Glucocorticoid Receptor Expression Profiles in Mononuclear Leukocytes of Periparturient Holstein Cows

Cortisol-activated glucocorticoid receptors modulate cellular responses to stress by translocating from the cytosol to the nucleus and enhancing or repressing the transcription of target genes. The functional capacity of mononuclear leukocytes is inhibited in parturient dairy cows at a time when blood cortisol concentrations are high. Because the glucocorticoid receptor is autoregulatory in many cell types, the hypothesis of the current study was that glucocorticoid receptor expression by mononuclear leukocytes is altered around parturition in association with elevated blood cortisol. If true, the glucocorticoid receptor could be involved in suppressed functions of mononuclear leukocytes in parturient cows. The objectives of this study were to determine effects of parturition on lymphocyte and monocyte glucocorticoid receptor expression and to correlate expression with serum cortisol concentrations. Objectives were achieved by using fluorescence staining and flow cytometric analyses to monitor glucocorticoid receptors in peripheral blood mononuclear leukocytes collected multiple times from 13 periparturtient test cows (eight multi- and five primiparous) and 10 midgestation control cows (five multi- and five primiparous). Serum cortisol concentrations were determined by radioimmunoassay. Based on intensity of the fluorescent glucocorticoid receptor stain, parturition caused 42 and 47% reductions in lymphocyte and monocyte glucocorticoid receptor expression, respectively, compared with mean expression in corresponding cells from control cows. When mean prepartum values were compared with nadir values at parturition in the test cows, glucocorticoid receptor expression was reduced by 67% in lymphocytes and by 54% in monocytes. Mononuclear cell expression of glucocorticoid receptors was negatively correlated with serum cortisol concentrations. Results suggest that glucocorticoid receptors are down-regulated in bovine mononuclear leukocytes in association with increased adrenal secretion of cortisol at calving. It is possible that glucocorticoid receptor down-regulation is also associated with altered phenotype or function (or both) of lymphocytes and monocytes. This possibility should be substantiated because it could explain increased disease susceptibility in periparturient dairy cows.