THYROTROPIN STIMULATES GLUCOSE-REGULATED PROTEIN (GRP78) GENE-EXPRESSION IN RAT FUNCTIONAL THYROID EPITHELIAL-CELLS, FRTL

We cloned a 1.2-kilobase cDNA (C17-16) from a transformed FRTL thyroid cell library. Northern blot analysis revealed that the size of the corresponding mRNA was 2.0 kilobases. C17-16 mRNA was found in all tissues investigated, but interestingly, its expression was 5- to 10-fold higher in the thyroid glands than in other tissues. Addition of TSH to FRTL cells showed a time- and dose-dependent increase in the steady state level of C17-16 mRNA, and the effect was mimicked by (Bu)2cAMP. An in vitro nuclear run-off assay demonstrated that the stimulatory effect was due to an increase in the transcription rate of the C17-16 gene. TSH had no effect on the half-life of the C17-16 mRNA. Transcriptional induction of the C17-16 gene was inhibited when the cells were treated with cycloheximide. Nucleotide sequencing revealed that C17-16 was identical to the cDNA of rat glucose-regulated protein (GRP78), a member of the heat shock protein family. These results suggest that the expression of GRP78 in thyroid cells is regulated by TSH via cAMP, for which cycloheximide-sensitive protein synthesis might be required, and that more GRP78 might be needed to assist in the synthesis and transport of glycoprotein molecules in TSH-stimulated cells.