Metabolic rate, growth and disease. Flashcards
What is the effect of growth hormone deficiency/excess in children?
Deficiency leads to dwarfism. Excess leads to gigantism.
Why is there no change in stature in adults with growth hormone excess?
Epiphyses have closed.
What is the effect of excess growth hormone in adults?
Acromegaly - bones become excessively thickened and other tissues overgrow.
What is the effect of growth hormone deficiency in adults?
No obvious disease but replacement increases lean body mass, decreases fat and increases vigour.
From where is growth hormone released?
Anterior pituitary
What is the effect of somatostatin (from hypothalamus) on the secretion of growth hormone?
Supression.
Was is produced by the arcuate nucleus to encourage growth hormone secretion?
Growth hormone releasing hormone
What is produced by target organs to provide negative feedback to the growth hormone system?
IGFs
What are the basic features of growth hormone secretion?
Pulsatile release and more released at night.
There are two forms of growth hormone (20 and 22 kDa). Which predominates?
22kDa
What is the half life of growth hormone?
25 min.
What does ‘diabetogenic’ mean?
Diabetes - causing.
What are the diabetogenic effects of growth hormone?
Acts via tyrosine kinase associated receptor, leading to protein phosphorylation. Rapid effects on liver (increase gluconeogenesis), fat (increase lipolysis), muscle (decrease glucose uptake) and insulin resistance. Long term effects on growth mediated via insulin-like growth factor.
What are IGFs?
Somatomedins - enhance protein synthesis and growth. Can cause hypoglycaemia.
What other factors affect growth?
Insulin (esp. in utero)
Steroids - sex steroids accelerate growth but hasten maturity, glucocorticoids typically slow growth
Thyroid hormone are essential for normal growth and response to GH.
Why are thyroid hormones carried in the blood protein-bound?
Greatly increases half-life: T4 - 8 days and T3 - 1 day.
What is the effect of thyroid hormones on metabolism?
Increases metabolic rate and heat generation via futile cycles and mitochondrial decoupling.
What are the enzymes that deiodinate T4 to T3 and where are they found?
Type I - found in liver, kidney and thyroid, is inhibited by stress and caloric restriction
Type II - in pituitary, CNS and placenta, is constitutive
What are the acute effects of thyroid hormone?
Increases gluconeogenesis and glycogenolysis in the liver.
Causes lipolysis (frees glycerol for gluconeogenesis) and lipogenesis.
Increases proteolysis (produces AA for gluconeogenesis) bu also protein synthesis. Net muscle wasting.
Increases Na/K ATPase activity.
Increased beta receptor expression
Usually no hyperglycemia (insulin control normal).
What are the chronic effects of thyroid hormone?
Crucial for normal brain development.
Deficiency in infancy leads to cretinism and dwarfism.
Later in childhood there is a severe impairment of growth.
TSH drives thyroid hypertrophy, so low TH (and lack of feedback) leads to goitre: common in areas with low iodine.
How might autoimmunity cause hyperthyroidism?
Ab against the TSH receptor may activate it - drives xs TH production.
How might autoimmunity cause hypothyroidism?
Ab against TSHR may destroy the receptor
What is the main natural glucocorticoid?
Cortisol
What is released by the hypothalamus in response to stress and diurnal rhythm?
Corticotropin-releasing hormone
What is the effect of CRH on the anterior pituitary?
Releases Adrenocorticotropic hormone (ACTH).
What is the function of ATCH?
Stimulates adrenal cortex: hypertrophy and cortisol production.
What is the effect of exogenous steroids on ACTH release.
Inhbition due to negative feedback
What are the acute effects of glucocortocoids?
Act via nuclear receptors - induce gene txn.
Inhibit insulin responses and enhance SNS response - targets glucose to brain.
In liver promotes gluconeogenesis and glucose release.
In fat lipolysis (glycerol for gluconeogenesis and FFA for energy)
In muscle protein breakdown for gluconeogenesis.
What are the chronic effects of glucocorticoids?
Immunosuppression
Reduction in inflammation
Stimulate haematopoiesis and GI tract mucosa
Fat redistribution - peripheral to central
Skin thinning, muscle wasting and osteoporosis
Euphoria, psychosis
Cushing’s (xs glucocorticoids)
Addinson’s (adrenocortical insufficiency)
