Normal Growth and Clinical Aspects Flashcards
If u can, name 7 factors by which growth is regulated?
- growth hormone release form AP
- thyroid hormones
- insulin
- sex steroids
- availability of nutrients
- stress
- genetics
What type of hormone is growth hormone?
Peptide
Where is growth hormone (GH) released from?
Anterior pituitary
What is another name for growth hormone?
Somatotrophin
GH release is controlled via the release of which 2 hypothalamic neurohormones with opposing action?
Growth Hormone Inhibiting Hormone (GHIH)
Growth Hormone Releasing Hormone (GHRH)
What is another name for GHIH?
Somatostatin (opposite of somatotrophin)
What are the 2 broad categories of the action of growth hormone?
- Growth and development (indirect)
2. Regulation of metabolism (direct)
At what age does GH become the dominant influence on the rate at which children grow?
After 8-10 months 9 (before this it is largely nutrition)
What does GH require the permissive action of in order to stimulate growth?
Thyroid hormones and insulin
Growth-promoting effect of GH is mediated through stimulation of what in cells of its target tissues?
Hypertrophy
Hyperplasia
How is GH action indirect?
It is acheived through action of an intermediate known as insulin-like growth factor (IGF-1)
What is IGF-1 also known as?
Somatomedin C (MEDIates action of GH)
Why is IGF-1 ‘insulin-like’?
Binds to receptors v similar to insulin (tyrosine) receptor
Has hypoglycaemic qualities
What is the limitation to the hypoglycaemic quality of IGF-1?
Limited to glucose uptake in muscle (liver + adipose have few IGF receptors)
What stimulates the secretion of IGF-1 from the liver?
GH release
How does IGF-1 then control the release of GH?
Negative feedback loop
(not important) does IGF-II exist? what is its function?
yes; limited to foetus + neonate
What type of hormones are GH and IGF-1? What type of hormones do they behave like transport-wise?
Peptide
Behave like steroid/thyroid hormones - transported in blood bound to carrier proteins
What percentage of GH is transported in bound form?
50%
What is the purpose of GH traveling bound to protein?
Provides ‘reservoir’ of GH - helps smooth out effects of erratic pattern of secretion and extends half life
How does IGF-1 exhibit neg feedback on GH release?
Via inhibition of GHRH and stimulation of GHIH
What is an additional neg feedback loop of GH?
on GH release from somatotrophs in pituitary
GIve the 3 effects of GH/IGF-1 on bone?
- GH stimulates chondrocyte precursor cells in epiphyseal plates to differentiate into chondrocytes
- During differentiation, the cells secrete IGF-I and become responsive to it
- IGF-1 then acts as an autocrine/paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth
When do epiphyseal plates close and what does this mean for growth?
Close during adolescence under influence of sex steroids, meaning no further longitudinal growth is possible
Give 3 direct effects of GH (that can be descirbed as ‘anti-insulin’ effects)
- increases gluconeogenesis by the liver
- reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue
- makes adipocytes more sensitive to lipolytic stimuli
In these 3 actions, what is the general effect GH is having?
Releasing energy stores to support growth (of bone, heart, brain etc - rather than muscle + fat)
Due to having this ‘anti-insulin’ effect, what hormone does is synergise with?
Cortisol
Why is GH said to be diabetogenic?
It increases blood glucose when present in excess
Give one direct effect of GH which is LIKE insulin, and unlike cortisol
Increases muscle, liver + adipose tissue amino acid uptake and protein synthesis = anabolic while cortisol is catabolic to protein (in this way GH also supports muscle growth)
For growth what 2 hormones are needed?
Insulin and GH
When in your lifetime are the highest rates of secretion of GH?
Teenage years
Describe the secretion rate of GH
Undergoes rapid spontaneous fluctuations as well as increasing/decreasing in response to specific stimuli
What time of day are the highest rates of secretion of GH?
First 2 hrs of sleep (deep delta)
Why is energy diverted to growth during sleep?
General energy requirements are low (vice versa during waking hours GH release is low)
Nutritional control of GH release is mainly mediated via modulation of control of…
GNRH/GHIH release from hypothalamus
Give 5 stimuli for GNRH secretion
- Actual/potential decrease in energy supply to cells
- Increased amino acids in plasma
- Stressful stimuli
- Delta sleep
- Oestrogen + testosterone
Give a few examples of when there may be a decrease in actual/potential energy supply to cells
Fasting + hypoglycaemia (decrease in substrate supply)
Exercise + cold (increased demand for energy)
Give an example of of stressful stimuli
Infection
Psychological stress
Give 4 stimuli for GHIH (somatostatin) secretion
- Glucose
- FFA
- REM sleep
- Cortisol (although may be more to do with increased protein catabolism)
The physiology of growth is a v complex phenomenon affected by which 3 factors?
HORMONES
NUTRITION
GENETICS
Give the 7 hormones/types of hormones involved in growth
GH IGF-1 Thyroid hormones Androgens Oestrogens Glucocorticoids Insulin
What are babies deficient in GH and IGF-1 born like?
They are of normal size (insulin and IGF-II are the hormones dominating intrauterine growth)
What are thyroid hormones particularly important in?
Development of nervous system in utero and early childhood
What do thyroid hormones have a permissive effect on?
GH/IGF-1
What is cretinism?
Condition where children are hypothyroid from birth causing retarded growth from loss of TH’s permissive action on GH
Why does injury and disease stunt growth?
Increased protein catabolism (glucocorticoid effects)
What do genetic factors determine?
Maximum growth
What are the 2 periods of rapid growth in humans?
Infancy
Puberty
What is the nature of growth during infancy?
episodic
What is the cause of growth during puberty?
Androgens and oestrogens
What is the effect of these sex steroids in normal puberty?
Produce spikes in GH + IGF-1 secretion, promoting bone elongation and increased height, weight + body mass before they then terminate growth by causing closure of epipyseal plates
Give 2 conditions which occur as a result is hypersecretion of GH
Gigantism
Acromegaly
What is usually the cause of GH hypersecretion?
Endocrine tumours
What is a characteristic of gigantism?
Pituitary tumour BEFORE epipyseal plates close so excessive long bone growth - patient can be more than 7ft tall
What is a characteristic of acromegaly?
Pituitary tumour AFTER epiphyseal plates close so long bones cannot increase - can still grow in other directions tho so patient will have enlarged hands, jaw + feet
How to treat acromegaly/gigantism?
Surgically remove tumour or somatostatin analogues
