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1 School of Women's and Infants' Health, The University of Western Australia, Subicao, Western Australia, Australia; Women and Infants Research Foundation, Subiaco, Western Australia, Australia
2 School of Women's and Infants' Health, The University of Western Australia, Subicao, Western Australia, Australia
3 Departments of Physiology and Obstetrics and Gynecology, CIHR Group in Fetal and Neonatal Health and The University of Toronto, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: dsloboda{at}obsgyn.uwa.edu.au.
Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hepatic 11
-hydroxysteroid dehydrogenase type 1 (11HSD1) and corticosteroid binding globulin (CBG) protein levels and insulin resistance in postnatal life. Aim: to determine if 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 (0.5mg/kg; M4, F4) at 104, 111, 118 and 124 days of gestation (dG), or a single betamethasone injection at 104, followed by saline at 111, 118 and 124 dG (M1, F1). Offspring were catheterized at 2 and 3 years of age and given an intravenous glucose challenge (0.5mg/kg). Hepatic tissue was collected at 3.5 years. At 2 years of age basal plasma insulin was elevated in M4 offspring and at 3 years of age was elevated in F4 offspring. Basal insulin-to-glucose ratio was significantly elevated in M4 offspring at 2 years of age and elevated in M1, M4 and F4 offspring at 3 years of age. All betamethasone treatments resulted in significant increases in hepatic glucose-6-phosphatase (G6P) 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 G6P activity in adulthood and may contribute to long-term changes in metabolism.
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