title: TSH effects on thermogenesis in rat brown adipocytes.
abstract: TSH receptor (TSHR) is present in the thyroid and other tissues, as adipose tissue. In brown adipose tissue (BAT) TSH increases UCP1 expression and lipolysis. We have studied the regulation of Tshr mRNA expression and the effect of TSH on Ucp1 and Dio2 mRNA, on D2 activity and O2 consumption in rat brown adipocytes and the TSH signaling pathways. Tshr increased during brown adipocyte differentiation, was up-regulated by insulin and low TSH concentrations and down-regulated by high TSH concentrations, T3 and/or NE. TSH increased basal Ucp1 mRNA in a dose-dependent way acting synergistically with T3, while had no effect when NE was present. High TSH concentrations increased basal Dio2 mRNA (12-fold) and were synergistic with T3 (100-fold), but decreased Dio2 mRNA in T3+NE-treated cells. TSH increased D2 activities in T3-treated cells and inhibition of ERK pathway decreased the TSH effect by 55%. In T3+NE treated-cells TSH decreased D2 activity by 50%, in a dose-dependent manner. TSH activated Akt and Erk phosphorylation, while inhibition of PKA promoted Akt phosphorylation. TSH inhibited leptin mRNA. TSH increased O2 consumption by 20% and T3 enhanced its effect. Tshr is expressed in brown adipocytes and is regulated by insulin, TSH, T3 and NE. TSH increases basal and T3-stimulated Ucp1 and Dio2 expression and D2 activity only when T3 is present, but decreases Dio2 mRNA and D2 activity stimulated by NE+T3. TSH increases O2 consumption, confirming the role of TSH in the maintenance of thermogenesis.
authors: Instituto de Investigaciones Biomedicas (IIB), Centro mixto "Alberto Sols" (CSIC-UAM), Madrid, Spain.
authors: Raquel
authors: R
authors: Martinez-deMena
authors: Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.
authors: Andrea
authors: A
authors: Anedda
authors: Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain; Centro de Biología Molecular "Severo Ochoa" (CBMSO, CSIC-UAM) and Departamento de Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain.
authors: Susana
authors: S
authors: Cadenas
authors: Instituto de Investigaciones Biomedicas (IIB), Centro mixto "Alberto Sols" (CSIC-UAM), Madrid, Spain. Electronic address: mjobregon@iib.uam.es.
authors: Maria-Jesus
authors: MJ
authors: Obregon
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics; D020738:Leptin / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007328:Insulin; D007453:Iodide Peroxidase; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C000604373:Ucp1 protein, rat
keywords: BAT; Deiodinase D2; TSH; UCP1