Division of Toxicology and Neurotoxicology, National Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden; Division of Genetic Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Environ Toxicol Pharmacol. 2002 Mar;11(2):119-26. doi: 10.1016/s1382-6689(01)00111-9.
The ligand activated basic-helix-loop-helix (bHLH)-PAS transcription factor, the aryl hydrocarbon receptor (AHR) protein, heterodimerizes with its partner protein the aryl hydrocarbon receptor nuclear translocator (ARNT). The heterodimer activates transcription via xenobiotic responsive elements to regulate the transcription of a battery of biotransformation genes as well as genes involved in growth, differentiation, and cellular homeostasis. In this study we have investigated the diurnal expression of cytochrome P450 1A1, one of the genes in the AHR target gene battery, in rat pituitary and liver. The mRNA expression patterns of AHR, ARNT, and the periodic gene (PER2) were also analyzed. PER2 belongs to another group of bHLH-PAS transcription factor complexes, which are involved in the control of circadian rhythms. Diurnal variation of cytochrome P450 1A1 (CYP1A1) mRNA expression was observed in the anterior and posterior pituitary and in the liver. The accumulation of CYP1A1 mRNA occurred during different times of the day and exhibited an opposite expression in anterior and posterior pituitary, respectively. A daily upregulation of CYP1A1 and PER2 mRNAs that was in antiphase to the AHR and ARNT mRNAs was seen in the liver. The AHR/ARNT system is considered a defense system against toxic chemicals. The high inducibility of CYP1A1 in the pituitary, shown in an earlier study, as well as the tissue specific expression patterns shown here, suggest that AHR and CYP1A1 may play a physiological role in controlling neuroendocrine functions.
配体激活的碱性螺旋-环-螺旋 (bHLH)-PAS 转录因子,芳香烃受体 (AHR) 蛋白,与它的伴侣蛋白芳香烃受体核转位蛋白 (ARNT) 形成异二聚体。异二聚体通过外源性响应元件激活转录,调节生物转化基因以及参与生长、分化和细胞内稳态的基因的转录。在这项研究中,我们研究了芳香烃受体靶基因电池中的基因之一细胞色素 P450 1A1 在大鼠垂体和肝脏中的昼夜表达。还分析了 AHR、ARNT 和周期基因 (PER2) 的 mRNA 表达模式。PER2 属于另一种 bHLH-PAS 转录因子复合物,参与昼夜节律的控制。在垂体前叶和后叶以及肝脏中观察到细胞色素 P450 1A1 (CYP1A1) mRNA 表达的昼夜变化。CYP1A1 mRNA 的积累发生在一天中的不同时间,并且在前叶和后叶中分别表现出相反的表达。在肝脏中观察到 CYP1A1 和 PER2 mRNAs 的昼夜上调,与 AHR 和 ARNT mRNAs 呈反相。AHR/ARNT 系统被认为是对抗有毒化学物质的防御系统。在前一项研究中显示的垂体中 CYP1A1 的高诱导性以及此处显示的组织特异性表达模式表明,AHR 和 CYP1A1 可能在控制神经内分泌功能方面发挥生理作用。