TTF-1 action on the transcriptional regulation of Cyclooxygenase-2 gene in the rat brain

Chang Ho Yun, Jae Geun Kim, Byong Seo Park, Hye Myeong Lee, Dong Hee Kim, Eun Ok Kim, Joong Jean Park, Jeong Woo Park, Giuseppe Damante, Young Il Kim, Byung Ju Lee

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Abstract

We have recently found that thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is postnatally expressed in discrete areas of the hypothalamus and closely involved in neuroendocrine functions. We now report that transcription of cyclooxygenase-2 (COX-2), the rate limiting enzyme in prostaglandin biosynthesis, was inhibited by TTF-1. Double immunohistochemistry demonstrated that TTF-1 was expressed in the astrocytes and endothelial cells of blood vessel in the hypothalamus. Promoter assays and electrophoretic mobility shift assays showed that TTF-1 inhibited COX-2 transcription by binding to specific binding domains in the COX-2 promoter. Furthermore, blocking TTF-1 synthesis by intracerebroventricular injection of an antisense oligomer induced an increase of COX-2 synthesis in non-neuronal cells of the rat hypothalamus, and resulted in animals' hyperthermia. These results suggest that TTF-1 is physiologically involved in the control of thermogenesis by regulating COX-2 transcription in the brain.

Original languageEnglish
Article numbere28959
JournalPLoS One
Volume6
Issue number12
DOIs
Publication statusPublished - 2011 Dec 13

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yun, C. H., Kim, J. G., Park, B. S., Lee, H. M., Kim, D. H., Kim, E. O., Park, J. J., Park, J. W., Damante, G., Kim, Y. I., & Lee, B. J. (2011). TTF-1 action on the transcriptional regulation of Cyclooxygenase-2 gene in the rat brain. PLoS One, 6(12), [e28959]. https://doi.org/10.1371/journal.pone.0028959