6. Adrenal Cortex: Hormones and Physiology Flashcards
adrenal gland anatomy
on top of kidneys inner medulla (10%) outer cortex (90%)
adrenal cortex layers
outer zona glomerulosa
middle zone fasciculata
innermost zona reticularis
cells in different layers have different enzymes, so produce different hormones
zona glomerulosa
contains 18-hydroxylase enzyme - produces aldosterone
zona fasciculata
contains 17a-hydroxylase enzyme
cortisol is synthesised here
androgens are also synthesised here
how is cortisol secretion controlled?
hypothalamus secretes CRH
CRH causes anterior pituitary to release ACTH
ACTH acts on adrenal cortex to produce cortisol
cortisol negatively feeds back to hypothalamus to reduce CRH secretion
ACTH secretion characteristics
pulsatile
peaks in early morning (waking)
lowest levels in middle of night
secretion increases at times of stress
cortisol shows same pattern, but peak and trough ~2 hours later
pattern is related to sleep-wake cycles (different in shift workers)
transport of glucocorticoids (cortisol)
10% free in blood (Active)
75% bound to corticosteroid binding globulin (CBG)
15% bound to albumin (15%)
pregnancy and CBG
compensatory increases in circulating plasma cortisol concentrations
free cortisol remains stable as CBG increases
metabolism of adrenal steroids
occurs mostly in the liver
glucuronidated to form water soluble forms, so can be excreted in urine
effects of glucocorticoids
same as other steroid hormones
action is on intracellular receptors, altering gene expression
hence, delay before effect is seen (hours-days)
sometimes cortisol effects are rapid: ACTH inhibition
also can stimulate aldosterone receptors
effects of cortisol
opposite to insulin
antagonises effects of insulin on cellular glucose
stimulates glycogenolysis
stimulates hepatic gluconeogenesis
stimulates lipolysis and mobilisation of fatty acids (potentiates effects of GH and catecholamines)
cortisol in excessive concentrations
causes fat synthesis and deposition in novel anatomical sites
especially: face, trunk and intrascapular region of shoulders
cortisol in liver
stimulates amino acid uptake
enhanced gluconeogenesis
cortisol in periphery
inhibits amino acid uptake and protein synthesis
net loss of skeletal protein
how can glucocorticoids affect the body’s defence systems?
suppress lymphoid tissue (reduces antibody production, inhibit cellular immune system)
stabilises leucocyte membranes + reduces release of proteolytic enzymes
inhibits phospholipase A2 - reduces synthesis of inflammatory mediators
glucocorticoid response to stress
maintain the enhanced supply glucose
may be required for prolonged response se to stressor, and suppress inflammatory response
what happens at times of injury?
pain alerts sufferer to damage
oedema dilutes toxins and immobilises/stabilises joints
infiltration by leucocytes destroys invading cells
tissue repair is enhanced by prostaglandins
how glucocorticoids work
adrenocortical stress response decreases inflammatory response
removes pain and decreases immobilisation induced by oedema
steroid-induced sedation: lack of awareness of severity
overall effect = individual can continue to perform, despite injury
control of mineralocorticoid secretion
aldosterone secretion is relatively uninfluenced by ACTH
major controlling factor = RAAS
aldosterone is inhibited by atrial natriuretic peptide (ANP)
what can stimulate aldosterone secretion?
renin-angiotensin-aldosterone system trauma anxiety hyperkalaemia hyponatraemia
aldosterone actions
specific intracellular receptors which cause expression of ion channels transporting Na+ and K+ across the cell membrane
stimulates Na+ reabsorption in distal tubule, in exchange for K+ or H+
aldosterone and Na+ in plasma
by controlling Na+ reabsorption in kidney, aldosterone controls Na+ concentration in plasdma
water reabsorption in the collecting duct is also affected, via ADH secretion
interaction of RAAS, aldosterone and ADH controls blood pressure and volume
pharmacological uses of glucocorticoids
eg hydrocortisone
replacement therapy
immunosuppressive/anti-inflammatory (asthma, arthritis)
treatment for proliferative conditions (leukaemia)
pharmacological uses of mineralocorticoids
used only in replacement therapy
aldosterone has short half life, so unsuitable
drug of choice = fludrocortisol
adverse effects of glucocorticoid use
steroids may suppress wound healing and exacerbate infections ]
long term use in children can inhibit growth
long term use in adults can result in osteoporosis
diabetes mellitus and symptoms of Cushing’s often seen
suppression of HPA axis
