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The regulatory effects of thyroid hormone on biosynthesis of myocardial proteins that originate from cardiac myocytes are well established. Little is known, however, of regulatory effects of thyroid hormone on interstitial proteins. In this study we examined the effects of thyroid hormone on collagen gene expression in thyroid hormone-induced myocardial hypertrophy and the response of cardiac fibroblasts to thyroid hormone in culture. Adult male Sprague-Dawley rats were treated intraperitoneally with L-thyroxin (10 micrograms/100 g body wt) for 2 hours or 1, 2, 3, 6, 12, or 14 days. Northern blot analysis of RNA from total ventricular tissue showed that after 2 hours of treatment, the abundance of mRNA for pro alpha 2(I) collagen decreased by 53% (p less than 0.05) and reached the lowest level (60% decrease, p less than 0.02) at day 1, remained diminished at day 3, and then gradually returned toward normal levels. After transient transfection of chimeric DNA containing collagen type I promoter-chloramphenicol acetyl transferase (CAT) gene into the thyroxin-treated cardiac fibroblasts, the level of CAT activity decreased significantly. Treatment of cardiac fibroblasts in culture (10 nM L-thyroxin) resulted in a 33% (p less than 0.005) decrease in the abundance of mRNA for pro alpha 2(I) collagen. The stability of the mRNA for pro alpha 2(I) collagen in cardiac fibroblasts, as measured by mRNA half-life, was slightly (16.6%) decreased by thyroid-hormone treatment. Collagen synthesis as shown by immunofluorescent staining of intracellular collagen in cultured fibroblasts and in frozen sections of myocardium was also diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

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