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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 (C7
OH), 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
C7
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
OH activities were stimulated by
50%
and 110% respectively. GH also stimulated HMG CoA reductase and
C7
OH activities in control mice, whereas hepatic LDLR and plasma
lipoproteins were unchanged. The effects of cholestyramine and
atorvastatin on C7
OH 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 C7
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.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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