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Thyroid Hormone Regulation of Thyrotropin α- and β-Subunit Gene Transcription

1985; Mary Ann Liebert, Inc.; Volume: 4; Issue: 4 Linguagem: Inglês

10.1089/dna.1985.4.301

2331-4672

James A. Gurr, IONE A. KOURIDES,

Growth Hormone and Insulin-like Growth Factors

We studied the effect of thyroid hormone on the transcription of the genes for the α- and β-subunits of thyrotropin (TSH) in thyrotropic tumors (IAK 109D and 109F) carried in hypothyroid mice. Gene transcription was measured in isolated nuclei by allowing completion of RNA chains initiated in vivo in the presence of [α-32P]UTP and by hybridization of labeled RNA transcripts to filter-bound plasmids containing α or TSH-β cDNA sequences. Treatment of animals carrying tumor IAK 109D with 3,5,3′-triiodo-l-thyronine (T3) (5 μg/100 g body weight) for 2 hr reduced TSH-β gene transcription to <10% of control levels, whereas a RNA synthesis was reduced to 59% of control. The inhibition of TSH-β gene activity was maintained after 6 hr of T3 treatment, whereas α gene transcription rose slightly to 77% of control. The tumor content of α and TSH-β mRNA, determined by dot blot hybridization with 32P-labeled plasmid probes containing α or TSH-β cDNAs, was unchanged after 2 hr of T3 treatment, and each was reduced by approximately 25% at 6 hr. These untreated tumors contained approximately equal amounts of α and TSH-β mRNA. However, the basal rate of TSH-β gene transcription was threefold greater than that of a gene transcription. Treatment of animals bearing tumor IAK 109F with the same dose of T3 for 30 min did not significantly affect a or TSH-β gene transcription, but at 2 hr α and TSH-β RNA synthesis had decreased to 50% and 10% of control values, respectively. At 12 hr, α gene transcription had returned to control levels, but suppression of TSH-β gene transcription was maintained. The content of α and TSH-β mRNA had decreased discordantly by 12 hr to 45% and 27% of control levels, respectively. In these untreated tumors α mRNA exceeded TSH-β mRNA content by about fivefold. Nevertheless, the basal rate of TSH-β transcription was 1.5-fold greater than that of α. Our studies show that T3 exerts a discordant effect on α and TSH-β gene transcription and that the effect on TSH-β RNA synthesis is much more marked. Moreover, the data suggest that, in addition to control at the level of transcription, differences in the turnover rates of α and TSH-β mRNA or nuclear RNA precursors may play a role in determining tumor α and TSH-β mRNA and protein levels.