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This investigation was undertaken to determine the role of pituitary function and, in particular, the possible influence of growth hormone (GH) on hepatic low density lipoprotein (LDL)-receptor expression in response to dietary cholesterol. Feeding normal rats with 2% cholesterol for 5 or 6 days did not alter LDL-receptor numbers, LDL-receptor mRNA levels, or plasma cholesterol, although hepatic cholesterol increased 5-fold. When hypophysectomized rats received the same diet, the LDL-receptor number and its mRNA levels were reduced by 75%, plasma cholesterol increased 6-fold, and hepatic cholesterol increased 12-fold. Stepwise hormonal substitution of cholesterol-fed, hypophysectomized rats revealed that substitution with GH was important to restore hepatic LDL-receptor number and mRNA levels. The presence of GH was also important to reduce the hypercholesterolemia in cholesterol-fed hypophysectomized rats. We conclude that the presence of GH is important for hepatic LDL-receptor expression, both at the protein and the mRNA level. The resistance to suppression of rat hepatic LDL receptors by dietary cholesterol depends, at least in part, on the presence of GH.

proceedings of the national academy of sciences of the united states of america

Loss of resistance to dietary cholesterol in the rat after hypophysectomy: importance of the presence of growth hormone for hepatic low density lipoprotein-receptor expression.