to their full height?

Answer 13

It is essential in the maintenance and repair of tissue

Question 14

What do the growth promoting effects of GH stimulate on its target tissues?

Answer 14

Stimulate both cell size (hypertrophy) and cell division (hyperplasia)

Question 15

How is the effect of GH on growth indirect?

Answer 15

Achieved through its action of an intermediate (insulin like growth factor-1, or IGF-1)

Question 16

What does IGF-1 stand for?

Answer 16

Insulin like growth factor 1

Question 17

What is insulin like growth factor-1 (IGF-1) also called?

Answer 17

Somatomedian C

Question 18

Why is IGF-1 named as it is?

Answer 18

Similar structure to proinsulin, binds to receptors similar to insulin receptor and has hypoglycaemic qualities

Question 19

Where are IGF-1 receptors found?

Answer 19

Muscle has many

Fat and liver have few

Question 20

What is IGF-1 secreted by and in response to?

Answer 20

By the liver in response to GH release

Question 21

How does IGF-1 control GH release?

Answer 21

Through a negative feedback loop

Question 22

As well as IGF-1, IGF-2 exists. What is its functional importance?

Answer 22

Limited to the foetus and neonate

Question 23

How are GH and IGF-1 transported around the blood?

Answer 23

Although they are peptide hormones, they are transported in the blood bound to carrier proteins (50% of GH is in this form)

Question 24

What percentage of GH in the blood is bound to carrier proteins?

Answer 24

50%

Question 25

What are advantages of GH and IGF-1 being transported in blood bound to proteins?

Answer 25

Helps to provide a reservoir of GH in the blood to smooth out the effects of the erratic pattern of secretion Extends the half life by protecting from excretion

Question 26

How does IGF exhibit negative feedback on GH release?

Answer 26

By both inhibiting GHRH and stimulating GHIH

Question 27

As well as IGF, what else provides a negative feedback loop for GH release?

Answer 27

Somatotrophs in pituitary

Question 28

Explain the process of GH/IGF-1 having an effect on bone growth?

Answer 28

1) GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes 2) During the differentiation the cells begin to secrete IGF-1 and to become responsive to IGF-1 3) 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 29

What are the precursors of chondrocytes called?

Answer 29

Prechondrocytes

Question 30

When and why do epithyseal plates close?

Answer 30

During adolescence under the influence of sex steroids so no further longitudinal growth is possible

Question 31

What are some examples of the effects that GH has on metabolism?

Answer 31

Increases gluconeogenesis by liver Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue Makes adipocytes more sensitive to lipolytic stimuli Increases amino acid uptake and protein synthesis in almost all cells (anabolic effect)

Question 32

Does GH have a pro or anti-insulin effect?

Answer 32

Anti-insulin effects, synergising with cortisol in this respect So it is said to be diabetogenic (increases blood glucose)

Question 33

What effect does insulin and GH have on amino acid uptake?

Answer 33

Both increase amino acid uptake

Question 34

What effect does insulin and GH have on protein synthesis?

Answer 34

Both increase protein synthesis

Question 35

What effect does insulin and GH have on glucose uptake?

Answer 35

Insulin increases glucose uptake whereas GH does not

Question 36

How does GH impact glucose metabolism?

Answer 36

Mobilises glucose stores to increase blood [glucose] Inhibits action of insulin (by reducing number of insulin receptors on muscle and adipose tissue) thus augmenting the increased blood [glucose] Promotes lipolysis, providing a source of energy for most cells of body sparing glucose and again augmenting increased blood [glucose] Promotes amino acid uptake into cells to support protein synthesis

Question 37

When does the highest rate of GH secretion occur?

Answer 37

During teenage years

Question 38

During sleep, when is the majority of GH released?

Answer 38

During the first 2 hours of sleep (deep delta sleep)

Question 39

Is GH release greater during waking or sleeping hours?

Answer 39

Sleeping hours, it is low during waking hours

Question 40

Despite GH spikes, plasma levels of IGF-1 remains relatively constant, what does this suggest?

Answer 40

IGF-1 buffers the pulsatile variance in GH levels

Question 41

What are examples of stimuli that increases GHRH secretion (causing increased GH)?

Answer 41

Actual or potential decrease in energy supply to cells Increased amount of amino acids in plasma Stressful stimuli Delta sleep Oestrogen and testosterone

Question 42

Why does increased amounts of amino acid in the plasma increase the amount of GH secretion?

Answer 42

GH promotes amino acid transport and protein synthesis by muscle and liver

Question 43

What are examples of stressful stimulis that can increase GH secretion?

Answer 43

Infection or psychological stress

Question 44

How does oestrogen and testosterone effact the secretion of GH?

Answer 44

Stimulates GH release from pituitary directly as well as decreasing IGF mediated negative feedback Responsible for growth spurt in puberty

Question 45

What are examples of stimuli that increases GHIH (causing decreased GH)?

Answer 45

Glucose Free fatty acids REM sleep Cortisol

Question 46

Why does cortisol have an inhibitory effect on growth?

Answer 46

Increase GHIH secretion Increased protein catabolism

Question 47

What are the 3 factors that affects the physiology of growth?

Answer 47

Hormones Nutrition Genetics

Question 48

What are some examples of hormones that impact growth?

Answer 48

GH IGF-1 Thyroid hormones Sex steroids Glucocorticoids Insulin

Question 49

What hormone dominates growth throughout your life?

Answer 49

None, different hormones dominate growth during different periods of growth

Question 50

When do the sex hormones start to dominate growth?

Answer 50

Minor influence until puberty when they dominate growth spurt

Question 51

When does GH not really impact growth?

Answer 51

Minor influence in foetal life (believed insulin and IGF-II dominate growth at that time)

Question 52

Thyroid hormons are essential for normal growth, particularly when?

Answer 52

During development of the nervous system in ureto and early childhood

Question 53

Are thyroid hormones permissive or antagonistic to GH/IGF-I?

Answer 53

Permissive

Question 54

What effects do thyroid hormones have that means they contribute to growth in early childhood?

Answer 54

Widespread effects on ossification of cartilage and teeth maturation as well as the contours of the face and proportions of the body

Question 55

In terms of nutrition, what is important for growth?

Answer 55

Protein content and essential vitamins and minerals as well as enough calories

Question 56

Why does injury and disease stunt growth in childhood?

Answer 56

Injury and disease stunt growth because increase protein catabolism (glucocorticoid effects)

Question 57

In humans there are 2 periods of rapid growth, what are these?

Answer 57

Infancy Puberty

Question 58

Why does the rapid growth period during puberty occur?

Answer 58

Due to androgens and oestrogens, produce spikes in GH secretion that increases IGF-1 which increases growth Same sex hormones terminate growth by causing the epiphyses of the long bones to fuse

Question 59

How do the effects of GH/IGF-1 contrast at the start of puberty and at the end?

Answer 59

Start - promote bone elongation and increased height, weight and body masss End - close epithyses plates and stop bone elongation

Question 60

What do endocrine tumours usually cause?

Answer 60

Gigantism Acromegaly