Disease relevance of Thra

• Primary cultures of rat astrocytes, the astrocytoma cell line C6, and the pheochromocytoma cell line PC12 contained only the c-erbA alpha 2 mRNA [1].
• In addition, our data show that the c-erbA product directly activates the Moloney murine leukemia virus promoter in a ligand-dependent manner [2].
• These results indicate that hypothyroidism induced an increase in cellular c-erbA alpha 2 mRNA level in the pPVN [3].
• To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and investigated their response to thyroid hormone [4].

High impact information on Thra

• Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription [5].
• Unlike the other members of the c-erbA proto-oncogene family, which have a wide tissue distribution, r-erbA beta-2 appears to be expressed only in the anterior pituitary gland [6].
• Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone [7].
• The present work examines the molecular nature of T3 receptor autoregulation using probes specific for each c-erbA mRNA [7].
• Normal timing of oligodendrocyte development depends on thyroid hormone receptor alpha 1 (TRalpha1) [8].

Biological context of Thra

• These data indicate that these two c-erbA mRNAs are regulated by T3 and suggest that the T3 effect on T3 binding-activity in GH cells may be mediated, in part, by down-regulation of c-erbA mRNA levels [9].
• We have isolated a novel rat c-erbA cDNA, r-erbA alpha-2, identical to the rat brain c-erbA alpha cDNA (which we refer to as r-erbA alpha-1) except at the 3'-end of the cDNA, which encodes an altered carboxy-terminal region of the predicted amino acid sequence [10].
• DNA-binding studies with in vitro translated c-erbA indicate that each of the S14 TREs contains a specific binding site for the receptor [11].
• The analysis of a series of deletion and point mutants of the c-erbA-1 promoter led to the identification of an upstream region that is necessary for NS1-driven transactivation [12].
• The proto-oncogene c-erbA and its analogues are genes that encode thyroid hormone receptors [13].

Anatomical context of Thra

• Comparison of the concentrations of c-erbA alpha 1-mRNA, beta 1-mRNA, or their sum to the T3 nuclear binding capacity per mg of DNA in adult liver, kidney, heart, cerebrum, and cerebellum and during the ontogeny of liver and brain shows that the T3 binding capacity/c-erbA mRNA ratio is tissue-specific and related to developmental state [14].
• Regulation of multiple c-erbA gene expression was studied in rat thyroid FRTL-5 cells [15].
• TR beta 1, TR alpha 1 and c-erbA-alpha 2 mRNAs were detected in brown adipocytes [16].
• Developmental regulation of the thyroid hormone receptor alpha 1 mRNA expression in the rat testis [17].
• We have previously found that TR beta-1 is the major receptor form expressed in the adult rat small intestine, although there are also moderate levels of c-erbA alpha-2, a nonhormone-binding variant that is thought to inhibit T3 action [18].

Associations of Thra with chemical compounds

• c-erbA cDNAs encoding thyroid hormone-binding receptor proteins have been previously isolated from several species and tissues [10].
• The reduction of receptor caused by retinoic acid is accompanied by a decreased expression of c-erbA alpha 1 and alpha 2 mRNAs, but the retinoid did not reduce the abundance of c-erbA beta mRNA [19].
• A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit [20].
• The presence of noradrenaline, a positive control for UCP expression, increased only the level of expression of the 5.5-kb c-erbA alpha-mRNA, but values for nuclear T3-binding capacity similar to those obtained in T3-treated cells were observed [21].
• Immunohistochemical detection of c-myc and c-erbA products in diethylnitrosamine-induced preneoplastic and neoplastic liver lesions in rats [22].

Other interactions of Thra

• This cDNA (c-erbA alpha-2), like rat c-erbA alpha, hybridizes to a 2.6 kilobase (kb) mRNA which is distinct from a 6.2 kb species that hybridizes to c-erbA beta [9].
• Differential regulation of multiple c-erbA expression by thyrotropin, insulin and insulin-like growth factor I in rat thyroid FRTL-5 cells [15].
• These are encoded by two genes: c-erbA-alpha encoding TRalpha1 and TRalpha2 and their respective Delta isoforms, and c-erbA-beta which encodes TRbeta1, TRbeta2 and TRbeta3 [23].
• Rev-ErbA alpha is an approximately 56-kilodalton protein most similar in structure to the thyroid hormone receptor (c-erbA) and the retinoic acid receptor, but it does not bind either thyroid hormone or retinoic acid [20].
• Surprisingly, when the three cell types are growing at similar rates only, one protooncogene (c-mos) is not expressed at detectable levels in L6 alpha 1, two others (c-fos, c-erbA) are not expressed in M4 or in RMS4, and three additional ones (c-erbB, c-sis, c-src) are expressed in M4 but not in RMS4 [24].

Analytical, diagnostic and therapeutic context of Thra

• Immunocytochemistry using isoform-specific anti-sera revealed that TR beta 1 was exclusively localized to neuronal nuclei, and c-erbA alpha 2 was only found in the nuclei of astrocytes [1].
• Northern blot analyses reveal marked tissue-specific and differential regulation of the multiple c-erbA mRNAs by T3 [7].
• Estimation of the protein content of thyroid hormone receptor alpha 1 and beta 1 in rat tissues by western blotting [25].
• To examine thyroid hormone regulation of c-erbA alpha 2 mRNA expression in the parvo-cellular region of the paraventricular nucleus of the rat hypothalamus (pPVN), quantitative in situ hybridization was performed using 3H-labeled probe complementary to c-erbA alpha 2 mRNA [3].
• Increase in c-erbA alpha 2 mRNA in the parvocellular region of the paraventricular nucleus of the hypothalamus following thyroidectomy in the adult male rat [3].

References