Complete amino acid sequence of human placental 17β‐hydroxysteroid dehydrogenase deduced from cDNA

Peltoketo, Hellevi; Isomaa, Veli; Mäentausta, O.; Vihko, R.

doi:10.1016/0014-5793(88)80548-9

Cited by 292 publications

(130 citation statements)

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“…Probes for the 17HSDs were prepared from a 376 bp fragment (nucleotides 1-376) of human 17HSD type 1 cDNA 20 and a 380 bp fragment (nucleotides 191-570) of human 17HSD type 2 cDNA. 21 They were cloned into pGEM-4Z plasmids (Promega, Madison, WI), and used as templates for in vitro transcription.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Downregulation of estrogen‐metabolizing 17β‐hydroxysteroid dehydrogenase Type 2 expression correlates inversely with Ki67 proliferation marker in colon‐cancer development

Oduwole

Isomaa

Nokelainen

et al. 2001

Intl Journal of Cancer

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The 17HSDs are a group of isozymes that catalyze the interconversion between high-activity 17␤-hydroxysteroids and low-activity 17-ketosteroids. In the present study, we characterized the expression of 17HSD types 1 and 2 in normal and malignant gastrointestinal tissues and cells. Using the colon as a model for cancer of the gastrointestinal tract, expression of the 17HSD enzymes in cancer development was studied and correlated with proliferation and differentiation markers as assessed by Ki67 and mucin staining, respectively. In normal colon and small intestine, 17HSD type 2 mRNA was expressed in the surface epithelial cells and, to a lesser extent, in the cryptal epithelial cells. In colon-cancer specimens, 17HSD type 2 expression was downregulated both in the tissues and in the cell lines and correlated inversely with the proliferation marker. No expression for the 17HSD type 1 enzyme was observed in normal or cancerous gastrointestinal tract tissues. In line with the expression studies, 17HSD activity measurements with colon cells showed that only the oxidative conversion of E2 to E1 was present, and Northern blot analysis showed the signal only for 17HSD type 2. Localization of the ERs ␣ and ␤, assessed by immunohistochemistry and in situ hybridization, showed the presence of ER␤ in the lamina propria of the colon. Our study shows that 17HSD type 2 expression is associated with the functional integrity of the gastrointestinal tract. The decrease in expression of the type 2 enzyme may increase estrogen influence in colon cancer. © 2002 Wiley-Liss, Inc. Key words: colon carcinoma; estrogen; hydroxysteroid dehydrogenase; cell proliferation; cell differentiationEpidemiologic studies 1,2 and in vitro studies with colon-cancer cell lines 3 suggest the involvement of estrogens in the development and progression of gastrointestinal cancer. [3][4][5] Contrary to this, however, is the indication that HRT is effective at reducing the incidence of colon cancer. 6 The mechanism underlying the sex steroid-mediated effects in normal gastrointestinal physiology and its involvement in neoplastic development and progression, if any, are far from clear.The 17HSDs play pivotal roles in the regulation of the physiologic activities of sex steroid hormones by catalyzing the oxidation or reduction of 17␤-hydroxy-and 17-ketosteroids, respectively. 7,8 17HSDs regulate the concentrations of the active sex steroids that bind to the respective steroid receptors to regulate gene expression in target cells. To date, at least 8 isoforms of the 17HSD enzyme with different substrate and cofactor specificities, tissue distributions and subcellular localizations have been characterized. 8,9 Of these isoforms, 17HSD type 1 and type 2 catalyze opposite reactions of estrogen metabolism. 17HSD type 1 is the predominant enzyme involved in estradiol biosynthesis (E1 to E2), and it is expressed in cells of placental and ovarian origin 10,11 as well as in breast tissue. 12 On the other hand, 17HSD type 2 catalyzes the oxidation of estrogens (E2 to E1...

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Section: In Situ Hybridizationmentioning

confidence: 99%

Downregulation of estrogen‐metabolizing 17β‐hydroxysteroid dehydrogenase Type 2 expression correlates inversely with Ki67 proliferation marker in colon‐cancer development

Oduwole

Isomaa

Nokelainen

et al. 2001

Intl Journal of Cancer

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“…17-HSD gene I1 contained six exons and five introns (Figs 1 and 2) and the exon structure corresponded to the known cDNA species (Peltoketo et al, 1988, Luu The et al, 1989Gast et al, 1989). Both the sequences of the exon/intron junctions and analogous regions in the 17-HSD gene I conformed to the AG/TG rule (Breatnach and Chambon, 1981).…”

