Characteristic expression of aryl hydrocarbon receptor repressor gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells

Life Sci. 2004 Jan 9;74(8):1039-49. doi: 10.1016/j.lfs.2003.07.022.

Abstract

To investigate the expression of aryl hydrocarbon receptor repressor (AhRR) and related molecules in various tissues and the effects of aromatic hydrocarbons (AHs) on their expression, we developed a reliable technique of quantification of human AhRR as well as aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT) and cytochrome P450 1A1 (CYP1A1) mRNA by real-time TaqMan PCR method. First, we examined the expression of these genes in human adult or fetal tissues. The levels of AhRR expression were extremely high in testis, very high in lung, ovary, spleen and pancreas from adults, whereas those were low in those from fetuses. On the other hand, CYP1A1 expression was extremely high in lung, and AhR and ARNT were ubiquitously expressed in almost all tissues. Second, we compared the expression levels of these genes in mononuclear cells (MNCs) from various sources. Comparison of the basal expression levels of these genes in MNCs demonstrated that MNCs from umbilical cord blood showed higher AhRR or CYP1A1 expression than those from adults. The induction of AhRR or CYP1A1 expression by 3-methylcholanthrene (3-MC) was observed in MNCs from adults but not from umbilical cord blood. Consequently, there existed characteristic differences in the basal levels of AhRR and CYP1A1 expression in MNCs, as well as in their inducibility by 3-MC among MNCs from various types of human bloods. These results will provide basic information for a possible application of AhRR and CYP1A1 measurements to evaluate AH exposure in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinogens / toxicity
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A1 / genetics
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • DNA-Binding Proteins*
  • Dioxins / metabolism
  • Female
  • Fetal Blood / metabolism
  • Gene Expression Regulation / physiology*
  • Humans
  • Infant, Newborn
  • Male
  • Methylcholanthrene / pharmacology
  • Monocytes / metabolism*
  • Organ Specificity
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Aryl Hydrocarbon / biosynthesis
  • Receptors, Aryl Hydrocarbon / genetics*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testis / cytology
  • Testis / drug effects
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • AHRR protein, human
  • ARNT protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinogens
  • DNA, Complementary
  • DNA-Binding Proteins
  • Dioxins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Repressor Proteins
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Methylcholanthrene
  • Cytochrome P-450 CYP1A1