The effect of L-thyroxine on monoamine oxidase activity on various organs of the rat



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In vivo and in vitro experiments were made to investigate the effects of L-thyroxine (T[subscript 4]) on the monoamine oxidase (MAO) activity of various organs of the rat. MAO activity was measured using tryptamine, and in some experiments, kynuramine as the substrates. T[subscript 4] specifically affected the MAO activity of certain organs but not others. Liver, heart, kidney, and brain MAO showed significant changes whereas that of the vas deferens, adrenal and thyroid glands were unaffected. In vivo, T[subscript 4] (10, 30 and 300 pg/kg, for 5 days) decreased the MAO activity of the liver, raised that of the kidney, caused biphasic effects in the heart (low doses depressed but the high dose increased) and failed to alter the brain enzyme. All changes were dose-dependent. A time-course study using the 30 pg/kg dose revealed time-related changes over a period of 5 days, with the kidney being the most susceptible organ. All changes were reversible upon discontinuing treatment. Studies in hypophysectomized (HX) rats showed that T[subscript 4] (10 pg/kg) could reverse the resulting decline in kidney MAO, suggesting that this effect of hypophysectomy results from thyroid insufficiency. Kidney homogenates made from T[subscript 4] treated rats "activated" the MAO in control kidneys but no evidence for either activation or inhibition was obtained in similar experiments utilizing liver. In vitro, T[subscript 4] inhibited liver MAO and increased that of the kidney. Thus these effects paralleled those seen in the in vivo experiments. This did not hold true for brain MAO activity. T[subscript 4] greatly augmented the MAO activity of the brain when added to the crude homogenates. The extent of the increase in brain and kidney MAO was dependent upon the time of pre-incubation with T[subscript 4] and all in vitro effects were found to be concentration-related. Whereas the kidney and liver reflected changes in MAO with both tryptamine and kynuramine; tryptamine alone detected the vast increase in the activity of the brain enzyme. This suggests that only certain of the brain isoenzymes of MAO were activated by T[subscript 4]. The above findings show specific and reversible changes in MAO which were characterstic of the tissue. These changes may be connected with preferential influences of T[subscript 4] (or a metabolite) on the various isoenzymes of MAO, although other explainations are discussed. The findings also suggest that T[subscript 4] may serve as a physiological regulator of MAO, particularly in the kidney.