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An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray
1Molecular Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression in vivo and should prove to be a powerful tool for future studies of hormone and drug action.
Insights
Thyroid hormone impacts liver gene expression, regulating diverse cellular functions. This study identified 55 new genes, many negatively controlled by thyroid hormone, using advanced microarray technology.
Area of Science:
- Hormone research
- Molecular biology
- Genomics
Background:
- The liver is a key target organ for thyroid hormone.
- Limited knowledge exists regarding specific hepatic target genes and their regulation patterns by thyroid hormone.
Purpose of the Study:
- To identify novel hepatic genes regulated by thyroid hormone.
- To elucidate the regulatory patterns of thyroid hormone on gene expression in the liver.
Main Methods:
- Quantitative fluorescent cDNA microarray analysis was employed.
- Hepatic RNA from T3-treated and hypothyroid mice was used.
- Gene expression changes were compared using computer analysis on a 2225-gene microarray.
Main Results:
- Fifty-five genes were found to be regulated by thyroid hormone.
- 45 of these genes were previously unknown to be thyroid hormone-responsive.
- Unexpectedly, 41 genes were negatively regulated, while 14 were positively regulated.
- Thyroid hormone influenced diverse pathways including gluconeogenesis, lipogenesis, and apoptosis.
Conclusions:
- This study significantly expands the known repertoire of thyroid hormone-responsive genes in the liver.
- Microarray technology offers a powerful approach for studying in vivo hormonal regulation of gene expression.
- Thyroid hormone exerts broad control over hepatic cellular functions, including metabolism and cell fate.
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