Steroid Biosynthesis

Question 1

What is the precursor for all steroids?

Answer 1

Cholesterol or cholesterol esters derived from lipid uptake from GI or liver synthesis. They are transported in the blood as various micellar proteins called apolipoprotiens

Question 2

Describe the synthesis of cholesterol in the liver and then endogenous metabolism of cholesterol.

Answer 2

Begins with Acetyl CoA, which is converted to HMG-CoA and then to mevalonate by HMG-CoA reductase (rate limiting stage). Mevalonate is then converted into cholesterol. Cholesterol sends negative feedback inhibition to HMG-CoA reductase.

• Cholesterol released, broken down by LPL causing depletion of triacylglycerol which trigger rearrangement of proteins.
• Cholesterol-ester transfer protein adds cholesterol esters from HDL to VLDL, IDL and LDL.

Question 3

How is cholesterol transported around the body?

Answer 3

HDL, IDL and LDL. In particular LDL which contains high concs of cholesterol, are responsible for transport and cellular uptake via receptor mediated endocytosis of cholesterol into steroidogenic cells

Question 4

Describe the classification of plasma lipoproteins

Answer 4

• Based on lipoprotein amount and size,
• Chylomicron which are the largest.
• Then VLDL, IDL, LDL, HDL (decreasing in size but increasing in density) All stem from LDL. HDL is made by liver. VLDV gets altered into different particles

Question 5

Describe the exogenous pathway of cholesterol metabolism

Answer 5

• Gut absorbs all fat, the epithelial cells make chylomicrons.
• The chylomicrons are broken down by lipoprotein lipases into free fatty acids and glycerol (taken up by tissues or adipocytes - Adipocytes resynthesise TAG and stores it as fats. Remnant chylomicrons then endocytosed by liver. Liver makes VLDLs from remnant chylomicrons and cholesterol.

Question 6

Describe what must occur to cholesterol carried HDL?

Answer 6

It must be esterified by LCAT before it can be transferred to other molecules for use in the body

Question 7

describe the uptake of cholesterol by cells which synthesis steroids

Answer 7

LDL binds to surface LDL receptor via the Apo-B-100 protein. The endocytosis of the LDL is mediated by a clathrin coat.
Depolymerisation of clathrin allows the vesicle carry LDL to fuse with lysosomes. This breaks it down into amino acids, cholesterol and FFA. The cholesterol can then be used do produce Pregnenolone (precursor for all steroids)

Question 8

What are the main physiological roles of cholesterol?

Answer 8

• Forms component of cell membrane (decreases membrane fluidity, decreases physical permeability),
• Precursor for production of bile salts
• Precursor for all steroid hormones

Question 9

Describe how cholesterol esters are turn unto steroid hormones

Answer 9

• Cholesterol esters hydrolysed by chol. ester hydrolase to form cholesterol.
• Cholesterol is then catalysed by desmolase to form pregnenolone.
• Pregnenolone is then converted via a range of enzymes (Cyt P450) into different enzymes; Progesterone, testosterone (can from oestradiol), cortisol and aldosterone.

Question 10

Describe the anatomy of the adrenal gland

Answer 10

• Cortex which has three layers; Outermost = Glomerulosa which secrete aldosterone and then the inner two layers (fasciculata and reticularis) synthesis cortisol and sex steroids.
• Medulla which contains chromaffin cells that secrete adrenaline and noradrenaline

Question 11

What is the function of Leydig cells and Sertoli cells

Answer 11

Leydig cells produce testosterone which is processed peripherally into the more active androgen dihydro-testosterone (DHT). Both are required for the neighbouring Sertoli cells which regulate sperm maturation. Sertoli cells also convert some testosterone to oestradiol

Question 12

What is the function of thecal and granulosa cells?

Answer 12

They work in synergy to produce the oestrogens and progestins which exhibit specific release profiles over the duration of the menstrual cycle