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Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis

Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi, Japan

Submitted 11 May 2008 ; accepted in final form 12 June 2008

C.RF- Tshr^hyt/hyt mice have a mutated thyroid-stimulating hormone receptor (TSHR), and, without thyroid hormone supplementation, these mice develop severe hypothyroidism. When hypothyroid Tshr^hyt/hyt mice were exposed to cold (4°C), rectal temperature rapidly dropped to 23.9 ± 0.40°C at 90 min, whereas the wild-type mice temperatures were 37.0 ± 0.15°C. When we carried out functional rat TSHR gene transfer in the brown adipose tissues by plasmid injection combined with electroporation, there was no effect on the serum levels of thyroxine, although rectal temperature of the mice transfected with pcDNA3.1/Zeo-rat TSHR 90 min after cold exposure remained at 34.6 ± 0.34°C, which was significantly higher than that of Tshr^hyt/hyt mice. Transfection of TSHR cDNA increased mRNA and protein levels of uncoupling protein-1 (UCP-1) in brown adipose tissues, and the weight ratio of brown adipose tissue to overall body weight also increased. Exogenous thyroid hormone supplementation to Tshr^hyt/hyt mice restored rectal temperature 90 min after exposure to cold (36.8 ± 0.10°C). These results indicate that not only thyroid hormone but also thyroid-stimulating hormone (TSH)/TSHR are involved in the expression mechanism of UCP-1 in mouse brown adipose tissue. TSH stimulates thermogenesis and functions to protect a further decrease in body temperature in the hypothyroid state.

in vivo electroporation; brown adipose tissues; thyroid hormone; uncoupling protein-1

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