THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF PRAIRIE VOLES (MICROTUS-OCHROGASTER) - EVIDENCE FOR TARGET TISSUE GLUCOCORTICOID RESISTANCE

Basal plasma corticosterone levels in prairie voles (Microtus ochrogas ter) are extremely high, in the absence of any apparent negative conse quences of glucocorticoid excess. We tested the hypothesis that prairi e voles are a novel rodent model of target tissue resistance to glucoc orticoids. Prairie voles had a significantly higher adrenal-to-body we ight ratio, 5- to 10-fold greater basal plasma corticosterone, and 2- to 3-fold greater basal plasma ACTH concentrations than montane voles (Microtus montanus) and rats. While plasma corticosterone binding glob ulin (CBG) was 2-fold higher in prairie voles than in rats, both estim ated and directly measured plasma free corticosterone were significant ly higher in prairie voles than in rats. Plasma corticosterone levels in prairie voles were responsive to both circadian cues and a stressor , but were resistant to suppression by the synthetic glucocorticoid, d examethasone (DEX). Western blots of brain and liver protein extracts, using a glucocorticoid receptor (GR) antibody, revealed the presence of a similar to 97 kDa immunoreactive band, the expected size for GR. Binding assays revealed significantly lower DEX affinity of corticoste roid receptors (CR) in cytosol of prairie vole brain and liver than th at in the same tissues in rats. We conclude that prairie voles are a n ovel rodent model of glucocorticoid resistance, and that decreased aff inity of CR for ligand might be partially responsible for this phenome non. (C) 1997 Academic Press.