Normal Growth and Clinical Aspects COPY Flashcards
growth is regulated by a number of factors
what are they?
- Growth hormone release from anterior pituitary – which in turn is regulated by the balance of GHRH vs GHIH release from the hypothalamus. Doesnt cause much growth on its own, better supported when there is insulin and thyroid hormone
- Thyroid hormones
- I nsulin
- Sex steroids (esp. at puberty) - more growth around puberty
- Availability of nutrients - nutrients provide substrates for growth
- Stress - Stress has a complicated effect on growth – increased release of GH but also cortisol which is catabolic so breaks down things
- Genetics
What type of hormone is GH?
Where is it release and by what cells?
What is it also known as?
GH is a peptide hormone
released from the anterior pituitary
Aka somatotropin
Released from somatotroph cells (“troph” relating to growth)
What is the release of GH controlled by?
GH release is controlled via the release of two hypothalamic neurohormones with opposing action
GH release is controlled via the release of two hypothalamic neurohormones with opposing action
what are they?
Growth Hormone Inhibiting Hormone (GHIH) (aka Somatostatin (“statin” relating to stasis = static/stopped))
and
Growth Hormone Releasing Hormone (GHRH)
The balance of GHRH : GHIH is determined by the myriad of factors that impinge on the hypothalamus
GH has a wide spectrum of biological activity that can be definied by two broad categories:
what are they?
- Growth and development (indirect action) - Stimulates another hormone that causes elongation of long bones
- Regulation of metabolism (direct action) - direct action on regulating metabolism and influences metabolism of cells
What recpetors do GH bind to?
Binds to tyrosine receptor like insulin, switches intracellular proteins on and off
When does GH affect growth and development of a child?
GH is necessary for growth and development of the child
Growth in the foetal period and the first 8-10 months of life is largely controlled by nutritional intake, but thereafter GH becomes the dominant influence on the rate at which children grow
Growth hormone doesn’t really kick in till end of first year of life
Little role in growing the very young child
what does GH require in order to cause growth and development?
GH requires permissive action of thyroid hormones and insulin before it will stimulate growth
How does hypothyroidism, or poorly controlled diabetes affect the growth of a child?
Children with untreated hypothyroidism, or poorly controlled diabetes, have stunted growth despite normal GH levels
This is because they would not have the permissive effect of thyroid or insulin on GH
Does GH secretion happen in adults, if so why?
GH secretion continues throughout adult life as it is continues to be essential in the maintenance and repair of tissue
What effect does GH have on cells allowing growth?
Growth-promoting effect of GH is mediated through stimulation of both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues
The effect of GH on growth is almost entirely ________
indirect
The effect of GH on growth is almost entirely indirect, so how is growth achieved?
it is 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-1 has structure very similar to _________
pro-insulin
What receptors doe IGF-1 bind to and what effects does it cause?
binds to receptors very similar to the insulin receptor
has hypoglycaemic qualities (hence “insulin-like”) although action is limited to glucose uptake in muscle
Liver and adipose tissue have few IGF receptors
WHat secretes IGF-1, when is it released and what is its effect on 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.
What is IGF-II
IGF-II also exists but it’s functional importance appears to limited to the foetus and neonate
How is GH and IGF-1 transported in the blood?
GH and IGF-I are peptide hormones, but like steroid and thyroid hormones, they are transported in the blood bound to carrier proteins
~50% of GH is in the bound form
What is the benefit of GH and IGF-1 being boudn to carrier proteins in the blood
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
How does IGF cause engative feedback on GH?
IGF exhibits negative feedback on GH release both via inhibiting GHRH and stimulating GHIH (somatostatin)
Additional negative feedback loop of GH on GH release from somatotrophs in pituitary
why does GH increase BG
as it blocks insulin
What are the effects of GH/IGF-I on bone growth?
- GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes (a cell which has secreted the matrix of cartilage and become embedded in it)
- 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
what is this image showing?
Fluctuation in level of growth hormone (GH) in a 7 year old child
Repeated measurements over 24 hours are essential when evaluating GH release, in order to get a true picture of hormone status
Despite GH spikes, plamsa levels of IGF-1 remain relatively constant suggesting IGF-1 buffers the pulsatile variance in GH levels
How does the influence of different hormones change throughout life?
Different periods of growth are dominated by different hormones
Sex hormones influence is minor until puberty when they dominate the growth spurt
GH influence is also minor during foetal life. Babies born deficient in GH and IGF-1 are of normal size. Insulin and IGF-II may dominate intrauteriene growth
What is congenital hypothyroidism and what effects does it have?
Congenital hypothyroidism is a condition where children are deficient in TH in utero
They have retarded growth because of the loss of TH’s permissive action on GH. They retain infantile facial features. GH levels are normal
Reflects maternal iodine deficiency during pregnancy. Found in regions of endemic iodine deficiency
describe child growth in this picture
Hypothyroid children retain infantile proportions, whereas children deficient in GH are proportionally normal, just small
How does injury or disease affect growth? and what happens after the injury or disease?
Injury and disease stunt growth because it causes increased protein catabolism (glucocorticoid effects)
period of catch up where the child returns to normal height
what rapid growth occurs in puberty?
due to androgens and oestrogens, produce spikes in GH secretion that increased IGF-I which leads to increased growth. The 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
how is gigantism caused?
XS GH due to a pituitary tumour before epiphyseal plates of long bones close = excessive growth, may be more than 7ft tall (210cm), called pituitary giants
how is agromegaly caused?
XS 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.
In adults feet should NOT get bigger = classic sign of ACROMEGALY
what would the body be like of someone with acromegaly?
normal neight but enlarged hands and feet and facial features
