Effect of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle

Carter, W J; Benjamin, Wieke S. van der Weijden; Faas, Fred H.

doi:10.1016/0026-0495(80)90032-3

Cited by 38 publications

(19 citation statements)

References 20 publications

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“…The role of T3 in amino acid incorporation and biosynthesis of DNA and protein constituents has been well studied (reviewed by Schwartz and Oppenheimer [52]). T3 has also been shown to increase protein turnover in both cardiac and skeletal muscle (1,10,11). In rats, skeletal muscle protein content following T3 administration is reduced due to increased proteolysis (1).…”

Section: Resultsmentioning

confidence: 99%

Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-Stimulated Cell Proliferation

Miller

Park

Guo

et al. 2001

Molecular and Cellular Biology

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To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the ␤-catenin-T-cell factor complex. This was confirmed biochemically, as ␤-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a ␤-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.Thyroid hormone (3,3Ј,5-triiodo-L-thyronine [T3]) receptors (TRs) are ligand-dependent transcription factors which are members of the steroid hormone/retinoic acid (RA) receptor superfamily. Two TR genes, TR␣ and TR␤, located on chromosomes 17 and 3, respectively, give rise, by alternative splicing, to three T3-binding TR isoforms, ␣1, ␤1, and ␤2 (reviewed by Cheng [12]). TRs mediate the biological activities of T3 by binding to specific DNA sequences known as the T3 response elements present in the promoter regions of T3 target genes (reviewed by Cheng [12]). The transcriptional regulatory activity of TRs depends not only on T3 and the types of T3 response elements but also on a host of coregulatory proteins, including corepressors, coactivators, and the tumor suppressor p53 (3, 38).The growth-stimulatory effect of T3 has long been recognized. In humans, lack of T3 during development leads to growth retardation and cretinism. Growth retardation is also evident in patients with resistance to T3, a genetic disease due to mutations in the TR␤ gene (54). TR␤1 mutants act in a dominant negative fashion to cause growth retardation and delayed bone maturation (54). Moreover, mutant mice harboring a potent dominant negative mutant TR␤1 also exhibit a similar phenotype (25,60).GC is a rat pituitary cell line that expresses functional TRs and has long been used as a model cell line to understand the mechanisms of T3 action. Previously we have shown that GC cells are induced to proliferate by T3 in cultured medium containing 10% T3-depleted (Td) serum (2, 27). This induction is T3 specific, because the inactive T3 analogs, L-thyronine and reverse T3, failed to stimulate proliferation of GC cells in the same culture medium (27). Recently...

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Section: Resultsmentioning

confidence: 99%

Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-Stimulated Cell Proliferation

Miller

Park

Guo

et al. 2001

Molecular and Cellular Biology

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“…However, the response becomes rational in light of closely mirrored responses observed in thyroid hormone metabolism (in particular, hepatic DIII and plasma T 3 ), which suggest that this negative response is secondary to a GH-induced hyper-T 3 state, and not a direct, primary GH lesion. Net loss of muscle protein occurs in human patients with high serum T 3 (Hasselgren et al 1984, Morrison et al 1988 and in experimental models of hyperthyroidism (Carter et al 1980), and supplemental T 3 reduces body weight gain in chickens (May 1980, Bowen et al 1987, Tixier-Boichard et al 1990.…”

Section: Discussionmentioning

confidence: 99%

Altered chicken thyroid hormone metabolism with chronic GH enhancement in vivo: consequences for skeletal muscle growth

