Abstract
This investigation was undertaken to determine the role of pituitary function and, in particular, the possible influence of growth hormone (GH) on hepatic low density lipoprotein (LDL)-receptor expression in response to dietary cholesterol. Feeding normal rats with 2% cholesterol for 5 or 6 days did not alter LDL-receptor numbers, LDL-receptor mRNA levels, or plasma cholesterol, although hepatic cholesterol increased 5-fold. When hypophysectomized rats received the same diet, the LDL-receptor number and its mRNA levels were reduced by 75%, plasma cholesterol increased 6-fold, and hepatic cholesterol increased 12-fold. Stepwise hormonal substitution of cholesterol-fed, hypophysectomized rats revealed that substitution with GH was important to restore hepatic LDL-receptor number and mRNA levels. The presence of GH was also important to reduce the hypercholesterolemia in cholesterol-fed hypophysectomized rats. We conclude that the presence of GH is important for hepatic LDL-receptor expression, both at the protein and the mRNA level. The resistance to suppression of rat hepatic LDL receptors by dietary cholesterol depends, at least in part, on the presence of GH.
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- Abbott R. D., Garrison R. J., Wilson P. W., Epstein F. H., Castelli W. P., Feinleib M., LaRue C. Joint distribution of lipoprotein cholesterol classes. The Framingham study. Arteriosclerosis. 1983 May-Jun;3(3):260–272. doi: 10.1161/01.atv.3.3.260. [DOI] [PubMed] [Google Scholar]
- Blackett P. R., Weech P. K., McConathy W. J., Fesmire J. D. Growth hormone in the regulation of hyperlipidemia. Metabolism. 1982 Feb;31(2):117–120. doi: 10.1016/0026-0495(82)90121-4. [DOI] [PubMed] [Google Scholar]
- Blankenhorn D. H., Nessim S. A., Johnson R. L., Sanmarco M. E., Azen S. P., Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987 Jun 19;257(23):3233–3240. [PubMed] [Google Scholar]
- Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
- Cohen B. I., Raicht R. F., Mosbach E. H. Sterol metabolism studies in the rat. Effects of primary bile acids (sodium taurochenodeoxycholate and sodium taurocholate) on sterol metabolism. J Lipid Res. 1977 Mar;18(2):223–231. [PubMed] [Google Scholar]
- Elam M. B., Simkevich C. P., Solomon S. S., Wilcox H. G., Heimberg M. Stimulation of in vitro triglyceride synthesis in the rat hepatocyte by growth hormone treatment in vivo. Endocrinology. 1988 Apr;122(4):1397–1402. doi: 10.1210/endo-122-4-1397. [DOI] [PubMed] [Google Scholar]
- Elam M. B., Wilcox H. G., Solomon S. S., Heimberg M. In vivo growth hormone treatment stimulates secretion of very low density lipoprotein by the isolated perfused rat liver. Endocrinology. 1992 Dec;131(6):2717–2722. doi: 10.1210/endo.131.6.1446613. [DOI] [PubMed] [Google Scholar]
- Ericsson S., Eriksson M., Vitols S., Einarsson K., Berglund L., Angelin B. Influence of age on the metabolism of plasma low density lipoproteins in healthy males. J Clin Invest. 1991 Feb;87(2):591–596. doi: 10.1172/JCI115034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frick M. H., Elo O., Haapa K., Heinonen O. P., Heinsalmi P., Helo P., Huttunen J. K., Kaitaniemi P., Koskinen P., Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987 Nov 12;317(20):1237–1245. doi: 10.1056/NEJM198711123172001. [DOI] [PubMed] [Google Scholar]
- Friedman M., Byers S. O., Elek S. R. Pituitary growth hormone essential for regulation of serum cholesterol. Nature. 1970 Jan 31;225(5231):464–467. doi: 10.1038/225464a0. [DOI] [PubMed] [Google Scholar]
- Goldstein J. L., Brown M. S. Regulation of the mevalonate pathway. Nature. 1990 Feb 1;343(6257):425–430. doi: 10.1038/343425a0. [DOI] [PubMed] [Google Scholar]
- Gordon T., Kannel W. B., Castelli W. P., Dawber T. R. Lipoproteins, cardiovascular disease, and death. The Framingham study. Arch Intern Med. 1981 Aug;141(9):1128–1131. [PubMed] [Google Scholar]
- Grundy S. M., Vega G. L., Bilheimer D. W. Kinetic mechanisms determining variability in low density lipoprotein levels and rise with age. Arteriosclerosis. 1985 Nov-Dec;5(6):623–630. doi: 10.1161/01.atv.5.6.623. [DOI] [PubMed] [Google Scholar]
- Heiss G., Tamir I., Davis C. E., Tyroler H. A., Rifkand B. M., Schonfeld G., Jacobs D., Frantz I. D., Jr Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation. 1980 Feb;61(2):302–315. doi: 10.1161/01.cir.61.2.302. [DOI] [PubMed] [Google Scholar]
- Henriksson P., Stamberger M., Eriksson M., Rudling M., Diczfalusy U., Berglund L., Angelin B. Oestrogen-induced changes in lipoprotein metabolism: role in prevention of atherosclerosis in the cholesterol-fed rabbit. Eur J Clin Invest. 1989 Aug;19(4):395–403. doi: 10.1111/j.1365-2362.1989.tb00248.x. [DOI] [PubMed] [Google Scholar]
- Hui D. Y., Innerarity T. L., Mahley R. W. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors. J Biol Chem. 1981 Jun 10;256(11):5646–5655. [PubMed] [Google Scholar]
- Ishibashi S., Murase T., Yamada N., Tanaka K., Takaku F., Sato K. Hyperlipidaemia in patients with hypopituitarism. Acta Endocrinol (Copenh) 1985 Dec;110(4):456–460. doi: 10.1530/acta.0.1100456. [DOI] [PubMed] [Google Scholar]
