Metabolic rate & growth Flashcards
What does excess growth hormone lead to?
gigantism
Why does stature not change in adults with abnormal growth hormone levels?
epiphyses are closed
excess = acromegaly
How does the hypothalamus affect regulation of growth hormone?
Hypothalamus integrates signals driving or suppressing expression
What does GRH do?
increases secretion from anterior pituitary.
What does somatostain do?
suppresses secretion from anterior pituitary.
What is the purpose of target organs producing IGFs?
provide feedback inhibition
When is GH secreted most?
Night time, in pulses
What are the 2 splice variants of growth hormone and which form predominates?
20 and 22 kDa
22kDa form predominates
but may have fewer of the acute metabolic actions
What is the half life growth hormone?
25 minutes
What are the diabetogenic effects of GH?
Liver: ↑ gluconeogenesis
Fat: ↑ lipolysis
Muscle: ↓ glucose uptake
Insulin resistance
What are IGF1 and IGF2?
IGFs = Somatomedins
IGF1 is the main active one
IGF2 not controlled by GH
What can IGF1 cross react with?
insulin
What other factors affect growth?
Insulin (especially in utero)
Steroids:
- Sex steroids accelerate growth, but hasten maturity
- Glucocorticoids typically slow growth
Thyroid hormones are essential for normal growth and response to GH
What are the two forms of thyroid hormone?
Two forms: T3 (triiodothyronine) which is more active and T4 (thyroxine) which is more abundant
How are they thyroid hormones carried in the blood?
tightly bound to proteins e.g thyroid binding globulin and transthyretin
How much longer do thyroid binding proteins prolong half lives?
T4 8 days, T3 1 day
What do thyroid hormones do?
Increase metabolic rate, and heat generation
Also essential for normal growth and development.
Where is type I TH enzyme found?
found in liver, kidney and thyroid, is inhibited by stress and caloric restriction.
Where is type II TH enzyme found?
In pituitary, CNS, & placenta, is constitutive
What are some acute effects of thyroid hormone?
Acutely, increase basal metabolic rate and heat production, via “futile cycles” and mitochondrial decoupling
Increases gluconeogenesis and glycogenolysis in the liver.
Causes both lipolysis (to free glycerol for gluconeogenesis), and lipogenesis.
Increases proteolysis (to produce AA for gluconeogenesis), but also protein synthesis. Net muscle wasting.
Increases Na,K ATPase activity (and leak?)
Increased β receptor expression
Usually no hyperglycaemia (insulin control normal)
What are some chronic effects of thyroid hormone?
Crucial for normal brain development and growth
Deficiency in infancy leads to cretinism (congenital hyperthyroidism) and dwarfism
Later in childhood there is severe impairment of growth: catch-up growth possible
TSH drives thyroid hypertrophy, so low TH (and lack of feedback) leads to a goitre: common in areas with low environmental iodine (e.g. “Derbyshire neck”)
How can autoimmunity cause hyperthyroidism?
Antibodies against the TSH receptor may activate it, driving excess TH production and cause hyperthyroidism
What are the symptoms of hyperthyroidism?
Weight loss, tremor, sweating, tachycardia, dislike of hot weather
In Graves disease, exophthalmos, double vision and pretibial myxoedema
What are the symptoms of hypothyroidism?
Weight gain, hypothermia, tiredness, constipation, skin thickening & oedema, bradycardia, dislike of cold weather. Secondary anovulation
How can autoimmuinity cause hypothyroidism?
Antibodies that destroy TSH receptors or other thyroid targets cause hypothyroidism (e.g. Hashimoto’s thyroiditis)
What is the pathway of cortisol production
stress+diurnal rhythm>hypothalamus>CRH>anterior pituitary>ACTH>adrenal cortex>cortisol production
What are the acute effects of glucocorticoids?
Inhibit insulin responses, and enhance SNS responses
Targets glucose to brain: other organs use fats
In liver, promotes gluconeogenesis and glucose release
In fat, lipolysis (glycerol for gluconeogenesis, FFA for energy)
In muscle, protein breakdown for gluconeogenesis
What are some Chronic Effects of Glucocorticoids?
Immunosuppression
Reduction in inflammation and cytokine production
Stimulate haematopoiesis and GI tract mucosa
Fat redistribution – peripheral to central
Skin thinning, muscle wasting, osteoporosis
Complex CNS effects: euphoria to psychosis!
What is the disease caused by excess glucocorticoids called?
Cushing’s disease
What is the disease cause by adrenocortical insufficiency?
Addison’s disease
