Effects of Thyroid Hormones on Cellular RNA Metabolism

Towle, Howard C.

doi:10.1016/b978-0-12-527560-6.50012-3

Cited by 13 publications

(6 citation statements)

References 102 publications

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“…These mRNAs, therefore, are precluded as controls in studies of T3 action in cultured cells. Riboso¬ mal RNA may be influenced also by hormonal status, but only 0-50% depending on cell type (23), and is thus the preferred control in standard northern blotting experiments.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells

Barlow

Crowe²,

Cowen³

et al. 1994

European Journal of Endocrinology

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We examined the time course and dose response of the triiodothyronine (T3) effect on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T3, SHBG mRNA was unchanged but increased to 1.5 +/- 0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3 +/- 0.6) was observed at 2-3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h after exposure to T3 but diminished thereafter to 64% by day 3. At 3-4 days of exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T3 concentration. For both mRNAs, half-maximal response occurred between 10 and 20 pmol/l bioavailable T3. Cortisol-binding proteins secreted by HepG2 cells after 3 days in culture also were T3 dose-responsive. No re-uptake of secreted CBG by the cells was observed, suggesting that the T3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T3 stimulates the expression of the SHBG gene and attenuates the expression of the CBG gene. The effects of T3 on these genes are consistent with the increase in circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The HepG2 cells may be a useful human cell line in which to study the diversity of the molecular mechanisms of T3 action.

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Section: Discussionmentioning

confidence: 99%

Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells

Barlow

Crowe²,

Cowen³

et al. 1994

European Journal of Endocrinology

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“…As reported earlier (Luo et al 1988), the anterior pituitary possesses the highest receptor density, whereas in the inter¬ mediate lobe immunoreactivity was almost com¬ pletely absent and few cells stained in the posterior lobe. It is known that thyroid hormones can inde¬ pendently influence the secretory activities of somatotrope, lactotrope and thyrotrope cells (Towle 1983;Larsen & Silva 1983). Both cell types, somatotrope and lactotrope themselves, represent 60% of the total anterior pituitary cells (Morianty 1973).…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical localization of the nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen

Luo¹,

Faure²,

Tong³

et al. 1989

Acta Endocrinologica

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A monoclonal antibody was used for the localization of the nuclear T3 receptor in different tissues of the adult rat: the liver, kidney, heart, lung, spleen, testis, and pituitary. In the liver, the immunoreactivity was found uniformly distributed in the nuclei of hepatocytes.Sections incubated with a control ascitic fluid or with the same ascitic fluid pre-adsorbed with purified receptor showed no specific staining. In the kidney, the immunoreactivity was higher in the epithelial cell of the proximal convoluted tubes and juxtaglomerular cells. In the heart, only the myocardial cells were stained. In the lung, the immunoreactivity was confined to type II pneumocytes and alveolar macrophages. In the spleen, only a few mature lymphocyte and macrophage cell nuclei were stained. These results show that: 1) the abundance of the nuclear T3 correlates with previous studies using hormone binding techniques; 2) the nuclear T3 receptor is selectively located in certain cell types, which possess a precise local function.Thyroid hormones are thought to elicit their biol¬ ogical activities through interaction with a nuclear receptor (Oppenheimer 1983; Oppenheimer et al. 1987). Much information has been obtained on re¬ ceptor structure and function using radiolabelled hormone of high specific activity. Antibodies pro¬ vide an additional tool with which to study recep¬ tors either bound or unbound to their ligand in a variety of physiological conditions. The produc¬ tion of polyclonal, and more recently, monoclonal antibodies against the 3,5,3'-triiodothyronine (T3) receptor using rat liver as a source of antigen have been documented (Faure et al. 1986;Luo et al. 1988). We have shown by means of protein blotting techniques (Luo et al. 1988) that the tissue distribu¬ tion profile of the receptor is similar to the ones re¬ ported in previous results obtained by hormone saturation analysis (Oppenheimer et al. 1974).These studies, however, do not document the cell type distribution of the T3 receptor as this infor¬ mation is clearly important to understand the basis of the biological action of thyroid hormones. We have therefore utilized immunocytochemical techniques on frozen tissue sections to study the cellular localization of the receptor in liver, kidney, heart, lung and spleen of the adult rat. Materials and Methods MaterialsSprague-Dawley male rats (150-200 g) were obtained from a commercial supplier (Canadian Breeding Farms, St. Constant-Laprairie, Canada). The animals were housed in attenuated sound and temperature, light con¬ trolled room, and allowed free access to rat faboratory chow and water. The anti-mouse IgG, peroxidase antiperoxidase (PAP) compiexes and anti-mouse IgG conjugated with fluorescein isothiocyanate (FITC) were kindly provided by Dr G. Pelletier and Dr J. P. Valet (C.H.U.L., Québec), 3,3'-diaminobenzidine tetrahydrochloride (DAB) and anti-foam A emulsion were pur¬ chased from Sigma (St. Louis, MO).

