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Am J Physiol Endocrinol Metab 295: E514-E518, 2008. First published June 17, 2008; doi:10.1152/ajpendo.90433.2008
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Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis

Toyoshi Endo and Tetsuro Kobayashi

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


   ABSTRACT
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 ABSTRACT
MATERIALS AND METHODS
 RESULTS AND DISCUSSION
 REFERENCES
 
C.RF- Tshrhyt/hyt mice have a mutated thyroid-stimulating hormone receptor (TSHR), and, without thyroid hormone supplementation, these mice develop severe hypothyroidism. When hypothyroid Tshrhyt/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 Tshrhyt/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 Tshrhyt/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

THYROID-STIMULATING HORMONE receptor (TSHR) is a key molecule in the regulation of thyroid functions, including hormone synthesis, secretion, and cell growth (10).

TSHR expression has long been considered to specifically occur in the thyroid gland. However, Vízek et al. reported that thyroid-stimulating hormone (TSH) stimulated glycerol release from human adipose tissue of a newborn but not of an adult (22). Marcus et al. also demonstrated that TSH is the dominating lipolytic hormone in vitro during the human neonatal period (3), suggesting the existence of functional TSHR in human adipocytes in the neonatal period.

Subsequently, we cloned functional TSHR cDNA from rat adipose tissues (4, 7), proposing that this extrathyroidal TSHR may play important roles in the pathogenesis of extrathyroidal manifestations of Graves' disease. At present, it has been reported that TSHR is detectable in a variety of cell types, including the thymus, bone, heart, lymphocytes, and retroorbital fibroblasts (3). TSHR expression levels in these tissues are relatively low, and in some cases only detectable by highly sensitive methods such as RT-PCR. In contrast, rat adipose tissues expressed high level of TSHR, a level that is almost comparable to that of the thyroid (4). Why such a large amount of TSHR is expressed in the adipose tissues remains to be elucidated.

C.RF-Tshrhyt/hyt mice are hypothyroid with severely hypoplastic thyroid glands because of a mutation in the fourth transmembrane domain of TSHR (20). A proline-to-leucine mutation at codon 556 results in plasma membrane targeting (6), but defective TSH binding and receptor function (6, 20) provides a suitable model for studying the role of extrathyroidal TSHR. Through in vivo electroporation of functional rat TSHR gene into the brown adipose tissues (BAT) of C.RF-Tshrhyt/hyt mice, we studied the role of TSHR in the regulation of BAT thermogenesis.


   MATERIALS AND METHODS
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 ABSTRACT
 MATERIALS AND METHODS
RESULTS AND DISCUSSION
 REFERENCES
 
Animals. All studies were approved by the Animal Research Committee of the University of Yamanashi. C.RF-Tshrhty/– mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and were bred to generate experimental animals. The mice were kept in a specific pathogen free mouse room void of thyroid hormone supplementation. Supplementation of Tshrhyt/hyt mice with thyroid hormones was carried out by intraperitoneal injection of thyroxine (T4; 0.1 µg in 50 µl of saline) for 3 wk according to the methods of Green et al. (5). All mice were 70–84 days old at the start of the experiments. To determine TSHR genotype, we carried out PCR using tail DNA with the following primers: 5'-GGCAATATCTTCGTCCTGCTC-3' and 5'-GATGATCTTCAGATA GCAGG-3' (20). The nucleotide at codon 556, CCG or CTG, was determined by directly sequencing the PCR products. Rectal temperature of the mice was measured using a Digital Thermometer (model TD-300; Shibaura Electronics, Tokyo, Japan). Triiodothyronine (T3) in BAT was extracted with methanol according to the method of Morreale de Escobar et al. (12). Serum free T4 and tissue T3 were assayed by the ECLusis system (Roche Diagnostic, Tokyo, Japan). BAT cAMP was extracted by the methods of Rubio et al. (19) and assayed by a commercially available RIA kit (Yamasa Shoyu, Chiba, Japan). Values are expressed as means ± SE, and statistical analysis was carried out using the Student's t-test.

