Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report explores the ability of various steroids to rapidly stimulate Sertoli cell RNA polymerase II activity and to compete with [3H]-androgens for nuclear and cytosol binding sites. Nuclear RNA polymerase II activity was significantly stimulated by a 1 nM concentration of the androgenic compounds testosterone, dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one). R1881 (methyltrienolone) and 5 alpha, 17 beta-diol and also by the potent progestins 6 alpha methylprogesterone and R5020 (17,21-dimethyl-19-nor-4-pregna-3,20-dione). Progesterone, 17 alpha-hydroxyprogesterone, estradiol, androsterone, and 5 alpha-androstan-3 beta, 17 beta-diol were ineffective at 1 nM. Cytosol binding and nuclear accumulation of [3H]-androgen was effectively reduced by 100 fold molar excess of those androgens and progestins which stimulated RNA polymerase II activity. These data suggest that androgens and progestins bind to at least some of the same proteins in the Sertoli cell and may elicit the rapid stimulation of RNA polymerase II activity via a common mechanism. Agarose gel electrophoresis of the nuclear RNA synthesized as a result of exposure to testosterone indicated that is was heterodisperse and in part polyadenylated. Electrophoresis of the poly A+-RNA demonstrated that testosterone administration increased the incorporation of [3H]-UTP into RNA that was larger than 28 S.
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PMID:Specificity and nature of the rapid steroid-stimulated increase in Sertoli cell nuclear RNA polymerase activity. 617 4

In an attempt to distinguish between possible androgen- and progestin-mediated mechanisms in the Sertoli cell, two steroids previously shown to have high affinity for both progesterone and androgen receptors (U13851, 17 alpha-ethynyl-17-hydroxy-7 alpha-methylestr-4-en-3-one and U6817, 17-hydroxy-19-nor-17 alpha-pregn-4-en-3-one) have been compared with respect to a number of parameters with two steroids having high affinity only for progesterone receptors (U49836, 17 beta-methoxyestr-4-en-3-one and U56902, 17-methoxy-17 alpha-pregn-4-3n-20-yn-3-one). U13851 and U6817 were the most potent competitors for cytosol [3H]-R1881 (17-beta-hydroxy-17-methylestra-4,9,11-triene-3-one) binding sites and nuclear accumulation of label. While U49836 and U56902 were considerably less effective as competitors against [3H]-R1881, they were more effective than U13851 and U6817 as competitors against [3H]-progesterone. Only U13851 and R1881 increased Sertoli cell nuclear RNA polymerase II activity. These data substantiate previous suggestions that progestin binding proteins distinct from androgen receptors may exist in Sertoli cells. Moreover, the data also suggest that progestins which stimulate RNA polymerase II activity do so via androgenic mechanisms.
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PMID:Interaction of progestins with Sertoli cell androgen receptors. 682 30

The nuclear accumulation of 3H-androgen had been correlated with the effects of this steroid on nuclear RNA polymerase activity in the Sertoli cell under identical experimental conditions. The synthetic androgen methyltrienolone (R1881) was chosen to avoid ambiguities caused by metabolism of the radioligand. Nuclear accumulation of specifically bound 3H-R1881 was apparent after 5 min and preceded RNA polymerase II activation. RNA polymerase II activity was significantly increased by 10 min after administration of R1881, and the response was maximal at 15 min. Although nuclear binding of 3H-R1881 continued to increase over this interval, the enzyme activity declined to basal levels by 20 min. Saturation of nuclear binding sites required concentrations of R1881 that were approximately one order of magnitude higher than those required for maximal polymerase II activation at 15 min. The results indicate that occupancy of only a small fraction of the specific nuclear binding sites by androgen is required to elicit maximal elevation of RNA polymerase II activity in cultured Sertoli cells.
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PMID:Temporal and quantitative correlations between nuclear androgen binding and stimulation of rna polymerase II activity in Sertoli cells. 697 48

The androgen receptor (AR) plays a key role as a transcriptional factor in prostate development and carcinogenesis. Identification of androgen-regulated genes is essential to elucidate the AR pathophysiology in prostate cancer. Here, we identified androgen target genes that are directly regulated by AR in LNCaP cells, by combining chromatin immunoprecipitation (ChIP) with tiling microarrays (ChIP-chip). ChIP-enriched or control DNAs from the cells treated with R1881 were hybridized with the ENCODE array, in which a set of regions representing approximately 1% of the whole genome. We chose 10 bona fide AR-binding sites (ARBSs) (P<1e-5) and validated their significant AR recruitment ligand dependently. Eight upregulated genes by R1881 were identified in the vicinity of the ARBSs. Among the upregulated genes, we focused on UGT1A and CDH2 as AR target genes, because the ARBSs close to these genes (in UGT1A distal promoter and CDH2 intron 1) were most significantly associated with acetylated histone H3/H4, RNA polymerase II and p160 family co-activators. Luciferase reporter constructs including those two ARBSs exhibited ligand-dependent transcriptional regulator/enhancer activities. The present study would be powerful to extend our knowledge of the diversity of androgen genetic network and steroid action in prostate cancer cells.
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PMID:Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis. 1729 73