Add time:07/31/2019         Source:sciencedirect.com

We have examined the effects of treatment of the rat with 3,5-dimethyl-3′-isopropyl thyronine (DIMIT) and 3,5-diethyl-3′-isopropyl thyronine (DIET) on serum thyrotropin (TSH) concentration, heart weight, hepatic outer ring (5′-) monodeiodination of T4 to T3, cardiac outer ring monodeiodination of 3′,5′-diiodothyronine (3′,5′-T2) to 3′-monoiodothyronine (3′-T1), and cerebral cortical monodeiodination of 3,5-T2 in the inner ring to 3-T1. Groups of four to seven rats were injected intraperitoneally either once a day or at eight-hour intervals for three days with saline or thyronines. Serum TSH was measured by radioimmunoassay. The various monodeiodinations were studied in homogenates of the tissues at optimal pH (7.35 for outer ring monodeiodinations and 8.0 for inner ring monodeiodination) and temperature (37 °C) in the presence of an excess of dithiothreitol. DIMIT was clearly active in all thyromimetic effects studied. It was about 10% as active as T4 in suppression of TSH. It stimulated hepatic monodeiodination of T4 to T3 in a similar manner to T4. DIMIT was also more comparable to T4 than to T3 in effect on heart weight and cardiac metabolism of 3′,5′-T2 to 3′-T1. It was highly active, apparently more so than either T4 or T3, in cerebral cortical stimulation of metabolism of 3,5-T2 to 3-T1. In distinction to DIMIT, DIET had very little thyromimetic activity. It did not significantly affect serum TSH, serum T4, or hepatic or cerebral cortical metabolism of iodothyronines in doses up to 50 μg (∼137 nmol)/100g/day; it did demonstrate, however, a significant although only a modest stimulatory effect on cardiac weight and metabolism of 3′,5′-T2. Conclusions: (1) DIMIT is clearly active whereas DIET is a very weak thyromimetic substance. (2) High activity of DIMIT in the cerebral cortex suggests that DIMIT may serve as an agent especially suited for directing thyroid hormone effects at the cerebral cortex.

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