Gene transfer in BATs by plasmid injection combined with electroporation. pCMV-enhanced green fluorescent protein (EGFP) was constructed by inserting a DNA fragment containing cytomegalovirus (CMV) promoter (Bgl II/Bam HI) from pcDNA3.1/Zeo (Invitrogen, Carlsbad, CA) into pEGFP-1 (CLONTECH Laboratories, Palo Alto, CA). pcDNA3.1/Zeo-rat TSHR was made by inserting rat TSHR cDNA [EcoRI fragment, donated from Dr. Kohn L.D. (Ohio University)] into pcDNA3.1/Zeo. Expression plasmids (pEGFP-1, pCMV-EGFP, pcDNA3.1/Zeo, and pcDNA3.1/Zeo-rat TSHR) were dissolved in 10 µl of sterile PBS (pH 7.4) at a concentration of 2 mg/ml and injected in the left and right side of the BAT using a 27-gauge needle. Electric pulses were delivered using an electric pulse generator (Square Electroporator CUY21; NEPA GENE, Chiba, Japan) with a pair of stainless electrode needles. Two pulses of 70 V for 50 ms followed by two more pulses of the opposite polarity were administered at a rate of 1 pulse/s. After in vivo electroporation (3 wk), BAT was resected, sliced (1 mm), and mounted on a glass slide. EGFP florescence was observed with a reflection fluorescence microscope (Olympus model IX71).

RT-PCR, Northern blot, and immunohistochemistry. Total RNAs from mice BAT were prepared using an RNeasy Mini Kit (QIAGEN, Valencia, CA). RNAs (10 µg) were reverse transcribed with Rous-associated virus RT (Takara Shuzo, Shiga, Japan) at 42°C for 60 min in a 50-µl mixture in the presence of random primer. One microliter of the mixture was amplified by PCR. PCR primers used were as follows: rat TSHR, sense 5'-AAGCTGGATGCTGTTTACT-3' and antisense 5'-CACATCAAAGACTCTAGG A-3' [this set of primers specifically amplify rat TSHR, but not mouse TSHR (1)]; mouse uncoupling protein (UCP)-1, sense 5'-GG TCAAGATCTTCTCAGCCG-3' and antisense 5'-AGGCAGACCGCTGTACAGT T-3' (9); and mouse actin, sense 5'-CGTAAAGACCTCTATGCCAA-3' and antisense 5'-TGCGCAAGTTAGGTTTTGTC-3' (21). Northern blot analysis was carried out using 1 µg of mRNA purified by Oligotex-dT30 (Takara Shuzo), as described previously (4). 32P-labeled rat TSHR, mouse UCP-1, and actin cDNAs were used as probes. Immunohistochemistry of paraformaldehyde-fixed paraffin-embedded sections was carried out with ABC staining systems (Santa Cruz Biotechnology, Santa Cruz, CA). Anti-UCP-1 antibody purchased from Sigma-Aldrich Chemical (St. Louis, MO) was used as the first antibody.


   RESULTS AND DISCUSSION
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 ABSTRACT
 MATERIALS AND METHODS
 RESULTS AND DISCUSSION
REFERENCES
 
We exposed Tshrhyt/hyt and wild-type mice to a cold environment (4°C) and measured time-dependent changes of their rectal temperature. Rectal temperature of the wild-type (n = 6) and Tshrhyt/hyt (n = 6) mice before exposure to cold was 38.3 ± 0.11°C and 35.8 ± 0.18°C, respectively, the latter being significantly lower than the former (P < 0.001). After 90 min exposure to cold, the temperature of the wild-type mice slightly decreased to 37.0 ± 0.15°C, but that of the Tshrhyt/hyt mice rapidly dropped to 23.9 ± 0.40°C.

We then carried out functional rat TSHR gene transfer in the BATs by plasmid injection combined with electroporation. At first, we evaluated electroporation efficiency of DNA in the BAT of wild-type C.RF mice using EGFP expression plasmids. After in vivo electroporation (3 wk), we could observe speckled EGFP fluorescence driven by CMV promoter in the tissue but not when we used a promoterless pEGFP-1 plasmid (Fig. 1, Aa and Ab). The green fluorescent protein-positive area was 13.3 ± 2.5% of the total area (n = 4). Northern blot analysis showed a faint 0.8-kb transcript of EGFP, the amount of which was much less than that of β-actin (Fig. 1Ac).


