Fetal exposure to synthetic
glucocorticoids in sheep results in increased fetal hepatic
11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and
corticosteroid-binding globulin (
CBG)
protein levels and
insulin resistance in postnatal life. The aim was to determine whether these changes persisted to adulthood and whether alterations in mediators of hepatic
glucocorticoid and
glucose regulation contributed to changes in metabolism. Pregnant ewes or their fetuses received either repeated intramuscular saline (MS, FS) or
betamethasone injections (0.5 mg/kg; M4, F4) at 104, 111, 118, and 124 days of gestation (dG), or a single
betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG (M1, F1). Offspring were catheterized at 2 and 3 yr of age and given an intravenous
glucose challenge (0.5 mg/kg). Hepatic tissue was collected at 3.5 yr. At 2 yr of age, basal plasma
insulin was elevated in M4 offspring and at 3 yr of age was elevated in F4 offspring. Basal
insulin-to-
glucose ratio was significantly elevated in M4 offspring at 2 yr of age and elevated in M1, M4, and F4 offspring at 3 yr of age. All
betamethasone treatments resulted in significant increases in hepatic
glucose-6-phosphatase (G-6-Pase) activity. Hepatic
glucocorticoid receptor protein levels were not altered in M1 and M4 offspring but were increased in F1 and F4 offspring. Hepatic
CBG protein levels were lower in F4 but not F1 offspring and were unchanged from control in M1 and M4 offspring. Prenatal
betamethasone exposure results in elevated hepatic G-6-Pase activity in adulthood and may contribute to long-term changes in metabolism.