The effect of RanBPM on the regulation of the hypothalamic-pituitary axis by thyroid hormone receptors is isoform-specific.
Although crucial for TH homeostasis, the molecular mechanisms responsible of thyroid hormone receptors (TRs)-mediated regulation of the hypothalamic-pituitary-thyroid axis (HPT) axis remain unclear. We examined the role played by TR-isoforms in combination with RanBPM, a novel coactivator of TRs. In transient transfections studies with the human TRH and TSH-alpha subunit promoters, we found that the overexpression of RanBPM increases the transcriptional activity of all TR-isoforms by a magnitude of 1.7- to 3-fold. The addition of RanBPM, in the absence of THs, increased the ligand-independent activation (LIA) of TRalpha1 and TRbeta1 on both promoters tested by 300% and 200%, respectively, whereas, the LIA of TRbeta2 was not significantly modified. This data reinforces the concept of isoform-specific regulation of genes of the HPT axis and demonstrates that RanBPM may be an important factor to achieve adequate regulation of nTREs in the presence of low TH levels.
Poirier
Marie-Belle
MB
Department of Medicine, Division of Endocrinology, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, C.H.U.S., 3001, 12th Avenue North, Sherbrooke, Que., Canada J1H 5N4.
Brunelle
Mylène
M
Langlois
Marie-France
MF
D048868:Adaptor Proteins, Signal Transducing; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D005786:Gene Expression Regulation; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D009687:Nuclear Proteins; D020033:Protein Isoforms; C116005:Ran binding protein 9; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D020931:ran GTP-Binding Protein