Greger D L, Blum J W
Division of Nutrition and Physiology, Institute of Animal Genetics, Nutrition and Housing, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
J Anim Physiol Anim Nutr (Berl). 2007 Feb;91(1-2):62-7. doi: 10.1111/j.1439-0396.2006.00642.x.
Hepatic nuclear receptors (NR), particularly constitutive androstane receptor (CAR) and pregnane X receptor (PXR), are involved in the coordinated transcriptional control of genes that encode proteins involved in the metabolism and detoxification of xeno- and endobiotics. A broad spectrum of metabolic processes are mediated by NR acting in concert with ligands such as glucocorticoids. This study examined the role of dexamethasone on hepatic mRNA expression of CAR, PXR and several NR target genes. Twenty-eight male calves were allotted to one of four treatment groups in a 2 x 2 arrangement of treatments: feed source (colostrum or milk-based formula) and glucocorticoid administration (twice daily intramuscular dexamethasone). Liver biopsies were obtained at 5 days of age. Real-time reverse transcription polymerase chain reaction was used to quantify mRNA abundances. No effects of feed source on mRNA abundances were observed. For the NR examined, mRNA abundance of both CAR and PXR in dexamethasone-treated calves was lower (p < 0.05) by 39% and 40%, respectively, than in control calves. Abundance of NR target genes exhibited a mixed response. SULT1A1 mRNA abundance was 39% higher (p < 0.05) in dexamethasone-treated calves compared with control calves. mRNA abundance of CYP2C8 tended also to be higher (+44%; p = 0.053) after dexamethasone treatment. No significant treatment effects (p > 0.10) were observed for mRNA abundances of CYP3A4, CYP2E1, SULT2A1, UGT1A1 or cytochrome P450 reductase (CPR). In conclusion, an enhanced glucocorticoid status, induced by pharmacological amounts of dexamethasone, had differential and in part unexpected effects on NR and NR target systems in 5-day-old calves. Part of the unexpected responses may be due the immaturity of NR and NR receptor target systems.
肝细胞核受体（NR），尤其是组成型雄甾烷受体（CAR）和孕烷X受体（PXR），参与对编码参与外源性和内源性生物代谢及解毒相关蛋白质的基因进行协调转录控制。NR与糖皮质激素等配体协同作用，介导了广泛的代谢过程。本研究考察了地塞米松对CAR、PXR及多个NR靶基因肝脏mRNA表达的作用。28头雄性犊牛按2×2处理组合被分配到四个处理组之一：饲料来源（初乳或乳基配方奶）和糖皮质激素给药（每日两次肌肉注射地塞米松）。在犊牛5日龄时采集肝脏活检样本。采用实时逆转录聚合酶链反应定量mRNA丰度。未观察到饲料来源对mRNA丰度有影响。在所检测的NR中，地塞米松处理的犊牛中CAR和PXR的mRNA丰度分别比对照犊牛低39%和40%（p<0.05）。NR靶基因的丰度表现出混合反应。与对照犊牛相比，地塞米松处理的犊牛中SULT1A1的mRNA丰度高39%（p<0.05）。地塞米松处理后，CYP2C8的mRNA丰度也有升高趋势（升高44%；p=0.053）。对于CYP3A4、CYP2E1、SULT2A1、UGT1A1或细胞色素P450还原酶（CPR）的mRNA丰度，未观察到显著的处理效应（p>0.10）。总之，药理剂量的地塞米松诱导的糖皮质激素状态增强，对5日龄犊牛的NR和NR靶系统产生了不同且部分出乎意料的影响。部分出乎意料的反应可能归因于NR和NR受体靶系统的不成熟。
