Corticosteroid Prodcution Flashcards
What are steroid hormones derivative of?
Enzymatic modification of cholesterol
Which enzymes regulate steriodogenesis?
The ones that convert cholesterol into the steroid hormone of interest
Where are the enzymes that convert cholesterol to steroid hormones located?
Mitochondria
Smooth ER
What is the typical feature of a steroid hormone?
A ring structure
Steroid hormones are lipid soluble, what does this mean?
They are freely permeable to membranes
They aren’t stored, but immediately released after synthesis
Have to be carried in the blood complexed to specific binding globulins
Which binding globulin carrier cortisol?
Corticosteroid binding globulin
Why are the adrenal glands yellow?
High concentration of cholesterol
What is the arterial supply of the adrenal glands
Superior, middle and inferior suprarenal arteries
- centrepetal blood flow supplies all the layers
What’s the venous drainage of the adrenal gland?
Arterial blood starts at the outer surface of the gland, and trickles down into the medullary vein
The veins emerge from the hilum of each gland and join to become the suprarenal vein
Suprarenal veins join the IVC (on the right) and the left renal vein (on the left)
What is the nervous supply of the adrenal glands?
Nerves derived from the coeliac plexus and thoracic splanchnic nerves
Nerves supply the chromaffin cells of the adrenal medulla
Describe the layers within the adrenal gland.
Fibrous capsule
Zona glomerulosa - clusters of small cells, fewer lipids
Zona fasciculata - large cells arranged in cords
Zone reticularis - smaller cells in a haphazard arrangement
Medulla - chromaffin cells and numerous capillaries
What does each layer of the adrenal gland produce?
Zona glomerulosa - mineralocorticoids
Zona fasciculata - glucocorticoids
Zona reticularis - androgens
Medulla - catecholamines
Give two examples of mineralocorticoids, their action and regulation.
Aldosterone, deoxycorticosterone
Regulated by the RAS system
These control blood pressure and sodium homeostasis
Give two examples of glucocorticoids, regulation and function.
Cortisol, corticosterone
Regulated by ACTH
Helps to regulate carbohydrates
Give two examples of androgens, regulation and function.
DHEA, androstenedione
Regulated by ACTH
Important source of androgens in women
- testosterone in the testes is much more active in men
Sources of cholesterol
Taken up from circulation
Synthesised de novo from acetyl-CoA
What is the rate limiting step of cholesterol biosynthesis
HMG-CoA reductase
How does cholesterol enter the cell from the circulation?
LDL complex is taken into cells via LDL receptors
Broken down into esterified cholesterol and then free cholesterol
What is the first enzymatic step in the creation of steroid hormones?
Conversion of cholesterol to pregnenolone - by cleaving a side chain of the cholesterol
Where is the enzyme that catalyses the cholesterol to pregnenolone reaction located, and what is it?
Cytochrome P450 (with cofactor) Located in the inner mitochondrial membrane
What it the rate limiting step in the cholesterol to pregnenolone reaction?
The transport of free cholesterol from the cytoplasm to the mitochondria
Which protein moves cholesterol from the cytoplasm into the mitochondria?
Steroidogenic acute regulatory protein - StAR