- Serum Leptin Levels in Patients with Thyroid Dysfunction.
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Min hO Song, Young Kun Kim, Heung Kyu Ro, Hee Jung Han, Won Chan Joo, Jin Ho Won, Yoon Kim, Hyun Jin Kim, Soo Heung Chae
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J Korean Endocr Soc. 1999;14(2):372-378. Published online January 1, 2001
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 Abstract
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- BACKGROUND
Leptin, the product of ob gene, is an important circulating hormone for the regulation of homeostasis of body weight and enegy expenditure. There was a previous reports that thyroid hormone is one of regulating factors of leptin gene expression in vitro. The aim of this study was designed to evaluate the role of thyroid hormone levels in the regulation of circulating leptin concentrations in human. METHODS: A total 16S subjects were studied; 76 patients with Graves disease, 49 patients with Hashimoto disease and 43 control sujjects. The correlation between thryoid hormone and leptin levels were analyzed and serum leptin levels were compared among the groups which was classified by thyroid functional status. Serum leptin concentratios were measured by radioimmunoassay. RESULTS: There were no significant differences in serum leptin levels between the groups of control, Graves disease and Hashimoto disease. The hypothyroid groups of Graves disease which was induced by excessive antithyroid drug treatment showed significant low levels(5.6 +/-2.8 ng/mL) compared to control(9.6 +/- 5.2 ng/ml) and thyrotoxic groups(10.0 +/- 5,0 ng/mL) CONCLUSION: The hypothyroid patients showed low levels of serum leptin concentrations it may indicate that thyroid horrnone play a role in the appropriate secretion of leptin in human.
- Thyrotropin Suppresses INF-r Mediated Gene Expression by Inhibiting Signal Transducer and Activation of Transcription 1(STAT1) Activity in FRTL-5 Cells.
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Min Ho Song, Young Kun Kim, Heung Kyu Ro, Eun Shin Park, Soon Hee Yoo, Ho Kim, Kang Wook Lee, Hee Jung Han, Won Chan Joo, Jin Ho Won, Kyu Lim, Oh Yoo Kwon
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J Korean Endocr Soc. 1998;13(4):536-553. Published online January 1, 2001
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Abstract
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- BACKGROUND
The proinflammatory cytokine, IFN-y has been shown to exert pleiotropic effects in a variety of pathophysiologic conditions in autoimmune thyroid disease. The thyrocyte response to IFN-y is mediated two distinct classes of proteins, Janus kinases(Jakl and Jak2) and Signal Transducers and Activation of Transcription(STATl). The activation of STAT 1 is involved in the regulation of many interferon stimulated genes, such as MHC class II, intercellular adhesion molecules-1(ICAM-1) and MHC class II transactivator(CIITA) after the binding to the GASgFN- pactivated site) of the gene promoters. Recently we found TSH/forskolin inhibits IFN-y stimulated maximal expression of ICAM-1 in FRTL-5 cell. IFN-y action is localized between -175 bp and -97 bp from the start of translation of ICAM-1 gene which contains regulatory elements known to be involved in IFN-y action in other eukaryotic cells, palindromic IFN-y activated site(GAS)(5-TTTCCGGGAAA-3) which could bind STAT1, STAT3, STAT5, STAT6. Furthermore, the addition of TSH and forskolin causes a decrease in ICAM-1 promoter activity and its action was localized in GAS. These findings suggested TSH/cAMP signaling pathways downregulate IFN-y activated Janus kinase-STAT signaling path. We wanted to explore the possible involvement of elevated cAMP in the negative regulation of IFN-y induced STAT1 activation in thyroid cells. METHOD: We made several 5-deletion constructs of rat ICAM-1 promoter and analyzed the promoter activities by measuring the luciferase activity after tranfection into FRTL-5 cells. The protein/DNA complex was measured by electrophoretic mobility shift analysis using labeled oligonucleotide. We checked the level of total and phosphorylated STATl protein by immunoblot analysis using specific antibodies. RESULTS: Stimulation of IFN-y in FRTL-5 cells resulted in rapid activation of STATl/DNA binding activity, which was apparent after several minute of stimulation, maintains its activity until 48 h. Incubation of cells with TSH result in suppression of IFN-p mediated STAT1/DNA binding activity throughout the time course of activation by IFN-y. Addition of TSH into 5H maintained FRTL-5 cells did not change the total amount of latent STAT1 amount and also not affect IFN-y mediated production of total STAT1 until 4 h. IFN-y(100 U/mL) rapidly induced phosphorylation of STAT1 within 30 min. and maintained its level without significant change until 48 hours. Cells treated with TSH dramatically lowered the level of IFN-y induced production and phosphorylation of STAT1 after 12 h, 24 h, 36 h, and 48 h but TSH had no effect on the level of phosphorylated STATl within 4 h after IFN-y stimulation. The proteasome inhibitor, MG132 and phosphatase inhibitor, sodium orthovanadate did not block the TSH or forskolin mediated downregulation of phosphorylated STAT1. CONCLUSION: These results indicate a regulatory mechanism which TSH signaling can modulate the prolonged activation of Jak/Stat by IFN-y. We identified one of mechanisms related to TSH mediated negative suppression of the ICAM-1 gene; TSH/cAMP signaling pathways downregulate the cytokine activated Janus kinase-STAT signaling path.
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