Lec 10 - Adrenal Glands Flashcards
three layers in cortex of adrenal gland
zona glomerulosa
zona fasciculata
zona reticularis
the 2 corticosteroid hormones made in adrenal gland
mineralcorticoids
glucocorticoids
where is mineralcorticoids produced
zona glomerulosa
where is glucocorticoids produced
zona fasciculata
what does zona reicularis produce
precursors to androgens
what is main mineralcorticoid
aldosterone
whatis main glucocorticoid
cortisol
what do all corticosteroids start off as
cholesterol
what is rate limiting step in steroid biogenesis
first step = cholesterol to pregnenolone
2 mechanisms of action of glucocorticoid
genomic and non genomic
in the cell, what is glucocorticoid receptor linked with
heat shock proteins (molecular chaperones)
when steroid receptor complex binds to response elemen, what action does it have
alters protein production
how is non genomic different to genomic
- much faster
- response to stress
- binds to Gi GPCR in membrane
how does non genomic action work
Gi
decreases cAMP production
decreased Ca2+ into cell
and increased K+ out of cell
= decreased excitability
why do GCs have more widespread effects
more receptors throughout the body
what are the general effects of GCs
controls metabolic effects
anti inflammatory effects
immunosuppresive effects
effects of MCs
controls water and electrolyte balance
and
blood pressure homeostasis
which pituitary gland does corticotropin releasing hormone act on
anterior
what does ant pituitary release
adrenocorticotropic hromone
ACTH
how does cortisol -vely feedback
acts on APG
and Hypothal
how does ACTH trigger cortisol synth and release
binds to Gs receptor
inc cAMP
inc PKA
binds to response elements
which allows synthesis of cortisol
3 wayss GCs have antiinflammatory effects
Stabilises lysosomal membranes
Decreases permeability of capillaries
Decreases migration of white blood cells (and release of prostaglandins, cytokines etc)
3 more direct effects on immune system that have anti inflammatory effects
- Suppression of the immune system by
Reduction in T cells and antibodies - Reduction of fever by
reduces production of IL-1 - Rate of healing as it increases
Amino acids, glucose, fatty acids available for repair of tissues.
how can GCs be used therapeutically (anti inflammatory effects)
Blocks inflammatory response in allergic reactions
Decreases white blood cells in blood
Prevents rejection of transplanted tissues and organs
Suppression of immune system
metabolic effects of GCs
- Indicates to catecholamines to exert lipolytic effects
- Indicates to glucagon to exert calorigenic effects
- Increased gluconeogenesis, particularly in the liver
-Increased storage of glycogen in liver and in muscle - Uptake and use of glucose in muscle and adipose tissue decreased
- reduction in protein stores
- increased liver and plasma AAs
how does aldosterone increase blood pressure
Causes retention of Na+
Increased release of potassium
In renal tubular epithelial cells
how can aldosterone alter water/electrolyte balance
- controls Na+ and K+ transport in
Salivary glands
Sweat glands
Intestines (colon)
name a competitive inhibitor of MC receptors
Spironolactone
= used as diuretic, and hypertensive effects
what causes increase in MC release
- Increased K+ in kidney tubules
- Increased activity of renin-angiotensin system
- ACTH
how do MCs genomic effects work
- when it acts on nuclear receptors
- increases Na+ channel proteins
- and Na/K ATPase increases
(= allows increased absorption of Na and release of K)
which synthetic steroids have both GC and MC activity
- Hydrocortisone
- Prednisolone, prednisone
which synthetic steroids have pure GC activity
Dexamethasone
and others but jus allow it man
which synthetic steroids have pure MC activity
Fludrocortisone
disorder from excessive cortisol release
Cushing’s Syndrome
what can cushings syndrome be caused by
- Tumour of the pituitary gland, adrenal glands
- Tumours or cancer arising elsewhere in the body (ectopic ACTH producing tumors)
what disorder caused by INADEQUATE LEVELS OF CORTISOL
Addisons disease
causes of addisons disease
Adrenal insufficiency due to adisorderof the adrenal glands themselves (primary adrenal insufficiency)
Inadequate secretion of ACTH by the pituitary gland (secondary adrenal insufficiency)
what used to treat cushings
GC receptors antagonists
Mifepristone
why does mifeprestone need to be used carefully in women
is also a progesterone receptor antagonist
what is new GC receptor antagonist that is in clinical trials
Relacorilant
selectively binds to the GR without anti-progesteronereceptor effects
addisons disease symptoms
Appetite loss
Discolouration of the skin
Dehydration
Increased thirst and need to urinate frequently
Salt cravings
Oligomenorrhoea
No energy or motivation, low mood
Sore / painful, weak muscles and joints
how is addisons disease treated
- hydrocortisone
- prednisone
etc
used to replace cortisol
what is used to replace aldosterone in aldosterone deficiency
Fludrocortisone acetate
where can steroids have side effects
- muscle disease
- bone impairment
- skin diseases
- oculopathy
- cardiovasc diseases
- CNS disorders
- metabolic
