Dietary energy restriction in the SENCAR mouse: Elevation of glucocorticoid hormone levels but no change in distribution of glucocorticoid receptor in epidermal cells

Abstract

The purpose of this study was to demonstrate that dietary energy restriction elevates plasma glucocorticoid hormone (GCH) levels while maintaining a circadian profile. Furthermore, we indirectly measured the effect of energy restriction on receptor activation in epidermis by determining the cellular localization of receptor protein in control-fed and energy-restricted (ER) mice. SENCAR mice were maintained on an ad libitum control diet or an ER diet that provided 60% of the total energy consumed by control-fed mice. Plasma corticosterone levels were determined by radioimmunoassay. Glucocorticoid receptor (GR) protein levels in epidermal lysates were measured by western blotting. Electron microscopy was used to identify gold-conjugated immunoreactive GR in epidermal cells of the skin in control and ER mice. Plasma corticosterone levels in ER mice were significantly increased 10 times over the levels in control mice at 0700 h, significantly increased two times over control levels at 1600 h, and not different from controls at 2300 h in the circadian cycle. The total amount of epidermal GR protein in ER mice was 140% (95% confidence interval, 104-169%) of that in controls at the early time point, not different at the midpoint, and 60% (95% confidence interval, 48-79%) of that in controls at the late time point. The distribution of gold-conjugated GR in the cytoplasmic and nuclear compartments of epidermal cells was similar in control and ER mice. Thus, we showed that dietary ER increased the level of plasma GCH without abolishing diurnal variation. However, an increase in ligand activation in epidermal cells, as indicated by nuclear localization of GR protein, was not supported by the results of this study.