Endocrinology, Vol 127, 1144-1152, Copyright © 1990 by Endocrine Society

ARTICLES

Alterations in thyroid status modulate apolipoprotein, hepatic triglyceride lipase, and low density lipoprotein receptor in rats

B Staels, A Van Tol, L Chan, H Will, G Verhoeven and J Auwerx
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Katholieke Universiteit, Leuven, Belgium.

The influence of altered thyroid state is investigated on plasma apolipoprotein-A-I (apo-A-I), apo-B, and apo-E levels and on apo-A-I, apo-A-II, apo-B, apo-E, hepatic triglyceride lipase (HTGL), and low density lipoprotein (LDL) receptor mRNA levels in rat liver and intestine. Plasma total cholesterol and triglycerides are unchanged in hyperthyroid rats. Liver apo-A-I mRNA levels increase 3-fold, whereas intestinal apo-A-I mRNA levels remain constant. Plasma apo-A-I levels almost double after L-T4. Liver apo-B and apo-E and intestinal apo-B mRNA levels are not influenced by L-T4, but plasma apo-B and apo-E decrease significantly. In the liver, apo-A-II mRNA levels decrease, whereas LDL receptor mRNA levels increase more than 50%. HTGL mRNA is not influenced by L-T4. N-Propyl-thiouracil-induced hypothyroidism does not influence plasma triglycerides, but plasma cholesterol levels nearly double. Liver and intestinal apo-A-I mRNA levels and plasma apo- A-I concentrations remain constant after propylthiouracil treatment. Accompanying the increase in plasma apo-B, liver and intestinal apo-B mRNA concentrations rise by approximately 100% and 40%, respectively. Plasma apo-E increases nearly 2-fold, but liver, apo-A-II mRNA rises, whereas HTGL and LDL receptor mRNA levels decrease 20% and nearly 50%, respectively. In conclusion, thyroid hormones regulate rat apo-A-I and apo-A-II gene expression in opposite directions. Furthermore, the LDL receptor is regulated at the mRNA level, whereas HTGL gene expression is relatively resistant to alterations in thyroid status.

This article has been cited by other articles:

				M. Ito, T. Arishima, T. Kudo, E. Nishihara, H. Ohye, S. Kubota, S. Fukata, N. Amino, K. Kuma, I. Sasaki, et al. Effect of Levo-Thyroxine Replacement on Non-High-Density Lipoprotein Cholesterol in Hypothyroid Patients J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 608 - 611. [Abstract] [Full Text] [PDF]

				V. A. B. Drover and L. B. Agellon Regulation of the Human Cholesterol 7{alpha}-Hydroxylase Gene (CYP7A1) by Thyroid Hormone in Transgenic Mice Endocrinology, February 1, 2004; 145(2): 574 - 581. [Abstract] [Full Text] [PDF]

				A. R. Cappola and P. W. Ladenson Hypothyroidism and Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2438 - 2444. [Full Text] [PDF]

				H. Gullberg, M. Rudling, C. Salto, D. Forrest, B. Angelin, and B. Vennstrom Requirement for Thyroid Hormone Receptor {beta} in T3 Regulation of Cholesterol Metabolism in Mice Mol. Endocrinol., August 1, 2002; 16(8): 1767 - 1777. [Abstract] [Full Text] [PDF]

				C. Galman, B. Angelin, and M. Rudling Prolonged Stimulation of the Adrenals by Corticotropin Suppresses Hepatic Low-Density Lipoprotein and High-Density Lipoprotein Receptors and Increases Plasma Cholesterol Endocrinology, May 1, 2002; 143(5): 1809 - 1816. [Abstract] [Full Text] [PDF]

				G. P. Hayhurst, Y.-H. Lee, G. Lambert, J. M. Ward, and F. J. Gonzalez Hepatocyte Nuclear Factor 4{alpha} (Nuclear Receptor 2A1) Is Essential for Maintenance of Hepatic Gene Expression and Lipid Homeostasis Mol. Cell. Biol., February 15, 2001; 21(4): 1393 - 1403. [Abstract] [Full Text]

				H. Gullberg, M. Rudling, D. Forrest, B. Angelin, and B. Vennström Thyroid Hormone Receptor {beta}-Deficient Mice Show Complete Loss of the Normal Cholesterol 7{alpha}-Hydroxylase (CYP7A) Response to Thyroid Hormone but Display Enhanced Resistance to Dietary Cholesterol Mol. Endocrinol., November 1, 2000; 14(11): 1739 - 1749. [Abstract] [Full Text]

				J. D. Medh, S. L. Bowen, G. L. Fry, S. Ruben, J. Hill, H. Wong, and D. A. Chappell Hepatic triglyceride lipase promotes low density lipoprotein receptor-mediated catabolism of very low density lipoproteins in vitro J. Lipid Res., July 1, 1999; 40(7): 1263 - 1275. [Abstract] [Full Text]

				M. Weintraub, I. Grosskopf, Y. Trostanesky, G. Charach, A. Rubinstein, and N. Stern Thyroxine Replacement Therapy Enhances Clearance of Chylomicron Remnants in Patients with Hypothyroidism J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2532 - 2536. [Abstract] [Full Text]

				K. C. B. Tan, S. W. M. Shiu, and A. W. C. Kung. Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2921 - 2924. [Abstract] [Full Text]

				K. C. B. Tan, S. W. M. Shiu, and A. W. C. Kung Plasma Cholesteryl Ester Transfer Protein Activity in Hyper- and Hypothyroidism J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 140 - 143. [Abstract] [Full Text]

				J. Blangero, S. Williams-Blangero, M. C. Mahaney, A. G. Comuzzie, J. E. Hixson, P. B. Samollow, R. M. Sharp, M. P. Stern, and J. W. MacCluer Effects of a Major Gene for Apolipoprotein A-I Concentration Are Thyroid Hormone Dependent in Mexican Americans Arterioscler. Thromb. Vasc. Biol., September 1, 1996; 16(9): 1177 - 1183. [Abstract] [Full Text]