adrenals Flashcards
adrenal corticosteroids: recall adrenal corticosteroid synthesis; explain the homeostatic control and transport in the circulation of adrenal corticosteroids; recall the mechanisms of action of adrenal corticosteroids and their physiological effects
glucocorticoid synthesis: backbone molecule
synthesised from cholesterol in same way as pituitary
glucocoticoid synthesis: diversity
different enzymes in different cortex regions causes different hormones such as cortisol or aldesterone produced
aldosterone vs cortisol
remove one enzyme and replace with another downstream; pregnenolone diverted to progesterone in aldosterone synthesis
how are steroid hormones transported in blood
lipid soluble so rapidly diffuse into blood; weak binding to proteins in blood or strong binding to specific binding proteins e.g. CBG (cortisol binding globulin)
% cortisol unbound
10%
% aldosterone unbound
40%
cortisol in blood
higher levels in morning than evening
aldosterone in blood
1000-fold decrease vs cortisol
which receptors do cortisol bind to
glucorticoid receptors and aldosterone (mineralcorticoid) receptors
which receptor does aldosterone bind to
aldosterone (mineralcorticoid) receptors
function of 11bhsd2 enzyme
breaks down cortisol
why is aldosterone relevant
some tissues have high levels of 11bhsd2 enzyme so only aldosterone can enter and influence activity
what tissues have high 11bhsd2 levels
kidneys, placenta
define renin-angiotensin system
hormone system that regulates blood pressure and fluid balance in kidney (nephron)
what cells produce renin
granular cells
what factors increase renin production
low renal blood pressure, increase in renal sympathetic nervous activity, macular densa cells in distal convoluted tubule acting as Na+ sensors: if low Na+ renin production increases
renin function
allows reabsorbtion Na+, therefore H2O reabsorbed, therefore blood pressure restored
what protein does renin activate and what does this produce
angiotensinogen producing angiotensin I
what does ACE do in the lungs
converts angiotensin I to angiotensin II
function of angiotensin II
stimulates aldosterone production in zona glomerulosa
what also stimulates aldosterone production
low Na+ and K+ levels
how is homeostatic control ensured
hypothalamo-pituitary-adrenal axis
aldosterone mechanism of action: location
acts on late distal tube and collecting duct
aldosterone mechanism of action
aldosterone causes reabsorption of Na+ → creates more Na+ ion channels → Na+ diffuses through Na+ ion channel in tubule lumen endothelium down conc gradient → to ensure conc. gradient, aldosterone increases number of Na+/K+ ATPase pumps in blood endothelium → more Na+ reabsorbed and K+ exchanged into tubule lumen → more H2O reabsorbed also
cortisol mechanism of action
binds to glucorticoid receptor in cell, influences transcription of specific proteins in nucleus
MR and GR activation for maximal effects in normal physiology and stressful physiology
full MR activation and partial GR activation; both full when under stress
cortisol effect on glucose
stress hormone so ensures glucose readily available and lots of stores of glucose; increases gluconeogenesis and glycogenesis; decrease glucose from entering storage sites in skeletal muscle or fats; prevents fatty acids staying in adipocytes; decreases blood flow, decreases GLUT 4
cortisol: physiological actions
pro-memory at dentate gyrus in hippocampus: serotonin innervation promotes granule cell division and memory formation; cortisol upregulates serotonin 5HT 1A receptors
cortisol: supra-physiological actions
promotes anti-inflammatory and immunosuppressive effects; anti-memory effects if chronic stress as hippocampus destroyed by cortisol, impacting long-term memory formation
adrenal androgens
sex steroids, weak biological activity but converted to more active androgens by enzymes in peripheral tissues
define steroid
hormone which precursor is cholesterol (C27, 4 rings)
how is cholesterol converted to cortisol
cholesterol → progesterone → 17-OH-progesterone → 11-deoxycortisol → cortisol
how is cholesterol converted to aldosterone
cholesterol → progesterone → 11-deoxy-corticosterone → corticosterone → aldosterone