Figure 1
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  		Fig. 1. Effects of thyroid-stimulating hormone receptor (TSHR) gene transfer on rectal temperature and brown adipose tissue (BAT) weight. A: in vivo electroporation of pCMV-EGFP in BAT. pCMV-EGFP-1 (a) and a promoterless pEGFP-1 (b) were transferred into BAT by plasmid injection combined with electroporation. After 3 wk, the tissues were resected and sliced, and their fluorescence intensity was observed. Bars indicate 1 mm. c: Northern blot analysis of EGFP. mRNA from BAT transfected with pEGFP-1 (1) or with pCMV-EGFP-1 (2) was detected by 32P-EGFP cDNA. Black and blue arrows indicate 0.8-kb EGFP and β-actin mRNAs, respectively. B: time-dependent changes of rectal temperature of the mice. The wild-type mice transfected with pcDNA3.1/Zeo (bullet, n = 7) and Tshrhyt/hyt mice transfected with pcDNA3.1/Zeo ({blacksquare}, n = 6) or with pcDNA3.1/Zeo-rat TSHR ({triangleup}, n = 6) were exposed to 4°C and then their rectal temperature was monitored every 30 min. C: a, Northern blot analysis of TSHR in BAT. mRNAs from BAT of the wild-type (1), Tshrhyt/hyt (2), Tshrhyt/hyt + rat TSHR (3), and from the liver of the wild-type (4) mice were detected with 32P rat TSHR cDNA. Black arrow and red arrow indicate 4.2-kb mouse endogenous TSHR transcripts and 2.4-kb transcripts from pSG5-rat TSHR plasmid, respectively. Lower bands are β-actin. b: RT-PCR analysis of rat TSHR mRNA from BAT. 1) Wild type mice transfected with pcDNA3.1/Zeo and 2) Tshrhyt/hyt mice transfected with pcDNA3.1/Zeo-rat TSHR (3) Tshrhyt/hyt mice transfected with pcDNA3.1/Zeo (D). BAT weight (mg)/whole body (g) x 103 is indicated. Wild, wild-type mice transfected with pcDNA3.1/Zeo; Tshrhyt/hyt, Tshrhyt/hyt mice transfected with pcDNA3.1/Zeo; Tshrhyt/hyt + rat TSHR, Tshrhyt/hyt mice transfected with pcDNA3.1/Zeo-rat TSHR; CMV, cytomegalovirus; EGFP, enhanced green fluorescent protein. *P < 0.001 and **P < 0.01.

 
Next, we transfected pcDNA3.1/Zeo in BAT of wild-type mice (n = 7) and Tshrhyt/hyt mice (n = 6) and pcDNA3.1/Zeo-rat TSHR in BAT of Tshrhyt/hyt mice (n = 6). Later (3 wk), those mice were also exposed to a cold environment (4°C). Rectal temperature of the wild-type and Tshrhyt/hyt mice before exposure to cold was 38.4 ± 0.17°C and 35.2 ± 0.15°C, respectively, the latter being significantly lower than the former (P < 0.001). After 90 min exposure to cold, the temperature of the wild-type mice slightly decreased to 36.5 ± 0.38°C, but that of the Tshrhyt/hyt mice rapidly dropped to 24.0 ± 0.40°C. Rectal temperature of Tshrhyt/hyt mice transfected with rat TSHR (rTSHR) cDNA [Tshrhyt/hyt + rTSHR mice, (n = 6)] was 37.1 ± 0.22°C, which was significantly higher than that of Tshrhyt/hyt mice (P < 0.001). Furthermore, even after a 90-min exposure to 4°C, temperature remained at 34.6 ± 0.34°C (Fig. 1B). Figure 1Ca shows the results of Northern blot analysis of TSHR in the wild-type and Tshrhyt/hyt C.RF mice. Because Roselli-Rehfuss et al. detected the TSHR message in BAT from guinea pig (18), we could also detect TSHR mRNA (4.2 kb) in BAT from the wild-type mouse, the levels of which were nearly the same as those from Tshrhyt/hyt mice. In BAT from Tshrhyt/hyt + rTSHR mice, we could detect a faint but definite 2.4-kb transcript from pcDNA3.1/Zeo-rat TSHR. By RT-PCR, we could amplify rat TSHR cDNA only from Tshrhyt/hyt + rTSHR mice, not from the wild-type and Tshrhyt/hyt mice (Fig. 1Cb).

