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Growth hormone reduces plasma cholesterol in LDL receptor‐deficient mice
Author(s) -
Rudling Mats,
Angelin Bo
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0715com
Subject(s) - endocrinology , medicine , ldl receptor , cholesterol , hmg coa reductase , cholestyramine , chemistry , reductase , atorvastatin , reverse cholesterol transport , hormone , lipoprotein , biology , enzyme , biochemistry
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 7α‐hydroxylase (C7αOH), 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 de‐void 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 re¬duced by 70%, whereas C7αOH activity was increased by 40%. In LDLR mice, GH infusion reduced plasma cholesterol and triglycerides up to 40%, whereas HMG CoA reductase and C7αOH activities were stimulated by ~ 50% and 110% respectively. GH also stimulated HMG CoA reductase and C7aOH activities in control mice, whereas hepatic LDLR and plasma lipoproteins were unchanged. The effects of cholestyramine and atorvastatin on C7αOH 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 stim¬ulates C7αOH activity in mice devoid of LDLR, partic¬ularly in combination with resin or statin treatment. The potential of GH therapy in patients with homozygous familial hypercholesterolemia should be evalu¬ated.—Rudling, M., Angelin, B. Growth hormone reduces plasma cholesterol in LDL receptor‐deficient mice. FASEB J. 15, 1350–1356 (2001)