Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice

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 ch olesterol 7 alpha -hydroxylase (C7 alpha OH), and for the maintenance of re sistance to dietary cholesterol. The present study aimed to determine wheth er GH has beneficial effects on plasma lipids and hepatic cholesterol metab olism in mice devoid of LDLR. Compared with wild-type controls, LDLR-defici ent mice had similar to 250% elevated plasma total cholesterol and similar to 50% increased hepatic cholesterol levels; hepatic HMG CoA reductase acti vity was reduced by 70%, whereas C7 alpha OH activity was increased by 40%. In LDLR mice, GH infusion reduced plasma cholesterol and triglycerides up to 40%, whereas HMG CoA reductase and C7 alpha OH activities were stimulate d by similar to 50% and 110% respectively. GH also stimulated HMG CoA reduc tase and C7 alpha OH activities in control mice, whereas hepatic LDLR and p lasma lipoproteins were unchanged. The effects of cholestyramine and atorva statin on C7 alpha OH in LDLR-deficient mice were potentiated by GH, and th is was associated with a further reduction in plasma cholesterol. GH treatm ent reduces plasma cholesterol and triglycerides and stimulates C7 alpha OH 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.