- Johnson R. J. Diminution of pulsatile growth hormone secretion in the domestic fowl (Gallus domesticus): evidence of sexual dimorphism. J Endocrinol. 1988 Oct;119(1):101–109. doi: 10.1677/joe.0.1190101. [DOI] [PubMed] [Google Scholar]
- Kovanen P. T., Brown M. S., Basu S. K., Bilheimer D. W., Goldstein J. L. Saturation and suppression of hepatic lipoprotein receptors: a mechanism for the hypercholesterolemia of cholesterol-fed rabbits. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1396–1400. doi: 10.1073/pnas.78.3.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Markussis V., Beshyah S. A., Fisher C., Sharp P., Nicolaides A. N., Johnston D. G. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet. 1992 Nov 14;340(8829):1188–1192. doi: 10.1016/0140-6736(92)92892-j. [DOI] [PubMed] [Google Scholar]
- Merimee T. J., Hollander W., Fineberg S. E. Studies of hyperlipidemia in the HGH-deficient state. Metabolism. 1972 Nov;21(11):1053–1061. doi: 10.1016/0026-0495(72)90036-4. [DOI] [PubMed] [Google Scholar]
- Oscarsson J., Olofsson S. O., Bondjers G., Edén S. Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins. Endocrinology. 1989 Sep;125(3):1638–1649. doi: 10.1210/endo-125-3-1638. [DOI] [PubMed] [Google Scholar]
- Oscarsson J., Olofsson S. O., Vikman K., Edén S. Growth hormone regulation of serum lipoproteins in the rat: different growth hormone regulatory principles for apolipoprotein (apo) B and the sexually dimorphic apo E concentrations. Metabolism. 1991 Nov;40(11):1191–1198. doi: 10.1016/0026-0495(91)90215-i. [DOI] [PubMed] [Google Scholar]
- Paigen B., Ishida B. Y., Verstuyft J., Winters R. B., Albee D. Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice. Arteriosclerosis. 1990 Mar-Apr;10(2):316–323. doi: 10.1161/01.atv.10.2.316. [DOI] [PubMed] [Google Scholar]
- Paigen B., Morrow A., Brandon C., Mitchell D., Holmes P. Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis. 1985 Oct;57(1):65–73. doi: 10.1016/0021-9150(85)90138-8. [DOI] [PubMed] [Google Scholar]
- Rosén T., Bengtsson B. A. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4;336(8710):285–288. doi: 10.1016/0140-6736(90)91812-o. [DOI] [PubMed] [Google Scholar]
- Rudling M., Angelin B. Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo. J Clin Invest. 1993 Jun;91(6):2796–2805. doi: 10.1172/JCI116522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudling M. Hepatic mRNA levels for the LDL receptor and HMG-CoA reductase show coordinate regulation in vivo. J Lipid Res. 1992 Apr;33(4):493–501. [PubMed] [Google Scholar]
- Rudling M., Norstedt G., Olivecrona H., Reihnér E., Gustafsson J. A., Angelin B. Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6983–6987. doi: 10.1073/pnas.89.15.6983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudman D., Feller A. G., Nagraj H. S., Gergans G. A., Lalitha P. Y., Goldberg A. F., Schlenker R. A., Cohn L., Rudman I. W., Mattson D. E. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1–6. doi: 10.1056/NEJM199007053230101. [DOI] [PubMed] [Google Scholar]
- Rudman D., Kutner M. H., Rogers C. M., Lubin M. F., Fleming G. A., Bain R. P. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest. 1981 May;67(5):1361–1369. doi: 10.1172/JCI110164. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salomon F., Cuneo R. C., Hesp R., Sönksen P. H. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989 Dec 28;321(26):1797–1803. doi: 10.1056/NEJM198912283212605. [DOI] [PubMed] [Google Scholar]
- Sjöberg A., Oscarsson J., Boström K., Innerarity T. L., Edén S., Olofsson S. O. Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver. Endocrinology. 1992 Jun;130(6):3356–3364. doi: 10.1210/endo.130.6.1597147. [DOI] [PubMed] [Google Scholar]
- Spady D. K., Cuthbert J. A. Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7 alpha-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme A reductase or low density lipoprotein receptor. J Biol Chem. 1992 Mar 15;267(8):5584–5591. [PubMed] [Google Scholar]
- Spady D. K., Dietschy J. M. Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4526–4530. doi: 10.1073/pnas.82.13.4526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spady D. K., Dietschy J. M. Interaction of dietary cholesterol and triglycerides in the regulation of hepatic low density lipoprotein transport in the hamster. J Clin Invest. 1988 Feb;81(2):300–309. doi: 10.1172/JCI113321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staels B., van Tol A., Chan L., Verhoeven G., Auwerx J. Variable effects of different corticosteroids on plasma lipids, apolipoproteins, and hepatic apolipoprotein mRNA levels in rats. Arterioscler Thromb. 1991 May-Jun;11(3):760–769. doi: 10.1161/01.atv.11.3.760. [DOI] [PubMed] [Google Scholar]
- Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
- Thorner M. O., Vance M. L. Growth hormone, 1988. J Clin Invest. 1988 Sep;82(3):745–747. doi: 10.1172/JCI113673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wüster C., Slenczka E., Ziegler R. Erhöhte Prävalenz von Osteoporose und Arteriosklerose bei konventionell substituierter Hypophysenvorderlappeninsuffizienz: Bedarf einer zusätzlichen Wachstumshormonsubstitution? Klin Wochenschr. 1991 Oct 18;69(16):769–773. doi: 10.1007/BF01797616. [DOI] [PubMed] [Google Scholar]