Propylthiouracil and alcoholic liver disease.
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The activity of rat liver malic enzyme (L-malate: NADP oxidoreductase/decarboxylating, MDH, E.C. 1.1.1.40) after T4 or T4 + alpha-amanitin treatment was investigated in relation to nuclear specific binding of T4. Specific binding of 125I-T4 to hepatic nuclear sites in rats at 21 days after thyreoparathyreoidectomy (Tx) was significantly increased (P less than 0.01) and was restored within 24 hours after a single dose of T4. Equilibrium association constants Ka estimated in all experimental groups were not attenuated. The activity of MDH increased 48 and 120 hours after a single dose of T4. In contrast, it decreased after Tx and was restored after T4 injection. The initial block of the stimulatory effect of T4 on MDH activity induced by alpha-amanitin observable during the first 48 h was overcome after 120 h when the increase of MDH activity was not only increased to normal values but reached values of T4 treated rats. It seems that the signal for the increase of the activity of MDH induced by thyroid hormones could occur as a secondary phenomenon stimulated by an as yet undefined intracellular process.
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