Cholesterol and lipoprotein metabolism in aging - Reversal of hypercholesterolemia by growth hormone treatment in old rats
Cholesterol and lipoprotein metabolism in aging - Reversal of hypercholesterolemia by growth hormone treatment in old rats
复制标题
DOI：
10.1161/01.atv.19.4.832
复制
发表时间：
1999-04-01
影响因子：
8.7
通讯作者：
Rudling, M
中科院分区：
文献类型：
--
作者：
Parini, P;Angelin, B;Rudling, M
血浆胆固醇水平随着年龄的增长而增加，冠心病的发病率也是如此。与年龄相关的高胆固醇血症的机制还不清楚。一个有趣的假设表明，生长激素（GH）的相对缺乏，这与衰老发生，有助于与年龄相关的高胆固醇血症的发展，因为GH对胆固醇代谢有有益的影响。在目前的工作中，我们测试了这一假设的行政GH正常大鼠的不同年龄。在2月龄、12月龄和1月龄雄性Sprague-Dawley大鼠中表征血浆脂质和肝脏胆固醇代谢。在2月龄大鼠中，GH以剂量依赖的方式特异性地刺激肝脏低密度脂蛋白（LDL）受体的表达，无论是在蛋白水平还是在mRNA水平。同时，大的高密度脂蛋白和LDL组分中的血浆胆固醇增加约30%。在12个月大的动物中，胆固醇7 α-羟化酶（C7 α OH）活性降低，而肝脏LDL受体和血浆总胆固醇不变。GH治疗（1 mg kg（-1）d（-1））使C7 α OH的活性正常化，对血浆胆固醇和LDL受体的影响与2个月大的动物相似。在18个月大的大鼠中，血浆胆固醇增加2倍，而肝脏LDL受体表达和C7 α OH活性与12个月大的动物相似。向18月龄大鼠输注CH对肝脏C7 α OH和LDL受体的影响与12月龄大鼠相似。然而，GH治疗强烈降低了18月龄动物的高胆固醇血症。我们的结论是，大鼠血浆胆固醇的年龄依赖性增加可以逆转GH的管理，大概是通过这种激素对脂蛋白代谢的多效性作用。
Plasma cholesterol levels increase with age, as does the incidence of coronary heart disease. The mechanisms responsible for the age-related hypercholesterolemia are not well understood. An interesting hypothesis suggests that the relative deficiency in growth hormone (GH), which occurs with aging, contributes to the development of the age-related hypercholesterolemia, because GH has beneficial effects on cholesterol metabolism. In the present work, we tested this hypothesis by the administration of GH to normal rats of varying ages. Plasma lipids and hepatic cholesterol metabolism were characterized in 2-, 12-, and Is-month-old male Sprague-Dawley rats. In 2-month-old rats, GH specifically stimulated the hepatic low density lipoprotein (LDL) receptor expression in a dose-dependent way, both at the protein level and at the mRNA level. Concomitantly, plasma cholesterol increased by approximate to 30% within the large high density lipoprotein and LDL fractions. In 12-month-old animals, cholesterol 7 alpha-hydroxylase (C7 alpha OH) activity was reduced, whereas hepatic LDL receptors and plasma total cholesterol were unchanged. GH treatment (1 mg kg(-1) d(-1)) normalized the activity of C7 alpha OH and had effects on plasma cholesterol and LDL receptors similar to these seen In 2-month-old animals. In 18-month-old rats, plasma cholesterol was increased 2-fold, whereas hepatic LDL receptor expression and C7 alpha OH activity were similar to those of the 12-month-old animals. Infusion of CH to 18-month-old rats had similar effects on hepatic C7 alpha OH and LDL receptors as seen in 12-month-old rats. However, GH treatment strongly reduced the hypercholesterolemia in 18-month-old animals. We conclude that the age-dependent increase of plasma cholesterol in rats can be reversed by the administration of GH, presumably through the pleiotropic effects of this hormone on Lipoprotein metabolism.