Regulation of glucogenesis by thyroid hormones in fetal sheep during late gestation.
The effects of thyroid hormone deficiency in utero on the fetal glucogenic capacity were investigated by measuring glucose production and hepatic levels of glycogen and gluconeogenic enzymes in normal sheep fetuses in the fed and fasted states during late gestation and in those made thyroid hormone deficient by fetal thyroidectomy (TX). In the fed state, fetal TX had no effect on glucose uptake, utilisation or production by the fetus. It also had no apparent effect on the glycogen content or activities of the key gluconeogenic enzymes in the fetal liver. In addition, fetal plasma concentrations of insulin, cortisol, adrenaline or noradrenaline were unaffected by fetal TX in the fed state. In contrast, the rates of fetal O(2) consumption and CO(2) production per kilogram fetal bodyweight were significantly lower in TX than in intact fetuses in the fed state (P<0.05). TX prevented fetal glucose production in response to maternal fasting for 48 h. It also abolished the normal decreases in the fetal glucose carbon oxidation fraction, the rate of CO(2) production from glucose carbon and in the fraction of the umbilical O(2) uptake used for glucose carbon oxidation that occur during fasting in intact fetuses. At the end of the fast, plasma noradrenaline concentrations and hepatic levels of glycogen, glucose 6-phosphatase, fructose diphosphatase and alanine aminotransferase were significantly lower in TX than in intact fetuses. These observations show that thyroid hormones are essential for glucogenesis in the sheep fetus during late gestation and suggest that these hormones act both on the hepatic glucogenic pathways and on the mechanisms activating glucogenesis in utero.
Fowden
A L
AL
Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK. alf1000@cam.ac.uk
Mapstone
J
J
Forhead
A J
AJ
D000410:Alanine Transaminase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000378:metabolism* / Q000601:surgery; D005635:Fructosediphosphates / Q000378:metabolism; D005865:Gestational Age; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000032:analysis; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000196:embryology; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D010927:Placental Insufficiency / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep / Q000196:embryology*; D013963:Thyroid Hormones / Q000502:physiology*; D013965:Thyroidectomy
D005635:Fructosediphosphates; D007328:Insulin; D013963:Thyroid Hormones; D002245:Carbon Dioxide; D019298:Glucose-6-Phosphate; D006003:Glycogen; D000410:Alanine Transaminase; D005947:Glucose; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine