Pretranslational regulation of type I 5'-deiodinase by thyroid hormones and in fasted and diabetic rats.

Abstract

In both humans and experimental animals, nutritional deprivation and systemic illness are associated with decreases in circulating T3 levels, T3 production, and type I 5'-deiodinase (5'DI) activity. In order to assess the regulation of 5'DI messenger RNA (mRNA) in these conditions, a solution hybridization assay was developed which utilized a complementary (cDNA) encompassing 92% of the 5'DI coding region. The administration of T3 to hypothyroid rats induced a 50-fold increase in 5'DI mRNA levels that preceded by 12 h a similar increase in 5'DI activity. Fasting for 48-72 h, but not 24 h, was associated with an approximate 50% decrease in 5'DI mRNA levels in liver, which preceded a decrease of similar magnitude in 5'DI activity. Fasting in hyperthyroid rats did not lower hepatic 5'DI mRNA levels or activity, nor did fasting attenuate the stimulatory effects of T3 administration on these parameters. In diabetic animals 5'DI mRNA levels and activity were markedly reduced. These results demonstrate that regulation of 5'DI by thyroid hormones and in fasting and diabetes mellitus is exerted principally at the pretranslational level. The relatively late occurrence of decreases in 5'DI mRNA levels and activity observed in nutritional deprivation suggests that these changes are secondary to, rather than causative of, the decreased serum and tissue T3 levels noted in these conditions.