title: Skeletal muscle glucose transporter protein responses to antenatal glucocorticoids in the ovine fetus.
abstract: We investigated the effects of maternal antenatal dexamethasone (Dex) treatment given as a single course (4 doses) or multiple courses (20 doses) on fetal skeletal muscle glucose transporter (GLUT) protein concentrations at 70% of gestation (106 to 107 days with term being 145 to 150 days) in the ovine fetus. Antenatal corticosteroid administration was associated with a decrease in endogenous fetal plasma cortisol concentrations (P < 0.05), fetal hyperglycemia (P < 0.02) and hyperinsulinemia (P < 0.05). These metabolic/hormonal changes were associated with a decrease in fetal body weight (P < 0.05) in the multiple course Dex group compared with the multiple course placebo group. These perturbations were associated with an increase in fetal skeletal muscle GLUT 1 concentrations that mediate basal glucose transport in the extensor digitorum lateralis and extensor digitorum longus muscles (P < 0.05) 18 h after the last dose of Dex was given in the single course group. However, in the multiple course Dex group, a small increase in GLUT 1 was observed only in the biceps femoris. In contrast, both single and multiple courses of antenatal Dex were associated with an increase in the extensor digitorum lateralis and biceps femoris muscle GLUT 4 (insulin-responsive) concentrations (P < 0.05). We conclude that antenatal corticosteroids perturb fetal glucose/insulin homeostasis, which is associated with increases in fetal skeletal muscle glucose transporters to compensate for and attenuate the associated catabolic fetal state. These changes consist of an increase in proteins that mediate basal glucose transport (GLUT 1) to meet immediate energy requirements of the fetal skeletal muscle with an increase in basal insulin sensitivity (GLUT 4) to compensate for the Dex-induced catabolic state after exposure to multiple courses of Dex.
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gray
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Stonestreet
authors.forename: Shanthie
authors.initials: S
authors.lastname: Thamotharan
authors.forename: Grazyna B
authors.initials: GB
authors.lastname: Sadowska
authors.forename: Molly
authors.initials: M
authors.lastname: Daood
authors.forename: Jon
authors.initials: J
authors.lastname: Watchko
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D003907:Dexamethasone / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage*; D051246:Glucose Transport Proteins, Facilitative / Q000032:analysis*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D051275:Glucose Transporter Type 4 / Q000032:analysis; D006400:Hematocrit; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007273:Injections, Intramuscular; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000196:embryology*; D018995:Myosin Heavy Chains / Q000032:analysis; D011247:Pregnancy; D012756:Sheep
chemical_list: D005938:Glucocorticoids; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D003907:Dexamethasone; D018995:Myosin Heavy Chains; D006854:Hydrocortisone