Normal growth and Clinical aspects Flashcards
What factors regulate growth? (7)
Growth hormone
Thyroid hormones
Insulin
Sex steroids (esp. at puberty)
Availability of nutrients
Stress
Genetics
What is growth hormone?
A peptide hormone produced by the anterior pituitary
Release is controlled by Growth hormone inhibiting hormone (GHIH) and Growth hormone releasing hormone (GHRH)
What are the two broad actions of growth hormone?
Growth and development (indirect action)
Regulation of metablism (direct action)
When does GH become important in growth and development timescale? And what does GH require for stimulation of growth?
GH is necessary for growth and development of the child but only really after 8-10 months of life - before this nutritional intake has a more dominant influence.
GH requires permissive action of thyroid and insulin before it will stimulate growth - this is why children with untreated hypothyroidism or poorly controlled diabetes have stunted growth despite normal GH levels
What is growth in the foetal period and first 8-10 months of life largely controlled by?
nutritional intake
Growth-promoting effect of GH is mediated through stimulation of what?
cell size (hypertrophy)
cell division (hyperplasia) in its many target tissues
Describe Growth and development and the indirect effect GH has on it
The effect of GH on growth is almost entirely indirect, being achieved through the action of an intermediate known as insulin-like growth factor-I (IGF-1) aka somatomedin C as it mediates the action of GH.
IGF-I is secreted by the liver, and many other cell types, in response to GH release, and IGF-1 controls GH release through a negative feedback loop.
GH and IGF-I are peptide hormones - they are transported in the blood bound to carrier proteins. ~50% of GH is in the bound form. This helps to provide a “reservoir” of GH in the blood which helps to smooth out the effects of the erratic pattern of secretion and extends half life by protecting from excretion in the urine.
What is IGF-II
IGF-II = other growth factor that exists but it’s functional importance appears to limited to the foetus and neonate.
How does IGF exhibit negative feedback on GH release?
via inhibiting GHRH and stimulating GHIH
GH/IGF-I effects on bone growth
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 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.
Why do epiphyseal plates close during adolescence?
influence of sex steroid hormones - longitudinal bone growth is no longer possible when they close
How does GH regulate metabolism?
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 all of these GH is releasing energy stores to support growth
Also increases amino acid uptake and protein synthesis in almost all cells - anabolic effect
What does bone not require for growth?
Insulin
Summary of Direct effect of GH
Mobilises glucose stores to increase blood [glucose]
Inhibits the action of insulin (by reducing the 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 the body, sparing glucose and again augmenting increased blood [glucose]
Promotes amino acid uptake to cells, supporting protein synthesis
1-3 might seem strange given that GH is anabolic and concerned with GROWTH, but remember that only muscle and adipose tissue are insulin sensitive. Other tissues do not require insulin for glucose uptake, so bone and brain development are hugely supported by the actions of GH, as is muscle development due to effect on aa uptake.
Secretion rate of GH
Undergoes rapid spontaneous fluctuations as well as increase or decreases in response to specific stimuli
Majority of GH released during first 2 hours of sleep (deep delta sleep). 20X increase in GH secretion in children during this period.
GH release during waking hours is low.
What controls Growth hormone secretion?
heavily influenced by nutritional status
Nutritional control of GH release is mainly mediated via modulation of control of GHRH/GHIH release from the hypothalamus.
Stimuli that increase GHRH secretion (5)
Actual or potential decrease in energy supply to cells
Increased amounts of amino acids in the plasma
stressful stimuli - infection, psychological stress
delta sleep
oestrogen and testosterone
Stimuli that increase GHIH (Somatostatin secretion) (decrease GH)? (4)
Glucose
Free FA’s
REM sleep
Cortisol
3 factors affecting growth
hormones
nutrition
genetics
Which hormones affect growth? (6)
GH
IGF-1
Thyroid hormones
Sex hormones (minor influence until puberty)
Glucocorticoids
Insulin
Discuss Thyroid Hormones
Essential for normal growth, particularly important for development of the N.S in utero and early childhood.
Effects are permissive to GH/IGF-1
Have widespread effects on ossification of cartilage and teeth maturation as well as the contours of the face and the proportions of the body.
What is cretinism?
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
When are the 2 periods of rapid growth in humans?
Infancy
Puberty
What is growth like in puberty?
Due to androgens and oestrogens - produce spikes in GH secretion that increase IGF-1 which increases growth
Same sex steroids 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.
What is growth like during infancy?
Growth spurts of 2.5cm in a few days and then nothing ie episodic, mechanism unknown
Gigantism
excess GH due to a pituitary tumour before epiphyseal plates of long bones closes causes excessive growth, may be more than 7ft tall (210cm), called pituitary giants.
Acromegaly - hypersecretion of GH
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.
What is a classic sign of acromegaly?
In adults feet should NOT get bigger but they do in acromegaly so this is a classic sign
normal height but enlarged hands and feet and facial features
How do you treat acromegaly?
surgery to remove tumour or somatostatin analogues
