Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, C100
Glucocorticoid-induced changes in liver metabolism during mouse pregnancy.
J. K. Jellyman1, E. K. Glover1, O. R. Vaughan1, A. N. Sferruzzi-Perri1, A. L. Fowden1
1. Physiology, Development and Neuroscience, University of Cambridge, Cambrigde, United Kingdom.
Glucocorticoids (GCs) are used in pregnant women world-wide for treating disorders, such as asthma. This type of treatment is known to affect fetal metabolic development, but little is known about its metabolic effects on the mother. This study examined the effects of exposure to natural and synthetic GCs on hepatic insulin signalling and glycogen concentrations in pregnant mice. All experiments were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986. Pregnant mice were divided into 3 groups: untreated controls (CT) and 2 GC-treated groups given either corticosterone (Cort; 76 μg/g/day) or dexamethasone (Dex; 200 ng/g/day) in their drinking water for 5 days prior to tissue collection on either day 16 (D16) or 19 (D19) of pregnancy. After protein extraction and standardization, the abundance of insulin receptor (IR), insulin-like-growth factor 1 receptor (IGF-1R), total Akt (Akt), phophorylation of Akt at Ser473 (pAkt), glycogen synthase kinase alpha (GSK-3α) and beta (GSK-3β) subunits and phosphorylation of the GSK-3 subunits (pGSK-3α,pGSK-3β) were measured by Western Blotting. Hepatic glycogen content was measured enzymatically. Data were analysed by two-way ANOVA, with age and treatment as factors. There were no differences in protein expression of IR, IGF-1R, GSK-α or GSK-β with age or treatment. Akt abundance was significantly lower at D19 than at D16 in controls and was significantly lower in Dex than CT dams at both ages (Table 1). PAkt expression did not change with age. In Cort and Dex dams, pAkt expression was significantly higher than CTs at D16 but not D19 (Table 1). PGSK-3α and PGSK-3β did not differ with age in CT or Cort dams (Table 1). At D16 the expression of pGSK-3α and β was significantly higher in Cort and Dex than CT dams, an effect that persisted to D19 in Cort dams only (Table 1). Hepatic glycogen content was unaffected by treatment at D16 but was lower in both Cort and Dex groups than CTs at D19. It decreased with age in Dex dams only (Table 1). These data show that GC treatment alters insulin signaling and decreases glycogen storage in the liver of pregnant mice during late gestation. This has implications for maternal metabolism and the supply of nutrients to the fetus, which may consequences long after cessation of treatment.
Where applicable, experiments conform with Society ethical requirements