Time course of response of individual messenger RNAs in the rat heart to T3

The time course of response of specific mRNAs following administration of triiodothyronine (T3) to hypothyroid rats was examined. We were particularly interested in identifying mRNAs showing a rapid response. Hypothyroid rats were injected with 0.2 mg of T3/100 g body wt and total cardiac RNA was prepared 0.5, 1, 2, 3, 5, 12 and 24 h later. RNA was translated in vitro in the presence of [35S]-methionine, the labeled peptides separated by two-dimensional electrophoresis and quantitated by digital matrix photometry. Of a total of 427 translational products 13 were identified to be selectively responsive to thyroid hormone. A specific mRNA coding for a protein designated as spot 72b (Mr 81,600, pI 5.34) was observed to show the most rapid response to T3. Administration of T3 to the hypothyroid animal resulted in an increase in the level of spot 72b by 2.6-fold within 1 h. The lag time between injection of T3 and response of other specific mRNA species varied between 5 to 24 h. These results demonstrate the diversity of response of individual cardiac mRNAs. The specific T3 responsive mRNA species described in the heart have not been demonstrated in other tissues indicating that induction of distinctive mRNA species is highly tissue specific. Relatively late responses may represent indirect effects of T3 mediated by interaction with other hormonal or metabolic signals. The rapid induction of spot 72b suggests it may result from the interaction of T3 with the nuclear receptor leading to a direct effect on the expression of this gene in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)