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“…The dose of T 3 and the treatment duration were chosen so as to provide us with hyperthyroid, but not thyreotoxic, animals (26,27). A commercial mash and water were available ad libitum.…”

Section: Animalsmentioning

confidence: 99%

Uncoupling Protein-3 Is a Molecular Determinant for the Regulation of Resting Metabolic Rate by Thyroid Hormone

et al. 2001

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Thyroid hormones increase energy expenditure, partly by reducing metabolic efficiency. The control of specific genes at the transcriptional level is thought to be the major molecular mechanism. However, both the number and the identity of the thyroid hormone-controlled genes remain unknown, as do their relative contributions. Uncoupling protein-3, a recently identified member of the mitochondrial transporter superfamily and one that is predominantly expressed in skeletal muscle, has the potential to be a molecular determinant for thyroid thermogenesis. However, changes in mitochondrial proton conductance and resting metabolic rate after physiologically mediated changes in uncoupling protein-3 levels have not been described. Here, in a study on hypothyroid rats given a single injection of T(3), we describe a strict correlation in terms of time course between the induced increase in uncoupling protein-3 expression (at mRNA and protein levels) and decrease in mitochondrial respiratory efficiency, on the one hand, and the increase in resting metabolic rate, on the other. First, we describe our finding that uncoupling protein-3 is present and regulated by T(3) only in metabolically relevant tissues (such as skeletal muscle and heart). Second, we follow the time course (at 0, 6, 12, 24, 48, 65, 96, and 144 h) of both uncoupling protein-3 mRNA levels and mitochondrial uncoupling protein-3 density in gastrocnemius muscle and heart. In both tissues, the maximal (12-fold) increase in uncoupling protein-3 density was reached at 65 h. The resting metabolic rate [lO(2)(kg(0.75))(-1)h(-1)] showed the same time course, and at 65 h the increase vs. time zero was 45% (1.316 +/- 0.026 vs. 0.940 +/- 0.007; P < 0.001). At the same time point, gastrocnemius muscle mitochondria showed a significantly higher nonphosphorylating respiration rate (nanoatoms of oxygen per min/mg protein; increase vs. time zero, 40%; 118 +/- 4 vs. 85 +/- 9; P < 0.05), whereas the membrane potential decreased by 8% (168 +/- 2 vs. 182 +/- 4; P < 0.05). These data are diagnostic of mitochondrial uncoupling. The results reported here provide the first direct in vivo evidence that uncoupling protein-3 has the potential to act as a molecular determinant in the regulation of resting metabolic rate by T(3).

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Effects of Thyroid Hormones on Cellular RNA Metabolism

Cited by 13 publications

References 102 publications

Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells

Stimulation of sex hormone-binding globulin mRNA and attenuation of corticosteroid-binding globulin mRNA by triiodothyronine in human hepatoma cells

Immunocytochemical localization of the nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen

Uncoupling Protein-3 Is a Molecular Determinant for the Regulation of Resting Metabolic Rate by Thyroid Hormone

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