Abstract：
:Studies were carried out to elucidate the mechanism whereby thyroid hormone (T3) induces NADPH:cytochrome P450 oxidoreductase (P450R) mRNA in rat liver in vivo. Northern blot analysis revealed that T3 treatment increases unspliced liver nuclear P450R RNA 4-fold within 8 h and that this induction precedes the induction of mature, cytoplasmic P450R RNA. Unspliced nuclear P450R RNA was suppressed below basal levels 24 h after T3 treatment, despite the continued presence of elevated circulating T3 levels. To determine whether the T3-stimulated increase in nuclear P450R RNA reflects an increase in P450R transcription initiation, nuclear run-on transcription assays were carried out. T3 induced a 6- to 8-fold increase in P450R transcription rate within 12 h, sufficient to account for the observed increase in nuclear P450R precursor RNA, followed by a decrease back to basal transcription levels at 24 h, consistent with the nuclear RNA profile. Similar transcriptional increases were observed in nuclear run-on transcription studies using hybridization probes corresponding to nine different fragments of the P450R gene, spanning exon 2 to exon 16. Thus, P450R transcription initiation, not transcription elongation, is the T3-regulated event. Similar results were obtained during short (5 min) compared with long (45 min) nuclear run-on transcription assays, suggesting that changes in nuclear RNA processing or regulated degradation do not contribute to the overall RNA induction. This finding was confirmed by the ability of the RNA polymerase inhibitor actinomycin D, administered in vivo, to block T3 induction of P450R transcriptional activity. We conclude that P450R transcription, rather than nuclear RNA processing or mRNA stabilization, is the primary mechanism whereby T3 induces hepatic P450R mRNA.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Li HC,Liu D,Waxman DJdoi
10.1124/mol.59.5.987keywords:
subject
Has Abstractpub_date
2001-05-01 00:00:00pages
987-95issue
5eissn
0026-895Xissn
1521-0111journal_volume
59pub_type
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
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