Thyroid hormone receptor beta1 gene expression is increased by Dexamethasone at transcriptional level in rat liver.
Triiodothyronine (T3) exerts most of its effect through nuclear thyroid hormone receptors (TR) which bind mainly as heterodimers with retinoid-X receptors (RXR) to thyroid hormone response elements (TRE) in target genes. It is well known that the synergistic interaction of T3 and glucocorticoids has a role on the synthesis of growth hormone in rat pituitary cell lines and in the T3-induced metamorphosis in amphibians. Glucocorticoids increased mRNAs of T3-regulated hepatic genes. Our laboratory reported increased specific metabolic actions of T3 in rat liver by Dexamethasone (Dex) through a mechanism involving an up-regulation of the maximal binding capacity of TR. In this study we further explored the participation of TR in the molecular mechanism of the Dex-induced increase on liver T3-specific metabolic action. Dex administration to adrenalectomized rats induced an increase of liver TRbeta1 protein and mRNA. Nuclear run-on assay revealed that Dex up-regulated the TR gene transcriptional rate. Transfection assay in COS-7 cells indicated that Dex increased the transcriptional activity of the TRbeta1 promoter. Electrophoretic mobility shift assay demonstrated that Dex induced the binding of additional proteins related to or neighboring the DNA sequence of a glucocorticoid receptor (GR) binding (GRE) half-site in the TRbeta1 promoter. Evidences for an interaction of GR on the TRbeta1 promoter have been obtained. Moreover, the specificity of the GR binding to GRE was determined not only by the GRE DNA sequence, but also by the interaction of the GR with other transacting factors bound to sequences flanking the GRE.
Montesinos
M M
MM
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. montesinos@mail.fcq.unc.edu.ar
Pellizas
C G
CG
Vélez
M L
ML
Susperreguy
S
S
Masini-Repiso
A M
AM
Coleoni
A H
AH
D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D037042:Thyroid Hormone Receptors beta; D003907:Dexamethasone