Effects of pharmacological and nonpharmacological treatments on thyroid hormone metabolism and concentrations in rat brain

The activities of the 5'I-deiodinase (5'D-I), 5'II deiodinase (5'D-II) and Sm-deiodinase (5D-III) isoenzymes and tissue concentrations of thyroxine (T -4) and triiodothyronine (T-3) were measured in up to 10 regions of the rat brain after acute and subchronic nonpharmacological (sleep deprivation, 12 h fasting, 14 days' calorie-reduced diet) and pharmacological (ethanol, ha loperidol, clozapine, lithium, carbamazepine, desipramine, fluoxetine, tran ylcypromine, and mianserin) treatments. All of these treatments induced sig nificant and sometimes dramatic changes in 5'D-II activities and tissue con centrations of thyroid hormones and, to a lesser extent, in 5D-III activity . The activity of 5'D-I remained unaffected. The results revealed a surpris ing specificity for each type of treatment in terms of the isoenzyme and ho rmone affected, the direction of the change, the brain region affected and the time of day. The changes in thyroid hormone concentrations frequently f ailed to correspond in any way to those in deiodinase activities and unexpe cted effects such as inhibition of both 5'D-II and 5D-III were seen, indica ting that there may be additional pathways of iodothyronine metabolism in t he CNS. In conclusion, particularly 5'D-II activity and thyroid hormone con centrations in the CNS are highly sensitive to many different kinds of infl uence that may induce changes in neuronal activity. However, these changes in deiodinase activities do not ensure stable tissue concentrations of T-3, but were, on the contrary, in most cases accompanied by marked changes T-3 levels in the tissue. The implications of these findings for the physiolog ical role of thyroid hormones in the CNS are discussed.