Adrenals and corticosteroids Flashcards
where are the adrenal glands
above the kidneys
layout of the adrenal gland
inside = medulla
outside = cortex
anything from cortex has to drain through medulla into tributary of central vein
describe the blood vessels of the adrenal glands
L adrenal gland vein - renal vein - vena cave
R - vena cava
one vein to secrete hormones into the blood
both have many arteries though - to supply the kidney’s with the blood that they need
parts of the cortex from outside in and the hormones they make
tough, fibrous capsule
zona glomerulosa - aldosterone (mineralocorticoids)
zona fasciculata and zona reticularis - cortisol (glucocorticoids)
cortex also make sex steroids - androgens and oestrogens
what hormones does the medulla make
catecholamines
- adrenaline, noradrenaline
describe the synthesis of steroid hormones
all from cholesterol
mineralocorticoids and glucocorticoids - C21. in sex hormones more is cleaved off the backbone
lipoprotein deliver cholesterol
fat droplets in esters
signal cause esterase to relieve cholesterol from esters
StAR protein takes cholesterol into the mitochondria
the enzymes to make the hormone are different in different parts of the cortex
difference in the pathway of aldosterone and cortisol production
in aldosterone production 1 enzyme is removed making progesterone
1 enzyme is added making aldosterone from corticosterone which is inactive on its own
why are there only a few sex steroids
the enzymes for their synthesis are extra so are at low levels
describe the storage of steroid hormones
lipid soluble - don’t stay in cell long
protein store for hormone
albumin/CBG (corticosteroid binding globulin)
90% of cortisol is protein bound, 60% of aldosterone is protein bound
effect of hormones being relieved from proteins
if high proportion of the protein is bound - small decrease in binding has a large effect
what are the concentrations of the steroid hormones
cortisol level is diurnal - change throughout the day and 1000x higher than aldosterone always
corticosteroid receptors
glucocorticoid receptors (GR) aldosterone receptors (MR)
which receptor does aldosterone use
MR
which receptor does cortisol use
GR and MR
not specific
what makes aldosterone useful if it is in such low qunatities and only has 1 receptor
the enzyme 11b-hydoxysteroid dehydrogenase 2 is a cortisol metabolising enzyme - break cortisol into cortisone - inactive
kidney and placenta (stop maternal cortisol getting at foetus) protected from cortisol so still need aldosterone
what increases renin production
low Na conc
renal perfusion pressure decrease
increase in renal sympathetic activity
where is renin produced
granular cells in kidney
describe how the renin-angiotensin system is linked to aldosterone secretion
macular densa cells sense Na drop in fluid in kidney
stimulates renin production
Increases Na reabsorbtion and so water - maintains Bp (low Bp shown by low RPP)
renin is enzyme number 1, activates angiotensinogen to angiotensin 1
lung have a lot of angiotensin converting enzyme (ACE) – angiotensin II
stimulates production of aldosterone in adrenalcortico gland
other stimuli for aldosterone synthesis
increased K+
decreased Na+
describe the stimulus of cortisol
hypothalamic hormone - corticotrophin releasing hormone - act on anterior pituitary gland corticotrophs
releases adrenocorticotropin (ACTH) act on adrenal cortex
cortison produced
how is cortisol production controlled
-ve feedback
what happens in the kidney
electrolytes are reabsorbed
describe the physiological effect of aldosterone
act in kidney
late distal tubule/collecting duct
Na is driven into DCT then into the blood
Na channel at lumen - Na enters by diffusion if concentration gradient
Na/K ATPase makes sure there is a conc gradient as Na is removed into the blood
some K is lost
aldosterone is slow acting, it increases the number of Na channels and ATPases ie it upregulates the ability to absorb Na
allows water to diffuse through DCT as it provides an osmotic gradient
describe the generic action of cortisol
it binds to the GR receptor and changes protein transcription and translation
why is the mechanism of cortisol complex
which receptor is relevant to which effect
there are optimal levels of activation
ideally it heavily binds to MR and partially binds to GR - activation
in times of stress there is acute GR activation - convert back to normal as quick as possible
describe cortisol’s effect on metabolism
makes sure that glucose is readily available and that glucose stores are full
in liver increases gluconeogenesis and
allow liver to generate glucose at max capacity
increase enzymes that allow glucose to be stored as glycogen
stop glucose being stored peripherally - inaccessible
reduce blood flow to tissues
stop glucose/fatty acid being stored in skeletal muscle/adipose tissue
the effect of this is maximal in sleep
describe cortisol and memory physiologically
promemory
imprint memory for survival
the dante gyrus in the hippocampus is where memories are produced serotonin promotes memory formation - promotes granule cell division
cortisol makes more serotonin 5HT 1A receptors
serotonin makes the hippocampus more sensitive to cortisol.
cortisol - positive effect on serotonin and serotonin upregulates the memory
describe cortisol’s action as an anti-inflammatory/immunosuppressive
homeostatic - turn of inflammatory response
released to dampen down inflammation
in supra-physiological actions cortisol not part of the feedback loop - continually
roduced
in stress cortisol constantly suppressing immune system - more susceptible to disease
what increases the cortisol levels
caffeine and alcohol
how does cortisol have supra-physiological actions for memory
if have chronically high cortisol
excessive GR activation - negative effect on serotonin
hippocampus gets smaller
inhibit the ability for long term memory formation
describe adrenal androgens
synthesised in zona reticularis
dehydroepiandrostenedione DHEAS and androstenedione
weak biological activity - converted to more active androgens eg testosterone by enzymes in peripheral tissue
women -adrenal production of DHEA and DHEA-S contributes substantially to overall androgen production and effects
men - the adrenal contribution to androgen is very small
if adrenal cortex is over active - enough sex hormone is produced to have an effect
