Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The rat hippocampus 11-beta-hydroxysteroid dehydrogenase (11-HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues. 2. S1 nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11-HSD and the enzyme originally cloned from the liver. 3. These results suggest that there may be multiple 11-HSD isoforms in the hippocampus with different substrate specificities.
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PMID:The heterogeneity of 11-beta-hydroxysteroid dehydrogenase activities in the rat hippocampus implies a complex regulation of steroid hormone action. 152 68

The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) is thought to confer specificity on the nonselective Type I adrenocorticoid receptor by converting glucocorticoids to receptor-inactive metabolites in mineralocorticoid target tissues. S1 nuclease analyses using a rat liver 11-HSD probe demonstrated tissue-specific expression of the 5' region of the 11-HSD gene in the liver, lung, and kidney not evident in previous studies. Renal tissue contained a unique protected species which mapped to a position within the coding region, consistent with a divergence in liver and kidney protein sequences. Screening of a rat kidney cDNA library resulted in the isolation of several clones (11-HSD1B) noncolinear in their 5' regions with the liver sequence (11-HSD1A). Nucleic acid sequence analysis showed that the divergent clones code for a protein lacking a 26-amino acid NH2-terminal putative membrane-spanning signal peptide. The deletion of the leader sequence from the microsomal 11-HSD1A protein may result in a nuclear localization of the 11-HSD1B isoform. The renal 11-HSD1A and 11-HSD1B species increased coordinately during ontogeny and in parallel with the developmental surge in glucocorticoids. At least three alternate sites of polyadenylation were found to be utilized by the 11-HSD gene. Southern blot analysis showed the presence of a single gene in the rat. This study shows the expression of a kidney-specific 11-HSD isoform which may protect the Type I adrenocorticoid receptor from occupation by glucocorticoids in the nucleus of a mineralocorticoid target cell.
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PMID:Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with a truncated N-terminal domain. A potential mechanism for differential intracellular localization within mineralocorticoid target cells. 173 55

The structural gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta HSD) was isolated from a human EMBL3 genomic library. The gene encompasses approximately 8 kilobases of DNA and is comprised of two large introns and three exons encoding amino acid residues 1-48, 49-103, and 104-373, respectively. The exonic sequence is identical to that of the cDNA that we previously isolated and expressed in COS 1 cells. DNA sequence analysis reveals a putative TATA (TATATAA) motif 26 basepairs up-stream of the beginning of exon I, as determined by S1 nuclease protection analysis. However, primer extension analysis using poly(A)+ RNA isolated from both placenta and corpora lutea indicates that the RNA initiates up-stream of the putative TATA motif, and that an additional 53-basepair exon, which is untranslated, is present 5' to the first coding exon. Southern hybridization analysis of genomic DNA using a single exon probe suggests that there may be more than one copy of the gene in the human genome. In addition, we confirm from Southern analysis of genomic DNA isolated from human x hamster somatic cell hybrids that the gene is located on human chromosome 1. These findings will provide a foundation for the characterization of apparent 3 beta HSD clinical deficiencies when these are due to a mutation in the structural gene.
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PMID:Structural analysis of the gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase. 208 86

The isozymes of the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) gene family are responsible for the formation of the 17 beta-hydroxysteroids delta 5-androstene-3 beta,17 beta-diol, testosterone, 17 beta-estradiol, and dihydrotestosterone from their corresponding 17-ketosteroid precursors, thus playing a pivotal role in the formation of active sex steroids in both steroidogenic and peripheral target tissues. To clone the type II 17 beta-HSD gene, the full-length cDNA type II 17 beta-HSD was used as probe to screen a human leukocyte genomic DNA library. The type II 17 beta-HSD gene contains seven exons and spans > 40 kbp. The type II 17 beta-HSD gene encodes two alternatively spliced mRNAs that give rise to the previously identified type IIA 17 beta-HSD protein of 387 amino acids, as well as to a related 291-amino-acid type IIB 17 beta-HSD protein of unknown function. RNA blot analysis revealed the presence of a major 1.45-kb transcript that is abundant in placenta and endometrium. The mRNA cap site has been localized in a region between 179 and 167 nucleotides upstream of the ATG start codon by RNase protection and S1 nuclease mapping analyses. Cloning of the 17 beta-HSD type II gene provides us with the tools to study its transcriptional expression.
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PMID:The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species. 754 91

Glucocorticoid action in several target tissues is dependent on expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), and in the placenta 11 beta-HSD is thought to regulate transfer of active glucocorticoid to the fetus. This study compared expression of the two recognized 11 beta-HSD enzymes, types 1 and 2, in the rat placenta and decidua on Days 16 and 22 of gestation (term = Day 23). According to S1 nuclease protection analysis, although mRNA for 11 beta-HSD-1 was only just detectable in the labyrinth zone on Day 16, by Day 22 this expression had increased almost 20-fold. There was also an increase (approximately 2-fold) in 11 beta-HSD-1 mRNA in the basal zone between Days 16 and 22. In Day 16 decidua, 11 beta-HSD-1 mRNA was also highly expressed, but insufficient tissue was available for analysis on Day 22. Western blot analysis showed that immunoreactive 11 beta-HSD-1 (molecular mass 34 kDa) was present in those tissues with the highest 11 beta-HSD-1 mRNA expression (Day 16 decidua and Day 22 labyrinth zone). With respect to mRNA for 11 beta-HSD-2, high expression was observed in the decidua and labyrinth zone at Day 16, but in the latter this expression then declined 90% by Day 22. In contrast, expression of mRNA for 11 beta-HSD-2 increased more than 3-fold in the basal zone over the same period. Consistent with coexpression of the two 11 beta-HSD enzymes, both 11-oxoreductase and 11 beta-dehydrogenase bioactivity were clearly evident in all tissues, and each varied with stage of gestation. Specifically, 11 beta-dehydrogenase activity in the basal zone increased from 38 +/- 2% (mean +/- SEM) on Day 16 to 56 +/- 2% on Day 22, while 11-oxoreductase activity fell from 55 +/- 3% to 43 +/- 2% over the same period. In contrast, 11 beta-dehydrogenase activity in the labyrinth zone fell with advancing pregnancy (Day 16: 63 +/- 2%; Day 22: 48 +/- 2%). Both 11-oxoreductase (58 +/- 3%) and 11 beta-dehydrogenase (38 +/- 4%) activities were also evident in decidua at Day 16. In conclusion, this study shows that expression of 11 beta-HSD-1 and -2 is zone-specific in the placenta and maternal decidua. Moreover, opposite changes in the expression of the two enzymes occur in the basal and labyrinth zones of the placenta over the last days of pregnancy, indicative of distinct regulatory mechanisms and functional significance for the enzymes in the two placental zones.
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PMID:Zonal distribution of 11 beta-hydroxysteroid dehydrogenase types 1 and 2 messenger ribonucleic acid expression in the rat placenta and decidua during late pregnancy. 890 13