regulation of adrenocortical steroidogenesis W6 Flashcards
cholesterol structure?
HO group (polar head group)
steroid body (4 rings)
hydrophobic side-chain
cholesterol as a component of cell membranes?
aligns between membrane phospholipids
attracted to polar head and hydrophobic tail
what are steroids soluble in
steroids are fat soluble
2 main types of steroid hormones? where are they made?
corticosteroids (cortex of adrenal gland)
sex steroids (made in gonads)
types of corticosteroids?sa
mineralocorticoids
glucocorticoids
adrenal androgens
mineralocorticoids function?
salt and water retention
glucocorticoids function
glucose synthesis
protein and lipid metabolism
inflammation, immune response
adrenal androgens function?
fetal steroids and growth
3 types of sex steroids?
androgens
oestrogens
progesterones
what is vitamin D?
steroid hormone
key adrenal steroid hormones? structural differences?
aldosterone (O, CH, OH)
cortisol (OH)
androstenedione (O)
what distinguishes a glucocorticoid from other steroids?
11 beta hydroxylase group (?)
steroid hormones mechanism of action (classic ‘genomic’)
circulating steroid hormones bind to hormone receptors in cytoplasm, makes active transcription complex that acts on DNA in nucleus creating mRNA that causes protein synthesis in cytoplasm
how long do steroid hormones take to act?
30 mins - 48 hrs
‘non-genomic’ mechanism of steroid hormones?
receptors such as ion channels in plasma membrane activated directly by steroid binding
‘non-genomic’ mechanism of steroid hormones time to act?
<1m
how are steroid hormones made from cholesterol?
hydrophobic 6 carbon side chain removed
varied substituent at C-17
Extra specificity from side chain modification eg C-11
2 types of enzymes involved in steroid synthesis?
cytochrome P450s (CYPs)
steroid dehydrogenases/reductases
where are cytochrome P450s highly expressed?
liver (drug detoxification)
organs that synthesize steroids (adrenal cortex, testis, ovary, placenta)
function of cytochrome P450s?
cleave or modify cholesterol side groups
function of steroid dehydrogenases/reductases?
interconvert active and inactive forms of steroid
cortisol inactive form?
cortisone
what steroid dehydrogenase/reductase converts cortisol to cortisone and vice versa?
11β-HSD1 and 11β-HSD2
cortisol pathways?
released from adrenal gland into circulation, 90%+ binds to transport protein and affects target tissues.
some cortisol recycles through liver, converted to cortisone which circulates and reaches target tissues where it is reactivated by 11β-HSD1
what do the adrenal glands do!
coordinates the bodies response to internal physiology and environmental stimuli
where are the adrenal glands located?
around 12th thoracic vertebra
positioned bilaterally and anteriorly above kidneys
anatomists name for adrenal glands?
suprarenal glands
2 endocrine axes that adrenal glands play a role in?
hypothalamic-pituitary-adrenal (HPA) axis
neuroendocrine sympathetic nervous system
which part of the adrenal glands is involved in the HPA axis
adrenal cortex
which part of the adrenal glands is involved in the neuroendocrine sympathetic nervous system
adrenal medulla
function of adrenal cortex?
makes steroid hormones
adrenal medulla function?
extension of sympathetic nervous system
makes catecholamines
blood supply to adrenal cortex?
short arteries penetrate the capsule, supply a subcapsular plexus of arterioles
capillary sinusoids extend through the cortex separating chords of cells
this structure allows rapid transmission of stimuli to cells and products to targets
adrenal medulla blood supply?
receives long cortical arteries and capillaries from cortex
adrenal medulla and cortex venous drainage?
drain via central and medullary vein
zones of adrenal cortex?
zone glomerulosa
zona fasciculata
zona reticularis
where is aldosterone made
zona glomerulosa
what is aldosterone under control of
RAS (renin-angiotensin system)
what does aldosterone regulate
salt and water retention in kidney distal tubule
aldosterone is the principle what?
aldosterone is the principle mineralocorticoid in humans
cortisol is the principle what?
cortisol is the principle glucocorticoid in humans
where is cortisol made
zona fasciculata
what is cortisol under control of
HPA axis
what does cortisol regulate?
glucose homeostasis
stress response
inflammation
immune response
where are C19 adrenal androgens made
zona reticularis
what are C19 adrenal androgens under control of
HPA axis
C19 adrenal androgens function?
intracrine conversion to testosterone and oestradiol in peripheral tissues
prenatal and postnatal DHEA production
positive regulators of CRH (cortisol releasing hormone)
serotonin
acetylcholine
encephalin
negative regulators of CRH (cortisol releasing hormone)
alpha-adrenergic agonists
GABA, endorphin
dopamine
circadian rhythm of CRH release?
CRH high in early morning (4-8) and lower later in day
CRH regulates ACTH release
ACTH high on waking (6-10) and lowest in middle of night
what are corticotropes
cells in anterior pituitary that release ACTH, MSH and lipotropin
homeostatic feedback regulation of cortisol synthesis by the HPA axis?
circadian rhythm and stress inputs stimulate CRH release from hypothalamus
CRH stimulates ACTH production from pituitary corticotrophs
ACTH stimulates cortisol production from adrenal zona fasciculata
cortisol feeds back on release of CRH from hypothalamus and ACTH from the anterior pituitary
StAR protein function?
steroid acute regulatory protein
sits in membrane of mitochondria and promotes transport of cholesterol from cytoplasm into mitochondria where steroid hormones are made
crucial regulatory step!!
what hormone levels rise as plasma glucose falls?
glucagon
adrenaline
noradrenaline
growth hormone
cortisol
dual action of cortisol?
anabolic in liver to promote gluconeogenesis
catabolic in peripheral muscle and fat to promote protein and lipid breakdown
anabolic actions of cortisol?
increased gluconeogenesis and liver glucose output
catabolic actions of cortisol?
inhibition of glucose uptake by peripheral muscle fat and tissue
immune system suppression
increased muscle protein breakdown
increased fat breakdown
increased bone resorption
increased appetite and central fat deposition
pathophysiological actions of cortisol - anabolic?
elevated plasma glucose - secondary diabetes mellitus
pathophysiological actions of cortisol - catabolic?
muscle and connective tissue wasting and weakness
poor wound healing and skin ulcers
uncontrolled muscle protein breakdown
increased fat redistribution
osteoporosis
uncontrolled appetite and central fat deposition
excess mineralocorticoid action = Na+ and fluid retention and hypertension
disease of cortisol excess?
Cushing’s Disease
Cushing’s disease - features
hypertension
low plasma K+
elevated plasma cortisol
low plasma aldosterone and renin activity.
