TSH effects on thermogenesis in rat brown adipocytes. (15th March 2015)

• Record Type: Journal Article
• Authors: Martinez-deMena, Raquel; Anedda, Andrea; Cadenas, Susana; Obregon, Maria-Jesus
• Is Part Of: Molecular and cellular endocrinology. Volume 404(2015)
• Page Start: 151
• Page End: 158
• Publication Date: 2015-03-15
• Subjects: TSH -- BAT -- Deiodinase D2 -- UCP1; Akt or PKB protein kinase B -- BAT brown adipose tissue -- BSA bovine serum albumin -- cAMP cyclic AMP -- D2 Dio2 type 2 deiodinase -- DMEM Dulbecco minimal essential medium -- DTT dithiothreitol -- ERK extracellular-signal related kinase -- FFA free fatty acid -- FRTL5 Fisher rat thyroid cell line -- HEPES 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid -- hyt/hyt hypothyroid mice with mutation in the 4th transmembrane domain of TSH receptor -- IGFI insulin growth factor I -- IgG-HRP immunoglobulin G conjugated to horseradish peroxidase -- IU international units -- Lep leptin -- NCS newborn calf serum -- NE norepinephrine -- PBS phosphate buffered saline -- PI3K phosphoinositol-3-kinase -- PKA protein kinase A -- PPAR peroxidase proliferator-activated receptor -- PTU 6-propyl-2-thiouracil -- qRT-PCR quantitative real-time PCR -- RIA radioimmunoassay -- SEM standard error of the mean -- T3 triiodothyronine -- T4 thyroxine -- TBS Tris buffered saline -- TCA trichloroacetic acid -- TSH thyrotropin -- TSHR Tshr, TSH receptor -- Tx thyroidectomized -- Ubc ubiquitin -- UCP1 Ucp1, uncoupling protein 1; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.01.028
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: Tshr is expressed in brown adipocytes and is regulated by insulin, TSH, T3 and NE. TSH increases basal and T3-stimulated Ucp1 and Dio2 mRNA and inhibits leptin mRNA. TSH increases D2 activity in T3-treated cells, inhibiting in NE+T3 treated cells. TSH activates Akt and Erk phosphorylation. TSH increases O2 consumption, confirming the role of TSH in thermogenesis. 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.