Vasilatos‐Younken¹,

Zhou²,

Wang³

et al. 2000

Journal of Endocrinology

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In contrast to most vertebrates, GH reportedly has no effect upon somatic growth of the chicken. However, previous studies employed only one to two dosages of the hormone, and limited evidence exists of a hyperthyroid response that may confound its anabolic potential. This study evaluated the effects of 0, 10, 50, 100 and 200 µg/kg body weight per day chicken GH (cGH) (0-200 GH) infused i.v. for 7 days in a pulsatile pattern to immature, growing broiler chickens (9-10 birds/dosage). Comprehensive profiles of thyroid hormone metabolism and measures of somatic growth were obtained.Overall (average) body weight gain was reduced 25% by GH, with a curvilinear, dose-dependent decrease in skeletal (breast) muscle mass that was maximal (12%) at 100 GH. This profile mirrored GH dose-dependent decreases in hepatic type III deiodinase (DIII) activity and increases in plasma tri-iodothyronine (T 3 ), with both also maximal (74 and 108% respectively) at 100 GH. No effect on type I deiodinase was observed. At the maximally effective dosage, hepatic DIII gene expression was reduced 44% versus controls. Despite dose-dependent, fold-increases in hepatic IGF-I protein content, circulating IGF-I was not altered with GH infusion, suggesting impairment of hepatic IGF-I release. Significant, GH dose-dependent increases in plasma non-esterified fatty acid and glucose, and overall decreases in triacylglycerides were also observed. At 200 GH, feed intake was significantly reduced (19%; P<0·05) versus controls; however, additional control birds pair-fed to this level did not exhibit any responses observed for GH-treated birds.The results of this study support a pathway by which GH impacts on thyroid hormone metabolism beginning at a pretranslational level, with reduced hepatic DIII gene expression, translating to reduced protein (enzyme) expression, and reflected in a reduced level of peripheral T 3 -degrading activity. This contributes to decreased conversion of T 3 to its inactive form, thereby elevating circulating T 3 levels. The hyper-T 3 state leads to reduced net skeletal muscle deposition, and may impair release of GH-enhanced, hepatic IGF-I.In conclusion, GH has significant biological effects in the chicken, but profound metabolic actions predominate that may confound positive, IGF-I-mediated skeletal muscle growth.

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“…Contributions of hepatic protein synthesis to hepatic 0 2 consumption are available in the literature for a variety of species (Table 3) and are affected by physiological manipulation. Similarly, the gastrointestinal tract contributes substantially to wholebody 0 2 utilization (Huntington & McBride, 1988), and even though it only amounts to Thyroidectomy decreases the FSR of skeletal muscle in rats (Brown & Millward, 1983) whereas T3 treatment of mice or rats increases rates of protein synthesis (Carter et al 1982;Bates & Holder, 1988;Jepson et al 1988) (see Table 4). The study of Jepson et al (1988) indicated a significant linear relationship between the rate of muscle protein synthesis and T3 treatment.…”

Section: Protein S Y N T H E S I Smentioning

confidence: 99%

The sodium pump and other mechanisms of thermogenesis in selected tissues

Kelly

McBride

1990

Proc. Nutr. Soc.

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Whole-body heat production is a consequence of several biochemical events. Specific sites of heat production have been isolated, some being greater contributors to whole-body oxygen consumption than others. Tissues of the splanchnic bed (the gastrointestinal tract and liver) make up only 4 4 % of whole-body mass, but account for 40% of total ATP utilization. Skeletal muscle accounts for a much larger proportion of whole-body mass (50%), but accounts for only 20% of whole-body ATP use. Two major biochemical events contributing to energy use are Na+,K+-ATPase (EC 3.6.1.3) activity and protein turnover. Discussion of these two processes will dominate the present paper but reference will be made to other energy-consuming processes within selected tissues.First, a major contributor to cellular energetics is the activity of the enzyme Na+,K+-ATPase, which extrudes three Na+ from the cell and moves two K' into the cell against their respective concentration gradients at the cost of one high-energy phosphate bond (Balaban et al. 1980). The actions of this enzyme are responsible for the active transport of substrates, maintenance of ionic homeostasis, membrane potential and cell multiplication (Rosier et al.

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Effect of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle

Cited by 38 publications

References 20 publications

Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-Stimulated Cell Proliferation

Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-Stimulated Cell Proliferation

Altered chicken thyroid hormone metabolism with chronic GH enhancement in vivo: consequences for skeletal muscle growth

The sodium pump and other mechanisms of thermogenesis in selected tissues

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