Normal growth and clinical aspects Flashcards
Where is GH released from and what is its main action?
anterior pituitary
promote growth
What is another name for GH?
somatotrophin
What is meant by GH being species specific?
only human GH can be used in GHD
used to use GH direct from human pituitary
due to CJD infection now use recombinant
What 2 hormones have a permissive effect to GH and hence are essential for normal growth?
insulin
thyroid hormone
What type of hormone is GH but what is the exception to the normal rule of this class of hormones?
peptide
about 50% circulates bound to carrier proteins
Role of GH in adults
maintenance of tissues and their energy supply
When does GH take over as the main influence on growth and what predominates before this?
8-10 months
nutritional intake
Hyperplasia
increased cell division
hypertrophy
increased cell size
Is GH effect on growth direct or indirect?
indirect
What is the name of the intermediate which allows growth?
IGF1
What is another name for IGF-1?
somatomedin
What is IGF-1 structure similar to?
proinsulin
Name 3 ways IGF-1 is insulin like
hypoglycaemic qualities
similar structure to proinsulin
binds to receptors similar to insulin receptor
Where is IGF-1’s hypoglycaemic qualities limited to and why?
muscle
liver and adipose tissue have few IGF-1 receptors
Where is IGF-1 released from and in response to what?
LIVER and other tissues eg bone
increased GH from anterior pituitary
How does IGF-1 control GH
negative feedback loop
What is IGF-2 role?
limited to foetus and neonatal
Explain the IGF-1 and GH negative feedback loop
IGF-1 inhibits GHRH and stimulates GHIH
GH on GH release from somatotrophs in pituitary eg self regulation
What does GH do to prechondrocytes in the epiphyseal plate?
stimulate them to become chondrocytes
What do these chondrocytes secrete and what is the consequence of this
IGF-1
become IGF-1 responsive
Does IGF-1 act as autocrine/paracrine/endocrine in bone growth?
autocrine and paracrine
What happens In bone growth once IGF-1 is released and then bone is now IGF-1 sensitive?
chondrocytes undergo cell division and produce cartilage which is the foundation for bone growth
Why does the epiphyseal plate close and what is the consequence of this?
puberty/adolescence due to sex hormones
no more longitudinal bone growth
What are the direct effects of GH?
increase gluconeogenesis by liver
reduce ability of insulin to stimulate glucose uptake by muscle/adipose
adipocytes more sensitive to lipolytic stimuli
release energy stores to support growth
Is GH said to be anti or pro insulin?
anti
How is 1 way that GH is like insulin and not like cortisol
increase muscle, liver and adipose tissue amino acid uptake and protein synthesis –> anabolic
Where are GHRH and GHIH secreted from?
hypothalamus
Explain the differences in the basal plasma and 24 hour mean rates of GH in children and adults
basal GH - same
24 hour mean - children higher due to spikes of secretion
What phase of sleep is GH highest and why?
deep delta sleep
general energy requirement low and energy diverted to growth
Why must repeated hormone measurements be taken?
to get a true picture of hormone status due to spikes
Does IGF-1 have spikes or constant? Result of this?
constant
buffers pulsatile variance in GH levels
Advantage of 50% of GH bound to carrier proteins
reservoir of GH
smooths out effects of erratic pattern of secretion
How would you describe GHIH secretion?
tonic
slow and responsive to needs
5 things that increase GHRH secretion and hence increase GH
actual or potential decrease in energy supply increased amino acids in plasma delta sleep stressful stimuli eg infection, stress oestrogen and androgens
Why does an actual or potential decrease in energy stimulate GHRH secretion?
GH needed for maintenance of tissue and energy supply
in fasting/hypoglycaemia decreased substrate supply
exercise and cold increase energy demand
all stimulate increase in GH
Why does increased amino acids in plasma increase GH?
protein meal
GH promotes amino acid transport and protein synthesis by muscle and liver
4 stimuli which increase GHIH secretion and hence decrease GH
cortisol
glucose
FFA
REM sleep
Why is cortisol inhibitory on growth?
promotes GHIH
increase protein catabolism
3 important factors in the physiology of growth
hormones
nutrition
genetics
Name some hormones important in growth
thyroid hormone, insulin, GH, IGF1, oestrogen, cortisol, androgens
When do sex hormones start playing a major role in growth?
puberty
What is TH important for in growth?
permissive to IGF-1 and GH
nervous system development in utero and childhood
ossification of cartilage and teeth maturation
contours of face
What is cretinism?
hypothyroid - infant facial features
decreased growth
hypothyroid dwarf
Why do injury and disease stunt growth?
increased catabolism
glucocorticoid effects
what are the 2 periods of rapid growth
infancy
puberty
Explain infancy rapid growth
can grow 2.5cm in a few days then nothing
EPISODIC
Explain puberty rapid growth
androgens and oestrogens
spikes in GH and IGF-1
same hormones terminate growth
What hormones influence bone elongation before the epiphyseal plates fuse?
GH and IGF-1
What hormones cause the epiphyseal plates to fuse?
sex hormones
What is usually the cause of hypersecretion of GH?
endocrine tumours
Cause of gigantism
excess GH before epiphyseal plates fuse
Cause of acromegaly
excess GH after epiphyseal plates fuse
What happens in acromegaly?
cannot increase longitudinal bone growth
grow in other directions eg hands and feet
What is adults feet increasing in size a sign of?
acromegaly
Treatment for acromegaly
remove tumour
GHIH analogues
List some reasons for reduced growth
precocious puberty genetic mutations deficient in GHRH GH secreting cells abnormal end organ unresponsive to GH hypothyroid children
How do children deficient in GH or TH differ in proportions?
both small
hypothyroid - infant proportions
GH - small but normal proportions