Figure 1D shows the weight ratio of the BAT to the whole body (BAT/BW x 103) in these three groups. BAT of Tshrhyt/hyt are very atrophic. BAT/BW of the wild-type and Tshrhyt/hyt mice is 6.7 ± 0.3 and 3.2 ± 0.2, respectively. In contrast, BAT/BW of the Tshrhyt/hyt + rTSHR mice is 4.7 ± 0.4, indicating that BAT relative weight is increased, not only maintained.

Serum free T4 levels of the wild-type mice were 1.47 ± 0.09 ng/dl (n = 7). The values of Tshrhyt/hyt and Tshrhyt/hyt + rTSHR mice were 0.10 ± 0.02 ng/dl (n = 6) and 0.092 ± 0.02 ng/dl (n = 6), respectively (Table 1). No significant difference was observed between the latter two groups. At the start of this experiment, the height of Tshrhyt/hyt mice was significantly shorter than that of wild-type mice. However, no difference was observed in body weight between the groups (Table 1). These results suggest that the increase of the rectal temperature in Tshrhyt/hyt + rTSHR mice in a cold environment was not due to the difference in serum T4 levels or in animal surface area but the result of transfected functional TSHR in BAT.


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  		Table 1. Body mass of C.RFhyt/hyt mice and serum-freeT4 and cAMP T4 contents in BAT

 
Figure 2 Aa is the result of Northern analysis for UCP-1 mRNA in the wild-type, Tshrhyt/hyt, and Tshrhyt/hyt + rTSHR mice. When compared with the wild-type mice, it is evident that the expression of UCP-1 in the BAT of Tshrhyt/hyt mice was suppressed. However, UCP-1 mRNA in BAT from Tshrhyt/hyt + rTSHR mice increased about threefold compared with that of Tshrhyt/hyt mice. Figure 2, B–D, shows the results of immunostaining UCP-1 in those BAT. Adipose cells of the wild-type mice accumulated fat droplets and were strongly positive for UCP-1 (Fig. 2B). In the cells of Tshrhyt/hyt mice, however, fat droplets almost completely disappeared, and UCP-1 antibody did not stain the cells (Fig. 2C). In adipose cells of Tshrhyt/hyt + rTSHR mice, small amounts of fat droplets were observed, and UCP-1-positive speckled areas were located in these tissues (Fig. 2D).


Figure 2
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  		Fig. 2. Effects of TSHR gene transfer on uncoupling protein (UCP)-1 expression in BAT. A: Northern blot analysis of mouse UCP-1 mRNA from BAT. mRNA from the wild-type rat (1), Tshrhyt/hyt + rat TSHR (2), and Tshrhyt/hyt mice (3). Lower bands are β-actin. B-E: immunoreactivity of UCP-1 after 3 wk of in vivo electroporation of pcDNA3.1/Zeo to the wild-type mice (B, magnification x400), to the Tshrhyt/hyt mice (C, x400), and pcDNA3.1/Zeo-rat TSHR to the Tshrhyt/hyt mice (D, x400; E, x100). Arrows indicate the specked UCP-1-positive areas in BAT. Yellow bars: 100 µm, blue bar: 400 µm.

