The Ontogeny of Iodothyronine Deiodinase Systems in Liver and Intestine of the Rat*

Abstract

The ontogeny of the iodothyronine deiodinase systems has been studied by several investigators in recent years, but our understanding of the subject is far from complete. The present study was conducted to obtain kinetic information concerning 5' deiodinase (5'D) and 5 deiodinase (5D) activities in fetal rat liver and intestine, and to examine reduced glutathione (GSH)-activated 5'D activity in the two tissues. When dithiothreitol (DTT) was used as cofactor in concentrations up to 100 mM, 5'D activity was not clearly detected in liver or intestine until day 16 of gestation. Activity increased markedly in both tissues between fetal day 18-21, due primarily to an increase in maximum velocity (Vmax) of the enzyme. However, whereas 5'D activity was much higher in adult liver than in fetal liver [due to both an increase in Vmax and a decrease in the Michaelis-Menten constant (Km)], activity was barely detectable in adult intestine. When GSH was used as cofactor, the temporal development of activity in both tissues was comparable to that observed with DTT, but kinetic values were very different; with DTT mean values for Vmax in liver ranged from 3.7-1264 pmol I-/h.mg protein, and values for Km ranged from 0.1-0.5 microM; with GSH, values for Vmax ranged from 0.4-16.7 pmol I-/h.mg protein, and values for Km were less than 1 nM. A comparable difference was observed also in intestine. When either DTT or GSH was used as cofactor, 5'D activity was inhibited in the presence of 6n-propyl-2-thiouracil or iopanoic acid. Using T3 as substrate it was found that 5D activity was much higher in intestine than in liver, and the amount of 5D activity in intestine paralleled that in brain in that it was much higher in fetal than in adult tissue. Moreover, values for Vmax and Km in fetal intestine were comparable to those in fetal brain. These findings suggest that thyroid hormone is important in the developing rat intestine and raise the possibility that GSH could be the activator of 5'D systems in vivo.