title: Modulation of fetal and placental metabolic pathways in response to maternal thyroid and glucocorticoid hormone excess.
abstract: Triiodothyronine (T3) treatment of pregnant rats for 6 days, 10 micrograms/100 g, resulted in a pronounced induction of enzymes related to gluconeogenesis and lipogenesis and of mitochondrial FAD-glycerophosphate dehydrogenase in the maternal liver, as previously observed in male rats. There was virtually no change in the activity 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 T3 were much smaller than on the maternal side. This indicates that changes in hepatic enzyme activities are a more sensitive index of fetal hyperthyroidism than T3 levels. The increased lipogenic capacity was expressed by greater incorporation of a tritium tracer into fatty acids. Administration of triamcinolone, 2 mg/100 g, for the last 5 days of gestation resulted in marked induction of maternal hepatic enzymes of lipogenesis, gluconeogenesis and of aspartate aminotransferase (ASAT), known 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 elevation in ASAT and phosphoenolpyruvate carboxykinase (PEPCK) activity. In the fetal liver there was no stimulation of lipogenic enzymes, but 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 specific fetal enzyme systems to the maternal iatrogenic hyperthyroidism or hypercorticism. The limited alterations in placental enzyme activities are in accord with the concept that placental metabolic stability fulfils a protective function toward the fetus.
authors.affiliation: Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Shafrir
authors.forename: V
authors.initials: V
authors.lastname: Barash
authors.forename: R
authors.initials: R
authors.lastname: Zederman
authors.forename: R
authors.initials: R
authors.lastname: Kissilevitz
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Diamant
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism*; D005182:Flavin-Adenine Dinucleotide; D005943:Gluconeogenesis / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000187:drug effects; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000737:chemistry; D008431:Maternal-Fetal Exchange; D008930:Mitochondria, Liver / Q000201:enzymology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014221:Triamcinolone / Q000494:pharmacology*; D014284:Triiodothyronine / Q000032:analysis / Q000097:blood / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D008055:Lipids; D014284:Triiodothyronine; D005182:Flavin-Adenine Dinucleotide; D014221:Triamcinolone; D005993:Glycerolphosphate Dehydrogenase; D001219:Aspartate Aminotransferases; D010729:Phosphoenolpyruvate Carboxykinase (GTP)