Horomones and Growth FactorsEffects of l-Triiodothyronine and the Thyromimetic L-94901 on Serum Lipoprotein Levels and Hepatic Low-Density Lipoprotein Receptor, 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase, and Apo A-I Gene Expression
Section snippets
Experimental Animals and Design
Surgically thyroparathyroidectomized and sham-operated control male Sprague–Dawley rats weighing between 200 and 250 g, from Charles Rivers, were housed in a reversed-cycle light-controlled room (light from 3:00 p.m. to 3:00 a.m.). These animals carry about 30% of their cholesterol in the form of LDL and 65% in HDL (see Table 1). Upon thyroidectomy, the portion carried in LDL increases to 50%. In many respects, these changes closely parallel the responses to thyroid dysfunction and thyroid
Alterations in Plasma Lipid and Lipoprotein Concentrations in Response to Thyroidectomy
Hypothyroidism induced by surgical thyroidectomy of rats caused marked alterations in circulating lipid and lipoprotein concentrations relative to sham-operated control animals. This is similar to that previously noted in animals rendered hypothyroid either surgically or by treatment with propylthiouracil [16]. As shown in Fig. 1, total plasma cholesterol concentrations were essentially unaffected by thyroidectomy. However, plasma TG concentrations were reduced by 60%. Fractionation of serum
Discussion
The results of this study demonstrate that both the thyroid hormone and the thyromimetic L-94901 induce the hepatic LDL receptor, leading to significant decreases in LDL cholesterol levels. In addition, they also caused substantial increases in HDL levels, likely due to induction of apo A-I. Thus, the ratio of LDL to HDL in thyroidectomized rats was reduced from 1.01 to 0.25 in response to T3 and to 0.12 upon treatment with L-94901. Unlike the bile acid binding resins and the statins, T3 and
Acknowledgements
We thank Donald E. Wilder for conducting the FPLC separation of lipoprotein subclasses, Kelly A. Martin for measurement of plasma T4 concentrations, Robert L. Dow for preparing the thyromimetic L-94901 used in these studies, and Pfizer, Inc. for a grant to G. C. N., supporting these studies.
References (32)
- et al.
Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid
Biochem Pharmacol
(1992) - et al.
The effects of altered thyroid status on lipid metabolism in the genetic hyperlipemic Zucker rat
Atherosclerosis
(1981) - et al.
Lipid and lipoprotein patterns in thyroid dysfunction and the effect of therapy
Clin Biochem
(1982) - et al.
Effect of hypothyroidism, diabetes and polyunsaturated fatty acids on heparin-releasable rat liver lipase
Biochem Biophys Res Commun
(1977) - et al.
Effect of thyroid hormones on acid cholesterol ester hydrolase activity in rat liver, heart and epididymal fat pads
Biochim Biophys Acta
(1981) - et al.
Pharmacologic consequences of cholesterol absorption inhibitionAlteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin β-tigogenin cellobioside (CP-88818; tiqueside)
J Lipid Res
(1993) - et al.
Thyroid hormone rapidly induces hepatic LDL receptor mRNA levels in hypophysectomized rats
Arch Biochem Biophys
(1994) - et al.
Transcriptional regulation of rat hepatic LDL receptor and cholesterol 7α-hydroxylase
Arch Biochem Biophys
(1995) - et al.
Influence of thyroid hormones on l-α-glycerophosphate dehydrogenases and other dehydrogenases in various organs of the rat
J Biol Chem
(1965) - et al.
Translational regulation of hepatic HMG-CoA reductase by dietary cholesterol
Biochem Biophys Res Commun.
(1997)
Effect of thyroid hormone on hepatic cholesterol 7α hydroxylase, LDL receptor, HMG-CoA reductase, farnesyl pyrophosphate synthetase and apolipoprotein A-I mRNA levels in hypophysectomized rats
Biochem Biophys Res Commun
Effect of squalene synthase inhibition on the expression of hepatic cholesterol biosynthetic enzymes, LDL receptors and cholesterol 7α-hydroxylase
Arch Biochem Biophys
Differential regulation of hepatic apolipoprotein A-I and A-II gene expression by thyroid hormone in rat liver
Atherosclerosis
Thyroid hormone influences the maturation of apolipoprotein A-I messenger RNA in rat liver
J Biol Chem
Thyroid hormone influences conditional transcript elongation of the apolipoprotein A-I gene in rat liver
J Lipid Res
Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation
Arch Biochem Biophys
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2014, Molecular and Cellular EndocrinologyCitation Excerpt :T3 similarly induces some genes that play important regulatory roles in cholesterol metabolism in both species, such as liver LDL receptor (Bakker et al., 1998). While T3 strongly induces Cyp7a1 expression in rodents (Gullberg et al., 2002; Johansson et al., 2005; Shin et al., 2006; Hashimoto et al., 2006; Kamiya et al., 2003; Ness et al., 1994, 1998; Hylemon et al., 1992), several lines of evidence suggest that the human Cyp7a1 gene could respond differently. First, assessment of cholic acid (CA) levels in humans have indicated that CA secretion rates into the intestine, CA synthesis and pool size are all decreased in hyperthyroid patients and restored by normalization of TH levels (Sauter et al., 1997).