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Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice

Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine, and Molecular Nutrition Unit, Center for Nutrition and Toxicology, Novum, Karolinska Institute at Huddinge University Hospital, S-141 86, Stockholm, Sweden

¹Correspondence: CME, M63, Huddinge University Hospital, S-141 86 Stockholm, Sweden. E-mail: mats.rudling{at}cnt.ki.se

Growth hormone (GH) has pleiotropic effects on cholesterol and lipoprotein metabolism. Pituitary GH is important for the normal regulation of hepatic LDL receptors (LDLR), for the enzymatic activity of bile acid regulatory cholesterol 7-hydroxylase (C7OH), and for the maintenance of resistance to dietary cholesterol. The present study aimed to determine whether GH has beneficial effects on plasma lipids and hepatic cholesterol metabolism in mice devoid of LDLR. Compared with wild-type controls, LDLR-deficient mice had 250% elevated plasma total cholesterol and 50% increased hepatic cholesterol levels; hepatic HMG CoA reductase activity was reduced by 70%, whereas C7OH activity was increased by 40%. In LDLR mice, GH infusion reduced plasma cholesterol and triglycerides up to 40%, whereas HMG CoA reductase and C7OH activities were stimulated by 50% and 110% respectively. GH also stimulated HMG CoA reductase and C7OH activities in control mice, whereas hepatic LDLR and plasma lipoproteins were unchanged. The effects of cholestyramine and atorvastatin on C7OH in LDLR-deficient mice were potentiated by GH, and this was associated with a further reduction in plasma cholesterol. GH treatment reduces plasma cholesterol and triglycerides and stimulates C7OH activity in mice devoid of LDLR, particularly in combination with resin or statin treatment. The potential of GH therapy in patients with homozygous familial hypercholesterolemia should be evaluated.—Rudling, M., Angelin, B. Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice.

Key Words: hypercholesterolemia • familial • cholesterol 7-monooxygenase • statins • resins

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