MODULATION OF FETAL AND PLACENTAL METABOLIC PATHWAYS IN RESPONSE TO MATERNAL THYROID AND GLUCOCORTICOID HORMONE EXCESS

Triiodothyronine (T-3) treatment of pregnant rats for 6 days, 10 mu g/ 100 g, resulted in a pronounced induction of enzymes related to glucon eogenesis and lipogenesis and of mitochondrial FAD-glycerophosphate de hydrogenase in the maternal liver, as previously observed in male rats . There was virtually no change in the activiy of these enzymes in the placenta. However, there was a distinct induction of these enzymes in the fetal liver, even if increments in fetal serum and liver T-3 were much smaller than on the maternal side. This indicates that changes i n hepatic enzyme activities are a more sensitive index of fetal hypert hyroidism than T-3 levels. The increased lipogenic capacity was expres sed by greater incorporation of a tritium tracer into fatty acids. Adm inistration of triamcinolone, 2 mg/100 g, for the last 5 days of gesta tion resulted in marked induction of maternal hepatic enzymes of lipog enesis, gluconeogenesis and of aspartate aminotransferase (ASAT), know n to occur in male rats, as well as in a metabolic pattern of insulin resistance. The response of placental enzymes was limited to a small e levation in ASAT and phosphoenolpyruvate carboxykinase (PEPCK) activit y. In the fetal liver there was no stimulation of lipogenic enzymes, b ut a marked induction of PEPCK and ASAT. The changes in the lipogenic capacity were confirmed by tritium incorporation into serum and liver fatty acids. These results demonstrate the marked sensitivity of speci fic fetal enzyme systems to the maternal iatrogenic hyperthyroidism or hypercorticism. The limited alterations in placental enzyme activitie s are in accord with the concept that placental metabolic stability fu lfils a protective function toward the fetus.