Biosynthesis and action Flashcards
what are adrenal steroid hormones synthesised from
cholesterol
What are the 2 sources of cholesterol. The main one?
cell stores - acetyl-CoA
mainly derived from plasma LDL
What’s the rate-limiting step of steroidogenesis?
transport of cholesterol from the outer to the inner mitochondrial membrane
Where is the first enzyme of steroidogenesis located?
inner mitochondrial membrane - initial side-chain cleavage of cholesterol
What is cholesterol turned into?
What enzyme?**
What happens?
pregnenolone
enzyme = A = cholesterol 20,22 desmolase
made into pregnenolone to start zone specific steroid hormone synthesis
What are the 3 parts of the cortex?
zona glomerulosa
zona fasciculata
zona reticularis
What are the cells found in the medulla and what do they secrete?
chromatin cells
secrete - adrenaline, noradrenaline, dopamine, enkephalins and somatostatin
What’s the main mineralocorticoid?
aldosterone
Where is aldosterone made? Why is this place the only place that can make it?
made in zona glomerulosa
only one to contain aldosterone synthase enzyme
What’s the pathway for aldosterone production?
mineralcorticoid pathway
What is the main glucocorticoid?
cortisol (hydrocortisol)
What enzyme is lacking in the zona glomerulosa?
enzyme F
What 2 things are made at the zona reticularis? Why is it only made here?
DHEA and androstenedione (weak androgens)
zona fasciculata lacks cofactors for F* enzyme
Broadly speaking, what do mineralocorticoids and glucocorticoids do?
Na+ retention
anti-inflammatory
what’s the only hormone that regulates the HPA axis? What’s the consequence of this?
CORTISOL
excess levels of aldosterone and androgens can’t turn the system off
what does aldosterone do? What stimulates its secretion?
act on DCT and CD to promote Na+ retention (water retention) and K+ elimination
stimulated by increased plasma [K+] and RAA (dependent on ACTH)
What do the weak androgens do in females and males? What is it regulated by?
females - axillary and public hair growth, libido
neglible in men
regulated by ACTH (but cause no feedback)
What can long term use of glucocorticoids cause?
down-regulate ACTH causing adrenal gland atrophy and Cushing’s disease
What can dehydration trigger?
release of AVP (ADH) which stimulates ACTH
CRH and AVP are synergistic – T/F?
TRUE - to elevate ACTH
what is the role of the SCN in regulation of cortisol?
controls endogenous circadian rhythm
influences the hypothalamus which regulates cortisol further down the axis
What’s the overall metabolic activity of cortisol? Go over the fine details
Metabolic effects
muscle and adipose- catabolic
liver- stimulate gluconeogenesis and glycogen storage
to elevate plasma glucose levels
What does cortisol also do about glycogen?
build up glycogen stores
Explain cortisol’s anti-inflammatory effects and immunosupressive effects– under what conditions?
At high physiological levels
- production of lipocortin 1 (inhibits PLA2)
- decrease T-lymphocytes
- decrease cytokines
- stabilises lysosomes
- decrease NO production
