Adrenal Cortex Flashcards
Describe the structure of the adrenal cortex and the hormones produced
Zona Glomerulosa - round cells - aldosterone - few lipid droplets
Zona Fasiculata - bundles of cells - glucocorticoids - lots of lipid
Zona Reticularis - nets of cells - adrenal androgens - few lipid droplets
What are the sources of free cholesterol in the body?
Acetate synthesis - little
Circulating lipoproteins - moderate
Synthesis from cholesterol esters from within the cell - main
Outline the enzyme pathways involved in cholesterol production.
Hydroxymethylglutaryl CoA reductase (HMG - CoA reductase) - sythesises cholesterol from acetate
Cholesterol ester hydrolase (CEH) (hormone sensitive lipase) - hydrolyses cholesterol esters from LDLs/HDLs and intracellular stores
acyl-CoA: cholesterol acyl transferase (ACAT) - responsible for synthesis of cholesterol esters from cholesterol
What is the role of StAR?
It shuttles cholesterol to the mitochondrial membrane.
Is it the only protein involved in this process?
No - StAR mutants still have some steroid synthesis which indicates a role for translocator protein or TSPO.
What might cells deficient in StAR look like?
They would have an accumulation of lipid droplets as there would be no negative feedback on the pituitary by steroid hormones. The pituitary would continue to produce trophic hormones that result in phosphorylation of CEH through protein kinases.
What does P450scc do?
This is a side chain cleavage enzyme that is present on the inner mitochondial membrane. The first stage in steroid synthesis of cholesterol to pregnenolone.
What chemicals increase/decrease aldosterone secretion?
INCREASE
ACTH
low K
ANG II - by blocking outward potassium channels
DECREASE
ANP
What is the mechanism of release?
Influx of calcium. Hence why low K leads to influx of Ca.
What are its actions?
Increase renal sodium retention and potassium secretion
Water conservation
Other than causing increase aldosterone secretion, how does intracellular calcium regulate aldosterone levels?
It increases mitochondrial activity, delivery of cholesterol to the outer mitochondrial membrane, increases cholesterol ester hydrolase activity and increases StAR transcription.
Is ACTH important for zona glomerulosa cells?
It is not thought to be. Hypophysectomy seems to have little effect on ZG size compared to its effects on the ZF.
What does ACTH do to the ZF and ZR?
Increase glandular blood flow, improving lipoprotein delivery.
Stimulation of steroid synthesis.
Depletion of ascorbic acid
What are the chronic effects of ACTH?
Increased adrenal weight, cell size and number
Increased steroid enzyme synthesis & therefore steroids
What is its pattern of secretion?
It has a diurnal pattern of secretion
What type of receptor does it act through?
G alpha stimulatory
On which gene is it encoded?
POMC gene
What receptor does ACTH act on and describe how it can be affected by other proteins in contrast to other receptors of the same type?
MCR2 receptor. Melanocortin receptor adapter proteins (MRAPs) seem to enhance shuttling of the receptor to the cell membrane from the ER. However, the effect of MRAPs is the opposite on other MCRs.
Other than ACTH, is there another hormone that may stimulate DHEA production?
Possibly prolactin
What is the cause and general features of Cushings?
Disease caused by chronic overexposure to glucocorticoids. This can be iatrogenic as well as due to excess endogenous GC production.
Varying signs and symptoms including fat deposition in certain areas, ammenhorrhea in women, decreased male fertility. (this is because GCs block the GnRH-R)
How does GC action vary between muscle and liver?
Anabolic in the liver and catabolic in muscle.
What are the reasons for increased GC production?
NOT causing cushings:
- stress
- pregnancy (late stage)
- athletes
- depression, alcoholism, malnutrition, anxiety
CAUSING cushings
- pituitary adenomas
- adrenal adenomas
- ectopic ACTH production
What do adrenal adenomas normally not produce?
Aldosterone
How could a pituitary adenoma/adrenal adenoma be distiguished grossly?
Pit - diffuse hyperplasia
Adrenal - nodular hyperplasia
