Endocrine Control of Growth Flashcards
What factors affect physiology of growth?
Genetics
Nutrition
Hormones
What hormones are involved in growth physiology?
GH
IGF-1 - insulin like growth hormone
Thyroid hormone
Insulin
Sex steroids
Cortisol
What are the 2 periods of rapid growth?
Infancy and Puberty
Describe growth in infancy
Foetal period and 8-10 months controlled by thyroid hormones and insulin
GH becomes more significant from 10 months
Describe growth during puberty
Androgens and oestrogens - spikes in GH secretion - increase IDF-I so increase growth
Sex steroids terminate growth as epiphyses fuse in long bones
What does GH and IGF-I promote?
Bone elongation - increased height, weight and body mass
What do sex steroids act to do?
Close epiphyses - stop elongation of bone
What hormones dominate intra-uterine growth?
Thyroid hormone, insulin and IGF-II
Explain congenital hypothyroidism
Babies are born of normal size but cant produce own TH as got from mum in utero
Can get retarded growth and retain infantile facial features
GH levels are normal but low TH supresses action of GH
Does TH have effect on GH?
Has permissive effect on GH
Loss of this action impacts GH action
What is the difference between low TH and low GH in children?
If low TH and normal GH then small and retain infantile proportions
If low GH and normal TH then proportionally normal but small
What type of hormone is growth hormone?
Peptide hormone released from anterior pituitary - somatotropin
Released from somatotroph cells
What is release of GH controlled by?
2 neurohormones with opposing actions -
Growth hormone inhibiting hormone - somatostatin
Growth hormone releasing hormone
Explain the importance of GH
From 10 months is necessary for growth
GH requires permissive action of TH and insulin to stimulate growth - hypothyroidism and poorly controlled diabetes effected
What does GH promote?
Increase in cell size - hypertrophy
Cell division - hyperplasia
What does GH act on?
Tyrosine kinase receptors - phosphorylation of intracellular targets
What are the 2 broad actions of GH?
Growth of long bones - indirect action mediated by IGF-I
Regulation of metabolism - direct action
What is IGF-1?
Insulin like growth factor - somatostatin C
Mediates action of GH
Stimulates glucose uptake in muscle and bone
Secreted in liver in response to GH and has negative feedback loop
How is GH and IGF-1 transported?
Are peptide hormones but like TH and steroid hormone - get transported in blood bound to carrier proteins
How much of GH is in its bound form?
50%
Helps provide a reservoir of GH in the blood to smooth out effects of erratic pattern of secretion and extends half life
Explain the IGF-1 negative feedback loop on GH release
IGF has negative feedback on GH release by inhibiting GHRH and stimulating GHIH (somatostatin)
Additional autocrine - somatotrophs in pituitary
How does GH directly regulate metabolism?
Increases gluconeogenesis by liver
Reduces ability of insulin to stimulate glucose uptake by muscles and adipose tissue
Adipocytes more sensitive to lipolytic stimuli
Increases aa uptake and protein synthesis
Explain the anti-insulin effect of GH
GH is releasing energy stores to support growth - bone is not insulin dependant
Synergises with cortisol
Diabetogenic
What is the similarities and differences between insulin and GH?
Both increase aa uptake and protein synthesis
But inly insulin increases glucose uptake
When does most of GH secretion occur?
Large quantity in pituitaries of adults and child
Majority released in first 2 hrs of sleep - 20 x higher in children
GH during waking hrs is low so might have sleep inducing qualities
What prolongs the action of GH?
Binding to IGF-1 as they bind more tightly to carrier proteins than GH so less vulnerable to degradation
IGF-1 remains relatively constant plasma levels
What stimuli increase GHRH secretion?
Actual or potential decrease in energy supply to cells
Increased amounts of aa in the plasma
Physical stress and illness
Delta sleep
Oestrogen and testosterone
How does decrease in actual or potential energy supply to cells increase GHRH secretion?
In fasting and hypoglycaemia decrease in substrate supply
In exercise and in cold increase demand for energy which all increase GH
What stimuli increase GHIH - somatostatin secretion?
Glucose
FFA
Ageing
Cortisol
What are the types of hypersecretion of GH?
Gigantism and Acromegaly
Endocrine tumours usually the cause
What is gigantism?
Excess GH due to pituitary tumour before epiphyseal plates have closed - excessive growth
What is acromegaly?
Excess GH due to pituitary tumour after epiphyseal plates have closed
Long bones cant increase so no longitudinal growth but grow in other directions
Enlarged hands and feet
What can unusually small stature be due to?
A deficiency of GHRH
A deficiency of GH
Genetic mutations of GH
Precocious puberty
Hypothyroid dwarfism
What is precocious puberty?
Excess GnGH from hypothalamus stimulates puberty via promoting sex hormone release
Stunted growth because long bones fuse early
How does injury and disease stunt growth?
Increased protein catabolism - glucocorticoid effects
What can gestational diabetes lead to?
Very big babies though excess anabolism by foetal insulin
