Relationship between dose, mode of administration and effects of triiodothyronine on two hepatic responsive enzymes

We have examined serum 3,3',5-triiodo-L-thyronine (T3) levels and the activity of two hepatic responsive enzymes [malic enzyme (ME) and alpha-glycerophosphate dehydrogenase (alpha-GPD)] in the livers of hypothyroid rats, under conditions where different doses of T3 (1 and 2.5 micrograms/100 g b.w.) were administered daily for one week either by intraperitoneal injection or by continuous infusions. In infused animals, serum T3 concentrations were constant for the whole period of treatment while in injected groups, widely oscillating diurnal levels were observed. The injection of 2.5 micrograms/100 g b.w. resulted, at the end of the treatment, in serum T3 levels which were higher than in animals receiving the same dose by infusion. No significant differences were observed when the administered dose was 1 microgram/100 g b.w. The basal levels of alpha-GPD and ME, which were markedly reduced in the livers of hypothyroid rats, were returned to normal both in infused rats (both with the dose of 1 microgram and 2.5 micrograms/100 g b.w. of T3) and in rats injected with a dose of 1 microgram/100 g b.w.). On the other hand, the dose of 2.5 micrograms/100 g b.w. when administered by injection, resulted in alpha-GPD and ME activities which were significantly higher even than those found in normal ones. The results indicate that both the diurnal T3 profile and the activity of the two hepatic T3 responsive enzymes are dependent not only on the dose but also on the administration mode.