Inhibition of Iodothyronine 5′-Deiodinase by Iopanoic Acid Does Not Block Nuclear T3 Accumulation During Rat Fetal Development

Abstract

We studied the effect of iopanoic acid (IOP), an iodinated contrast medium, on iodothyronine 5'-deiodinase (5'D) and nuclear T3 content (nT3) in fetal tissues. In 18- and 20 day-old fetuses from control dams, nT3 was higher in interscapular brown adipose tissue (IBAT, 69 +/- 5 and 281 +/- 8 fmol/mg of DNA) than in brain (16 +/- 2 and 42 +/- 3 fmol/mg of DNA) or liver (5.6 +/- 1 and 27 +/- 2 fmol/mg of DNA). IOP administration (10 mg, twice daily) to pregnant rats on days 18 and 19 postconception significantly blocked 5'D activity in fetal IBAT and brain at day 20. Liver 5'D was not affected. The rise in nT3 was not modified by IOP treatment in IBAT, but it was enhanced in brain and liver of IOP-treated fetuses on day 20. In contrast, in adult rats, IOP treatment reduced IBAT nT3. Prolongation of IOP treatment until day 21 decreased fetal body weight on day 22 and inhibited IBAT 5'D. No change was produced in mitochondrial oxidative capacity, the subunit II of cytochrome oxidase, or uncoupling protein mRNA expression in IBAT from IOP-treated fetuses. Thus, the finding that IOP does not decrease the nT3 of fetal IBAT explains the lack of effect of IOP on uncoupling protein expression in fetuses, in contrast with the known decrease in adults. Present results also show that IOP increases nT3 in brain and liver, indicating a general incapacity of IOP to decrease nT3 in fetal tissues. It is concluded that the effects of IOP during fetal life differ from those in adults.