Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies.
Pairs of forward and reverse primers and TaqMan probes specific to each human nuclear receptor were prepared. Analysis of the mRNA expression level of each target of 43 nuclear receptors in total RNA from single and pooled specimens of various human organs (liver, kidney, adrenal gland, lung, heart, brain, cerebellum, skeletal muscle, spleen, thymus, thyroid gland, prostate, testis, uterus, placenta, bone marrow, trachea, and salivary gland) was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The mRNA expression of 33 nuclear receptors (NR1A1, 1A2, 1B1, 1B2, 1B3, 1C1, 1C2, 1C3, 1D1, 1D2, 1F1, 1F2, 1F3, 1H2, 1H3, 1I1, 1I2, 2B1, 2B2, 2B3, 2C1, 2C2, 2F1, 2F2, 3A2, 3B1, 3C1, 3C2, 3C4, 4A1, 4A2, 4A3, and 6A1) was successfully detected in all of the tissues by this method. NR1H4, 2A1, and 3C3 mRNAs were not detectable in the heart, heart, and liver, respectively. NR5A2 mRNA was not detectable in either the brain or cerebellum. NR3A1 mRNA was not detectable in the small intestine, colon, brain, and cerebellum. NR5A1 mRNA was not detectable in the kidney, stomach, small intestine, and colon. NR1I3 mRNA was detected in the liver, kidney, stomach, small intestine, adrenal gland, lung, brain, skeletal muscle, thymus, thyroid gland, prostate, testis, placenta, and trachea. NR2A2 mRNA was detected in the liver, kidney, prostate, testis, uterus, and trachea. NR2E1 mRNA was detected in the adrenal gland, brain, cerebellum, testis, placenta, and bone marrow. NR2E3 mRNA was detected in the adrenal gland, thyroid gland, prostate, testis, uterus, trachea, and salivary gland. This study provides information concerning the tissue distribution of the mRNA expression of 43 human nuclear receptors. The mRNA expression profiles of CYP3A4, CYP3A5 and ABC-transporters are also shown. These results are valuable for establishing a nuclear receptor-mediated screening system for new chemical entities in new drug development.
Nishimura
Masuhiro
M
Department of Drug Metabolism, Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima. nisimums@otsukakj.co.jp
Naito
Shinsaku
S
Yokoi
Tsuyoshi
T
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D009928:Organ Specificity; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D018528:ATP-Binding Cassette Transporters; D000090702:Constitutive Androstane Receptor; D017931:DNA Primers; C000716327:NR1I3 protein, human; D009841:Oligonucleotides; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating