Differential Effects of Triiodothyronine and 3,5- Dimethyl-3′-Isopropyl-L-Thyronine Treatment of Maternal Rats upon Hepatic L-Triiodothyronine Aminotransferase Activity in Fetal Rats*

Abstract

The perinatal development of the hepatic enzyme, L-triiodothyronine aminotransferase, was determined in normal Holtzman rats. Enzyme activity was measurable but low at days 17 and 18 of gestation, increased sharply from day 19 to day 21, and increased further on the 1st postpartum day. Treatment of pregnant rats with propylthiouracil (PTU) in the drinking water, either 0.1% from day 14, or 0.2% from day 9 of gestation, reduced fetal enzyme activity significantly (P < 0.005) starting on day 21 and day 20, respectively. Maternal hypothyroidism in the group receiving 0.1% PTU was documented by a fall in serum T₃ and rT₃ concentrations to undetectable levels on day 19 of gestation. Serum concentrations of T₃ and rT₃ were undetectable in newborn rats from the PTU-treated group. Treatment of pregnant rats with daily sc injections of T₃, 2.5 μg/100 g BW, starting on day 9 of gestation, increased maternal enzyme activity to the hyperthyroid range but had no effect upon fetal enzyme activity. By contrast, daily injections of 3,5-dimethyl-3′-isopropyl-Lthyronine (DIMIT), 0.45 μg/100 g BW, significantly elevated (P < 0.001) fetal enzyme activity but had no effect upon maternal enzyme activity. These data indicate that the perinatal increase in hepatic L-triiodothyronine aminotransferase activity is temporally related to the onset of function of the fetal thyroid gland. In addition, maternal PTU ingestion diminishes, and DIMIT treatment increases fetal enzyme activity late in gestation. Furthermore, the finding that the inhibition of fetal enzyme activity by PTU is completely overcome by DIMIT demonstrates the potential of this agent for therapy of fetal hypothyroidism. (Endocrinology102: 562, 1978)