Selective effects of neonatal hypothyroidism on monoamine oxidase activities in the rat brain.
Hypothyroidism of mild intensity was obtained with prenatal and neonatal submission of Long-Evans rats to an iodide-rich diet. Chronic daily administration of methimazole to iodide-supplemented Long-Evans pups or to iodine-deprived Charles-River rats through the first 29-30 days of age provoked severe hypothyroidism. Monoamine oxidase type A (MAO-A) and not type B (MAO-B) activity was consistently, although slightly (by approximately 20%), increased in the hypothyroid brain. Triiodothyronine (T3)-induced hyperthyroidism did not affect MAO activity. Replacement therapy with T3 did not normalize MAO-A activity in hypothyroidism. Methimazole displayed a competitive and reversible in vitro inhibition of MAO-A but not MAO-B activity. Although this effect was obtained at concentrations far higher than those estimated to reach the brain after a single injection of the goiterogen, the occurrence of accumulation processes in the metabolism-deficient hypothyroid neonate rats cannot be excluded. Thus, MAO-A activity might be either directly depressed during the goiterogenic treatment, or increased as the result of some kind of rebound effect after interruption of methimazole administration.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D007037:Hypothyroidism / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology
D007527:Isoenzymes; D014284:Triiodothyronine; D008713:Methimazole; D013385:Succinate Dehydrogenase; D008995:Monoamine Oxidase