TTF-1 Action on the Transcriptional Regulation of Cyclooxygenase-2 Gene in the Rat Brain

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.

Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways

“…In the gut, for example, COX-2 may be driven through proliferative pathways such as MAPK as a byproduct of continual epithelial proliferation. Alternatively, in the brain, COX-2 may be constitutively induced through neuronal activity and associated transcriptional pathways including cAMP response element-binding protein (CREB), whose pattern of constitutive activity bears striking similarity to that of COX-2 (21), and thyroid-transcription factor-1 (TTF-1), which has been linked to COX-2 in certain brain regions (22).…”

Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation

“…PGE 2 , a prostaglandin synthesized by cyclooxygenases (COX), plays a key role in regulating body temperature (Cao et al 1997, Feleder et al 2004. Indeed, several studies suggest astrocyte PGE 2 production may influence body temperature regulation (Yun et al 2011, Kageyama et al 2013) by altering the function of adjacent neurons (Clasadonte et al 2011). Previous studies in humans have shown that blockade of PGE 2 production by COX inhibitors can lead to hypothermia (Donaldson & Keatinge 1997).…”

Gene expression, function, and diversity of Nkx2-4 in the rainbow trout, Oncorhynchus mykiss

“…However, differently from mammalian NKX2-1, Nk2.1b transcripts were reported to be expressed not in the thyroid (Wendl et al, 2002), but in the ventral telencephalon (Ganz et al, 2012). Mammalian NKX2-1 is also observed in the brain, lung, and parafollicular C-cells (Damante et al, 2001;Yun et al, 2011). Considering these lines of evidence, trout Nkx2-1 Fig.…”