Preisler M T, Weber P S, Tempelman R J, Erskine R J, Hunt H, Burton J L
Department of Animal Science, Michigan State University, East Lansing 48824, USA.
J Dairy Sci. 2000 Jan;83(1):38-47. doi: 10.3168/jds.S0022-0302(00)74852-1.
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.
皮质醇激活的糖皮质激素受体通过从细胞质转运至细胞核并增强或抑制靶基因转录来调节细胞对应激的反应。在血皮质醇浓度较高时，围产期奶牛的单核白细胞功能能力受到部分抑制。由于糖皮质激素受体在许多细胞类型中具有自我调节作用，因此本研究的假设是，围产期单核白细胞的糖皮质激素受体表达会随着血皮质醇升高而改变。如果这一假设成立，糖皮质激素受体可能参与围产期奶牛单核白细胞功能的抑制。本研究的目的是确定分娩对淋巴细胞和单核细胞糖皮质激素受体表达的影响，并将表达情况与血清皮质醇浓度相关联。通过荧光染色和流式细胞术分析来监测从13头围产期试验奶牛（8头经产牛和5头初产牛）和10头妊娠中期对照奶牛（5头经产牛和5头初产牛）多次采集的外周血单核白细胞中的糖皮质激素受体，从而实现研究目的。血清皮质醇浓度通过放射免疫测定法测定。基于荧光糖皮质激素受体染色强度，与对照奶牛相应细胞的平均表达相比，分娩分别使淋巴细胞和单核细胞糖皮质激素受体表达降低了42%和47%。当将试验奶牛产前的平均表达值与分娩时的最低点值进行比较时，淋巴细胞中糖皮质激素受体表达降低了67%，单核细胞中降低了54%。单核细胞糖皮质激素受体表达与血清皮质醇浓度呈负相关。结果表明，在奶牛产犊时，随着肾上腺皮质醇分泌增加，单核白细胞中的糖皮质激素受体下调。糖皮质激素受体下调也可能与淋巴细胞和单核细胞的表型或功能改变（或两者皆有）有关。这种可能性应该得到证实，因为它可以解释围产期奶牛疾病易感性增加的现象。
