Studies on the effect of chronic L-triiodothyronine (T 3) treatment on brain Na +,K +-ATPase activity in the mature rat

Abstract

Mature rats were dosed with T 3 by different routes and dose-levels at either 0.1 mg/kg for 14 days s.c. (Group A), 1 mg/kg for 3 alternative days i.p. (Group B), 5 mg/kg for 14 days p.o. (Group C), or with propylthiouracil (PTU 50 mg/day for 14 days p.o. — Group D). Measurement of cerebellar and striatal NA +,K +-ATPase activities showed that whereas Groups A, B and D were unaffected when compared with controls, there were 35–70% increases respectively in the activities of both molecular forms of the enzyme, α(+), high ouabain affinity, and α, low ouabain affinity, in Group C rat brains at the highest dose of T 3 tested. Kidney Na +,K +-ATPase activity was also elevated (67% increase) in this group of animals showing significant changes in renal medullary tissue only. Acute elevation of brain dopamine levels by administration of an MAOI plus L-DOPA (50 mg/kg, 60 min) significantly elevated (20% increase) the activities of both molecular forms of Na +,K +-ATPase in corpus striatum. Treatment with L-tryptophan (50 mg/ kg, 60 min) failed to produce any changes in the striatal activities. The possible relationship of increases in enzyme activities with T 3 and increased brain monoamine function is discussed. Both plasma free T 4(FT 4) and total T 4(TT 4) were markedly depressed in all T 3-treated rats. Although hypothalamic thyrotropin releasing hormone (TRH) concentrations were unaltered by any of the T 3 treatments, pituitary thyroid stimulating hormone (TSH) concentrations were greatly diminished and it is thought that this may reflect a direct effect of T 3 on TSH synthesis.