The insulin or thyroid hormones increases HMG-CoA reductase activity and ultimately cholesterol biosynthesis. Increase in insulin or thyroxine favours upregulation of the expression of the gene for HMG-CoA reductase. Glucagon and glucocorticoids have opposite effects. Insulin decreases cAMP levels by increasing protein phsophatase activity. The dephosphorylated HMG-CoA reductase is active and increase cholesterol biosynthesis. The influx of Cholesterol into cells inhibits the transcription of genes encoding HMG-CoA synthase, HMG-CoA reductase and other enzymes of cholesterol biosynthesis, as well as the LDL receptor itself.
Many individuals suffering from obesity or diabetes caused by Insulin resistance have fatty livers, which in some cases leads to liver failure. Fatty livers due to insulin resiatance is caused by elevated levels of SREBP in response to elevated insulin levels. Hyperthyroidism causes the same effect?? How thyroid hormones act on cholesterol biosynthesis enzymes?? And how hypothyroidism and hyperthyroidism at the same time causes elevated cholesterol levels??
The primary mechanism for hypercholesterolemia in hypothyroidism is accumulation of LDL cholesterol due to a reduction in the number of cell surface receptors for LDL, resulting in decreased catabolism of LDL. Other mechanisms also may affect the serum cholesterol concentration in hypothyroidism:
LDL oxidation is significantly increased in hypothyroid patients, the degree of which is directly related to the serum LDL cholesterol concentration. Diminished secretion of cholesterol into bile has been demonstrated in hypothyroid rats. Reduced cholesteryl ester transfer (the net transfer of cholesterol from HDL to LDL and very-low-density-lipoprotein [VLDL]) in hypothyroidism may minimize the increase in serum LDL cholesterol concentrations.
A different mechanism, reduced lipoprotein lipase activity, is responsible for the development of hypertriglyceridemia in hypothyroidism. The rate of synthesis of triglycerides is normal.
The mechanism for hypocholesterolemia in hyperthyroidism is increase fatty acid clearance, but lipolysis is increased even more, resulting in high serum fatty acid concentrations.
But if cellular cholesterol levels are low then biosynthesis will be enhanced by mechanisms involving SERBP. Thyroxine is positive regulator of cholesterol biosynthesis then how reduced thyroid hormone levels cause hypercholesterolemia or increased thyroid hormone levels cause hypocholesterolemia
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