 
Finally, we supplied exogenous thyroid hormone to Tshrhyt/hyt mice. Serum-free T4 levels (1.64 ± 0.05 pg/ml) were nearly the same as those of the wild-type mice (1.51 ± 0.1 pg/ml), and rectal temperature after a 90-min exposure to 4°C (36.8 ± 0.10°C) reached that of the wild-type mice (Fig. 3). This suggests that TSH/TSHR play important roles in BAT thermogenesis when mice are in a hypothyroid state.


Figure 3
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  		Fig. 3. Changes of rectal temperature of Tshrhyt/hyt mice exposed to cold (4°C). Wild-type (bullet, n = 6) and Tshrhyt/hyt ({blacksquare}, n = 6) mice were exposed to a cold environment (4°C), and time-dependent changes in their rectal temperature were measured. Tshrhyt/hyt mice supplemented with exogenous thyroxine (T4) for 3 wk ({circ}, n = 10) were also exposed to cold.

 
BAT is the primary site of adaptive thermogenesis, heat production in response to lowering temperature, in small animals. This thermogenic capacity of BAT largely depends on UCP-1, which can dissipate the proton gradient across the inner mitochondrial membrane (13). Responsive elements for thyroid hormone and cAMP (CRE) have been identified in the 5'-flanking region of UCP-1 gene, and both catecholamines and thyroid hormone positively regulate the expression of UCP-1 gene (15, 16). Adaptive thermogenesis of BAT has been thought to be initiated by catecholamines but must have thyroid hormone present (8, 17). In the present study, we demonstrate that in vivo electroporation of functional TSHR in BAT of Tshrhyt/hyt mice did not affect the serum T4 level; alternatively, it increased UCP-1 expression, which partially restored rectal temperature of the mice. Because T3 content levels in BAT from Tshrhyt/hyt and Tshrhyt/hyt + rTSHR mice were nearly the same, but cAMP content in BAT from Tshrhyt/hyt + rTSHR mice was significantly higher than those from Tshrhyt/hyt (Table 1), it is likely that TSH/TSHR stimulated UCP-1 expression via CRE.

Human TSH/TSHR has been reported to play important roles in lipolysis in neonatal periods (11, 22). We previously reported TSH-induced lipolysis in isolated rat fat cells (7). The data presented here indicate that TSHR is involved in the regulation of thermogenesis in mouse BAT, which functions to protect a further drop in body temperature of hypothyroid mice.

A controversy exists concerning the physiological significance of BAT in humans. There is, however, a large amount of evidence to suggest BAT is present in young infants and in adults with certain pathological and nonpathological situations (2, 14), where its functions are closely related to food intake, energy expenditure, and control of body weight. Further study is needed to clarify the roles of TSHR in humans, but the present data suggest that TSH and thyroid hormone might contribute to the control of energy expenditure and metabolic rate.


   FOOTNOTES
 

Address for reprint requests and other correspondence: T. Endo, Third Dept. of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, Univ. of Yamanashi, Chuo City, Yamanashi, 409-3898, Japan (e-mail: endot{at}yamanashi.ac.jp)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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 ABSTRACT
 MATERIALS AND METHODS
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 REFERENCES
 

