Corticotropin-Releasing Hormone Affects Short Immobilization Stress-Induced Changes in Lung Cytosolic and Membrane Glucocorticoid Binding Sites

Abstract

Glucocorticoids act via glucocorticoid receptors (GR), typically localized in the cytosol (cGR). Rapid action is probably mediated via membrane receptors (mGR). In corticotropin-releasing hormone knockouts (CRH-KO), basal plasma glucocorticoid levels do differ from wild type levels (WT), but are approximately ten times lower during exposure to immobilization stress (IMMO) in comparison to WT. We tested the following hypotheses: (1) the mice lung tissue GR basal numbers would not be changed in CRH-KO (because of similar glucocorticoid levels), (2) the number of GR would be changed in WT but not in KO during short (30, 90, and 120min) IMMO (because of higher increase of glucocorticoid levels in WT). The basal levels of cGR were not changed in CRH-KO (compared to WT), while mGR were significantly lower (62%) in CRH-KO. In WT, there was the only decrease (to 32%) in cGR after 120min when we also found an increase in mGR in WT (to 201%). In CRH-KO, IMMO caused gradual decrease in cGR (to 52% after 30min, to 46% after 90min, and to 32% after 120min). In CRH-KO, the only increase in mGR appeared already at 30min of IMMO. These data suggest, on the contrary to our hypotheses, that CRH-KO are more susceptible to GR changes in early phases of stress.