Transducin β-like 1, X-linked and nuclear receptor co-‍repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors.

Transducin β-like 1, X-linked and nuclear receptor co-‍repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors. Endocr J. 2018 May 23;: Authors: Takamizawa T, Satoh T, Miyamoto T, Nakajima Y, Ishizuka T, Tomaru T, Yoshino S, Katano-Toki A, Nishikido A, Sapkota S, Watanabe T, Okamura T, Ishida E, Horiguchi K, Matsumoto S, Ishii S, Ozawa A, Shibusawa N, Okada S, Yamada M Abstract Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus-pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors (TR) in cell culture systems. We herein investigated whether TBL1X affects the unliganded TR-mediated stimulation of the promoter activities of genes negatively regulated by T3 in cooperation with N-CoR. In a hypothalamic neuronal cell line, the unliganded TR-mediated stimulation of the TRH gene promoter was significantly enhanced by co-transfected TBL1X, and the co-transfection of TBL1X with N-CoR further enhanced promoter activity. In contrast, the knockdown...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research