Normal Growth and Clinical Aspects Flashcards
What are examples of some things that regulate growth?
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
What is the classification of growth hormone?
Peptide hormone
What is growth hormone (GH) also called?
Somatotropin
What is growth hormone released from?
Anterior pituitary
Growth hormone release is controlled via the release of two hypothalamic neurohormones with opposing actions, what are these?
Growth hormone inhibiting hormone (GHIH)
Growth hormone releasing hormone (GHRH)
What is growth hormone inhibiting hormone also called?
Somatostatin
What are the 2 broad categories that the actions of GH can be defined into?
Growth and development (indirect action)
Regulation of metabolism (direct action)
What is the indirect action of GH?
Growth and development
What is the direct action of GH?
regulation of metabolism
When does the main driver of growth change from nutritional intake to GH?
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
GH requires the permissive action of what before it will stimulate growth?
Thyroid hormones and insulin
Why do children with untreated hypothyroidism of uncontrolled diabetes have stunted growth?
Because the permissive actions of thyroid hormones and insulin is required before GH will stimulate growth
Why do GH secretions continue throughout adult life even once a child has grown to their full height?
It is essential in the maintenance and repair of tissue
What do the growth promoting effects of GH stimulate on its target tissues?
Stimulate both cell size (hypertrophy) and cell division (hyperplasia)
How is the effect of GH on growth indirect?
Achieved through its action of an intermediate (insulin like growth factor-1, or IGF-1)
What does IGF-1 stand for?
Insulin like growth factor 1
What is insulin like growth factor-1 (IGF-1) also called?
Somatomedian C
Why is IGF-1 named as it is?
Similar structure to proinsulin, binds to receptors similar to insulin receptor and has hypoglycaemic qualities
Where are IGF-1 receptors found?
Muscle has many
Fat and liver have few
What is IGF-1 secreted by and in response to?
By the liver in response to GH release
How does IGF-1 control GH release?
Through a negative feedback loop
As well as IGF-1, IGF-2 exists. What is its functional importance?
Limited to the foetus and neonate
How are GH and IGF-1 transported around the blood?
Although they are peptide hormones, they are transported in the blood bound to carrier proteins (50% of GH is in this form)
What percentage of GH in the blood is bound to carrier proteins?
50%
What are advantages of GH and IGF-1 being transported in blood bound to proteins?
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
How does IGF exhibit negative feedback on GH release?
By both inhibiting GHRH and stimulating GHIH
As well as IGF, what else provides a negative feedback loop for GH release?
Somatotrophs in pituitary
Explain the process of GH/IGF-1 having an effect on bone growth?
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
What are the precursors of chondrocytes called?
Prechondrocytes
When and why do epithyseal plates close?
During adolescence under the influence of sex steroids so no further longitudinal growth is possible
What are some examples of the effects that GH has on metabolism?
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)
Does GH have a pro or anti-insulin effect?
Anti-insulin effects, synergising with cortisol in this respect
So it is said to be diabetogenic (increases blood glucose)
What effect does insulin and GH have on amino acid uptake?
Both increase amino acid uptake
What effect does insulin and GH have on protein synthesis?
Both increase protein synthesis
What effect does insulin and GH have on glucose uptake?
Insulin increases glucose uptake whereas GH does not
How does GH impact glucose metabolism?
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
When does the highest rate of GH secretion occur?
During teenage years
During sleep, when is the majority of GH released?
During the first 2 hours of sleep (deep delta sleep)
Is GH release greater during waking or sleeping hours?
Sleeping hours, it is low during waking hours
Despite GH spikes, plasma levels of IGF-1 remains relatively constant, what does this suggest?
IGF-1 buffers the pulsatile variance in GH levels
What are examples of stimuli that increases GHRH secretion (causing increased GH)?
Actual or potential decrease in energy supply to cells
Increased amount of amino acids in plasma
Stressful stimuli
Delta sleep
Oestrogen and testosterone
Why does increased amounts of amino acid in the plasma increase the amount of GH secretion?
GH promotes amino acid transport and protein synthesis by muscle and liver
What are examples of stressful stimulis that can increase GH secretion?
Infection or psychological stress
How does oestrogen and testosterone effact the secretion of GH?
Stimulates GH release from pituitary directly as well as decreasing IGF mediated negative feedback
Responsible for growth spurt in puberty
What are examples of stimuli that increases GHIH (causing decreased GH)?
Glucose
Free fatty acids
REM sleep
Cortisol
Why does cortisol have an inhibitory effect on growth?
Increase GHIH secretion
Increased protein catabolism
What are the 3 factors that affects the physiology of growth?
Hormones
Nutrition
Genetics
What are some examples of hormones that impact growth?
GH
IGF-1
Thyroid hormones
Sex steroids
Glucocorticoids
Insulin
What hormone dominates growth throughout your life?
None, different hormones dominate growth during different periods of growth
When do the sex hormones start to dominate growth?
Minor influence until puberty when they dominate growth spurt
When does GH not really impact growth?
Minor influence in foetal life (believed insulin and IGF-II dominate growth at that time)
Thyroid hormons are essential for normal growth, particularly when?
During development of the nervous system in ureto and early childhood
Are thyroid hormones permissive or antagonistic to GH/IGF-I?
Permissive
What effects do thyroid hormones have that means they contribute to growth in early childhood?
Widespread effects on ossification of cartilage and teeth maturation as well as the contours of the face and proportions of the body
In terms of nutrition, what is important for growth?
Protein content and essential vitamins and minerals as well as enough calories
Why does injury and disease stunt growth in childhood?
Injury and disease stunt growth because increase protein catabolism (glucocorticoid effects)
In humans there are 2 periods of rapid growth, what are these?
Infancy
Puberty
Why does the rapid growth period during puberty occur?
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
How do the effects of GH/IGF-1 contrast at the start of puberty and at the end?
Start - promote bone elongation and increased height, weight and body masss
End - close epithyses plates and stop bone elongation
What do endocrine tumours usually cause?
Gigantism
Acromegaly
