Regulation of Two c-erbA Messenger Ribonucleic Acids in Rat GH3Cells by Thyroid Hormone

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Abstract
There is recent evidence suggesting that c-erbA is the thyroid hormone nuclear receptor, and that there may be multiple c-erbA genes. We investigated the effect of T3 on two c-erbA mRNAs present in GH3 cells. A partial cDNA was isolated from rat GH3 cells which is nearly identical (99.6% nucleotide identity) to rat c-erbA.alpha., except for a unique 3''-region corresponding to the carboxyl terminal region of the predicted protein sequence. 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.. Since nuclear T3-binding is down-regulated by T3, we hypothesized that one or both c-erbA mRNAs might be regulated by T3. GH3 cells were treated with 10 nM T3 for up to 24 h, a manipulation known to decrease nuclear T3 binding by approximately 2-fold in GH cells. Both the 6.2 kb and 2.6 kb mRNA species decreased to nearly 50% of control values at 24 h. 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.