6. Adrenal Cortex: Hormones and Physiology

Question 1

adrenal gland anatomy

Answer 1

on top of kidneys 
inner medulla (10%)
outer cortex (90%)

Question 2

adrenal cortex layers

Answer 2

outer zona glomerulosa
middle zone fasciculata
innermost zona reticularis
cells in different layers have different enzymes, so produce different hormones

Question 3

zona glomerulosa

Answer 3

contains 18-hydroxylase enzyme - produces aldosterone

Question 4

zona fasciculata

Answer 4

contains 17a-hydroxylase enzyme
cortisol is synthesised here
androgens are also synthesised here

Question 5

how is cortisol secretion controlled?

Answer 5

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

Question 6

ACTH secretion characteristics

Answer 6

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)

Question 7

transport of glucocorticoids (cortisol)

Answer 7

10% free in blood (Active)
75% bound to corticosteroid binding globulin (CBG)
15% bound to albumin (15%)

Question 8

pregnancy and CBG

Answer 8

compensatory increases in circulating plasma cortisol concentrations
free cortisol remains stable as CBG increases

Question 9

metabolism of adrenal steroids

Answer 9

occurs mostly in the liver

glucuronidated to form water soluble forms, so can be excreted in urine

Question 10

effects of glucocorticoids

Answer 10

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

Question 11

effects of cortisol

Answer 11

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)

Question 12

cortisol in excessive concentrations

Answer 12

causes fat synthesis and deposition in novel anatomical sites
especially: face, trunk and intrascapular region of shoulders

Question 13

cortisol in liver

Answer 13

stimulates amino acid uptake

enhanced gluconeogenesis

Question 14

cortisol in periphery

Answer 14

inhibits amino acid uptake and protein synthesis

net loss of skeletal protein

Question 15

how can glucocorticoids affect the body’s defence systems?

Answer 15

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

Question 16

glucocorticoid response to stress

Answer 16

maintain the enhanced supply glucose

may be required for prolonged response se to stressor, and suppress inflammatory response

Question 17

what happens at times of injury?

Answer 17

pain alerts sufferer to damage
oedema dilutes toxins and immobilises/stabilises joints
infiltration by leucocytes destroys invading cells
tissue repair is enhanced by prostaglandins

Question 18

how glucocorticoids work

Answer 18

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

Question 19

control of mineralocorticoid secretion

Answer 19

aldosterone secretion is relatively uninfluenced by ACTH
major controlling factor = RAAS
aldosterone is inhibited by atrial natriuretic peptide (ANP)

Question 20

what can stimulate aldosterone secretion?

Answer 20

renin-angiotensin-aldosterone system 
trauma 
anxiety 
hyperkalaemia
hyponatraemia

Question 21

aldosterone actions

Answer 21

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+

Question 22

aldosterone and Na+ in plasma

Answer 22

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

Question 23

pharmacological uses of glucocorticoids

Answer 23

eg hydrocortisone
replacement therapy
immunosuppressive/anti-inflammatory (asthma, arthritis)
treatment for proliferative conditions (leukaemia)

Question 24

pharmacological uses of mineralocorticoids

Answer 24

used only in replacement therapy
aldosterone has short half life, so unsuitable
drug of choice = fludrocortisol

Question 25

adverse effects of glucocorticoid use

Answer 25

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