title: Effects of dexamethasone on the glucogenic capacity of fetal, pregnant, and non-pregnant adult sheep.
abstract: Fetal glucocorticoids have an important role in the pre-partum maturation of physiological systems essential for neonatal survival such as glucogenesis. Consequently, in clinical practice, synthetic glucocorticoids, like dexamethasone, are given routinely to pregnant women threatened with pre-term delivery to improve the viability of their infants. However, little is known about the effects of maternal dexamethasone treatment on the glucogenic capacity of either the fetus or mother. This study investigated the effects of dexamethasone treatment using a clinically relevant dose and regime on glycogen deposition and the activities of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and kidney of pregnant ewes and their fetuses, and of non-pregnant ewes. Dexamethasone administration increased the glycogen content of both the fetal and adult liver within 36 h of beginning treatment. It also increased G6Pase activity in the liver and kidney of the fetuses but not of their mothers or the non-pregnant ewes. Neither hepatic nor renal PEPCK activity was affected by dexamethasone in any group of animals. These changes in glycogen content and G6Pase activity were accompanied by rises in the plasma glucose and insulin concentrations and by a fall in the plasma cortisol level in the fetus and both groups of adult animals. In addition, dexamethasone treatment raised fetal plasma tri-iodothyronine (T(3)) concentrations and reduced maternal levels of plasma T(3) and thyroxine, but had no effect on thyroid hormone concentrations in the non-pregnant ewes. These findings show that maternal dexamethasone treatment increases the glucogenic capacity of both the mother and fetus and has major implications for glucose availability both before and after birth.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Franko
authors.forename: D A
authors.initials: DA
authors.lastname: Giussani
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000032:analysis / Q000378:metabolism; D006003:Glycogen / Q000032:analysis / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000196:embryology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D023421:Models, Animal; D010730:Phosphoenolpyruvate Carboxylase / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep; D013268:Stimulation, Chemical; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D014284:Triiodothyronine; D003907:Dexamethasone; D006003:Glycogen; D005952:Glucose-6-Phosphatase; D010730:Phosphoenolpyruvate Carboxylase; D013974:Thyroxine; D006854:Hydrocortisone