  1. Akamizu T, Ikuyama S, Saji M, Kosugi S, Kozak C, McBride OW, Kohn LD. Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies. Proc Natl Acad Sci USA 87: 5677–5681, 1990.[Abstract/Free Full Text]
  2. Bouillaud F, Villarroya F, Hentz E, Raimbault S, Cassard AM, Ricquier D. Detection of brown adipose tissue uncoupling protein mRNA in adult patients by a human genomic probe. Clin Sci (Lond) 75: 21–27, 1988.[Medline]
  3. Davies T, Marians R, Latif R. The TSH receptor reveals itself. J Clin Invest 110: 161–164, 2002.[CrossRef][Web of Science][Medline]
  4. Endo T, Ohta K, Haraguch K, Onaya T. Cloning and functional expression of a thyrotropin receptor cDNA from rat fat cell. J Biol Chem 270: 10833–10837, 1995.[Abstract/Free Full Text]
  5. Green RP, Birkenmeier EH, Beamer WG, Maltais LJ, Gordon JI. The hypothyroid (hyt/hyt) mouse: a model system for studying the effects of thyroid hormone on developmental changes in gene expression. Proc Natl Acad Sci USA: 85: 5592–5596, 1998.[CrossRef]
  6. Gu WX, Du GG, Kopp P, Rentoumis A, AlbaneseC, Kohn LD, Madison LD, Jameson JL. The thyrotropin (TSH) receptor transmembrane domain mutation (Pro556-Leu) in the hypothyroid hyt/hyt mouse results in plasma membrane targeting but defective TSH binding. Endocrinology 136: 3146–3153, 1995.[Abstract]
  7. Haraguchi K, Shimura H, Lin L, Endo T, Onaya T. Differentiation of rat preadipocytes is accompanied by expression of thyrotropin receptors. Endocrinology 137: 3200–3205, 1996.[Abstract]
  8. Ikemoto H, Hiroshige T, Itoh S. On possible mechanisms in an increased heat production in adipose tissues of the rat. Jpn J Physiol 15: 293–305, 1969.
  9. Jacobsson A, Stadler U, Glotzer MA, Kozak LP. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem 260: 16250–16254, 1985.[Abstract/Free Full Text]
  10. Kohn LD, Shifrin S. Receptor structure and function: an exploratory approach using the thyrotropin receptor as a vehicle. Horiz Biochem Biophys 6: 1–42, 1982.[Medline]
  11. Marcus C, Ehrén H, Bolme P, Arner P. Regulation of lipolysis during the neonatal period. Importance of thyrotropin. J Clin Invest 82: 1793–1797, 1988.[Web of Science][Medline]
  12. Morreale de Escobar G, Calvo R, Escobar del Rey F, Obregón MJ. Thyroid hormones in tissues from fetal and adult rats. Endocrinology 134: 2410–2415, 1994.[Abstract/Free Full Text]
  13. Nichols D, Locke RM. Thermogenic mechanisms in brown fat. Phyol Rev 64: 1–64, 1984.
  14. Oberkofler H, Dallinger G, Liu YM, Hell E, Krempler F, Patsch W. Uncoupling protein gene: quantification of expression levels in adipose tissues of obese and non-obese humans. J Lipid Res 38: 2125–2133, 1977.
  15. Rabelo R, Schifman A, Rubio A, Sheng X, Silva JE. Delineation of thyroid hormone-responsive sequences within a critical enhancer in the rat uncoupling protein gen. Endocrinology 136: 1003–1013, 1995.[Abstract]
  16. Rabelo R, Reyes C, Schifman A, Silva JE. Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology 137: 3478–3487, 1996.[Abstract]
  17. Ribeiro MO, Lebrun FL, Christoffolete MA, Branco M, Crescenzi A, CarvalhoSD, Negrao N, Bianco AC. Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat. Am J Physiol Endocrinol Metab 279: E314–E322, 2000.[Abstract/Free Full Text]
  18. Roselli-Rehfuss L, Robbins LS, Cone RD. Thyrotropin receptor messenger ribonucleic acid is expressed in most brown and white adipose tissues in the guinea pig. Endocrinology 130: 857–1861, 1992.
  19. Rubio A, Raasmaja A, Maia AL, Kim KR, Silva JE. Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'-monophosphate generation. Endocrinology 136: 3267–3276, 1995.[Abstract]
  20. Stein SA, Oates E, Hall CR, Grumbles RM, Fernandez LM, Taylor NA, Puett D, Jin S. Identification of a point mutation in the thyrotropin receptor of the hyt/hyt hypothyroid mouse. Mol Endocrinol 8: 129–138, 1994.[Abstract/Free Full Text]
  21. Tokunaga K, Taniguchi H, Yoda K, Shimizu M, Sakiyama S. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal beta-actin mRNA (Abstract). Nucleic Acids Res 25: 2829, 1986.
  22. Vízek K, Rázová M, Melichar V. Lipolytic effect of TSH, glucagon and hydrocortisone on the adipose tissue of newborns and adults in vitro. Physiol Bohemoslov 28: 325–331, 1979.[Web of Science][Medline]



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