© 1999 American Heart Association, Inc.
Original Contributions |
Cholesterol and Lipoprotein Metabolism in Aging
Reversal of Hypercholesterolemia by Growth Hormone Treatment in Old Rats
From the Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine, and the Molecular Nutrition Unit, Center for Nutrition and Toxicology, Novum, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
Correspondence to Mats Rudling, MD, PhD, CME, M63, Huddinge University Hospital, S-141 86 Huddinge, Sweden. E-mail mats.rudling{at}cnt.ki.se
Abstract—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 18-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 
30% within the large high
density lipoprotein and LDL fractions. In 12-month-old animals,
cholesterol 7
-hydroxylase (C7OH) 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
C7OH and had effects on plasma cholesterol and LDL
receptors similar to those seen in 2-month-old animals. In 18-month-old
rats, plasma cholesterol was increased 2-fold, whereas
hepatic LDL receptor expression and C7OH activity were similar to
those of the 12-month-old animals. Infusion of GH to 18-month-old rats
had similar effects on hepatic C7OH 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.
Key Words: aging • cholesterol • cholesterol 7-hydroxylase • growth hormone • LDL receptor
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