Section: Characterization Of the 17-hsd Genesmentioning

confidence: 83%

“…The cDNA encoding human placental 17-HSD has been cloned and sequenced in this laboratory (Peltoketo et al, 1988) and the findings have been independently confirmed (Luu The et al, 1989;Gast et al, 1989 Abbwviations. CRE, Cyclic-AMP-response element; GRE, glucocorticoid-response element; 17-HSD, 17/3-hydroxystcroid dehydrogenase; PCR, polymerase chain reaction; PRE, progesterone-response element; TPA, 12-O-tctradecanoy1phorbol-13-acetate; TRE, AP-1 response element, TPA response element.…”

mentioning

confidence: 85%

“…the human fetal liver genomic DNA Charon 4A library was obtained from American Type Culture Collection. A total of 5 x lo5 plaque-forming units of both libraries were screened by standard methods (Maniatis et al, 1982) using a 32P-labeled EcoRI -SucI-fragment (nucleotides 0 -964) of cDNA encoding human placental 17-HSD (Peltoketo et al, 1988) as a probe. Hybridizations were performed according to standard methods (Maniatis et al, 1982) without formamide at 65°C for 16 -20 h and the filters were washed at 65°C for 30 min each in 2xNaCI/Cit (1 xNaCl/Cit is 150 mM NaCl and 15 mM sodium citrate, pH 7.0) with 0.1 YO SDS, 1 x NaCl/Cit with 0.1% SDS, and 0.5 x NaCl/Cit with 0.1% SDS.…”

Section: Screening Of Genomic Dna Librariesmentioning

confidence: 99%

“…The EcoRI-SucI fragment of 17-HSD cDNA (Peltoketo et al, 1988) was used to screen two human genomic libraries. After screening a total of 5 x lo5 plaque-forming units from both libraries, four positive clones (i17-HSD3, of about 14.5 kbp and 117-HSD5 of about 12 kbp, from the leucocyte library and Al7-HSDI and A1 7-HSD2, both of approximately 13 kbp, from the liver library) were identified, plaque-purified and amplified.…”

Section: Isolation Characterization and Sequencing Of Human 17-hsd Gmentioning

confidence: 99%

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Genomic organization and DNA sequences of human 17β‐hydroxysteroid dehydrogenase genes and flanking regions

Peltoketo

Isomaa

Vihko

1992

European Journal of Biochemistry

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(Received June 18, 1YY2) -EJB 92 0852Genomic 17~-hydroxysteroid-dehydrogenase (1 7-HSD) clones were isolated from a human leucocyte genomic library using cDNA encoding human placental 17-HSD as a probe. The overlapping fragments spanned more than 21 kbp containing the duplications, 6.2 kbp of each, as well as 7 kbp upstream and 1.6 kbp downstream from the duplicated sequences. 17 complete and eight partial A h elements were clustered in this area, covering about 30% of the region, including the borders of the duplications. Each duplication contained a 17-HSD gene and a conserved region of 1.56 kbp with 98% intercopy similarity. The exon structure of the 17-HSD gene I1 corresponded to the known cDNA species, but both genes contained a possible promoter region with TATA, GC and inverse CAAT boxes. The 5' flanking regions contained sequences similar to thc consensus sequences of cis-acting elements, defined as regulators of 17-HSD gene expression. These putative sequences included estrogen and progesterone/glucocorticoid-response elements and a cyclic-AMP regulatory element.Estrogens play a key role in the development, growth and function of hormone-dependent tissues in women. 178-Hydroxysteroid dehydrogenase (17-HSD) is involved in the regulation of estrogen action by catalyzing the reversible reaction between estradiol and the less-active estrone. 17-HSD and/or its isozymes also catalyze interconversions of other neutral and phenolic 17-hydroxysteroids and 17-ketosteroids.

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Characterization of 17B‐hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate

Elo

Akinola

Poutanen

et al. 1996

Intl Journal of Cancer

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In the present study, expressions of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1, 2, and 3, 5alpha-reductase type 2 and human androgen receptor mRNAs were determined in 12 benign prostatic hyperplasia and 17 prostatic carcinoma specimens. 17HSD type 2 was found to be the principle isoenzyme expressed in the prostate. Significantly higher expressions of 17HSD type 2 and 5alpha-reductase type 2 were detected in benign prostatic hyperplasia compared with the carcinoma specimens. Expression of the androgen receptor in the 2 groups was not significantly different. 17HSD type 3 mRNA was not detected in any of the specimens investigated. Only low constructive expression of the 2.3 kb mRNA of 17HSD type 1 was seen. Immunohistochemical analysis indicated that this did not lead to significant enzyme expression, only faint staining for the enzyme protein being detected, mainly in uroepithelial cells. No significant correlation was found between any of the mRNAs analysed, but the data on 5alpha-reductase type 2 mRNA support the presence of an increased proportion of 5alpha-dihydrotesterone in the hyperplastic prostate. In cultured PC-3 prostatic cancer cells and in the transiently transfected human embryonic kidney 293 cells, 17HSD type 2 was found exclusively to convert 5alpha-dihydrotestosterone and testosterone into the less potent 17-keto compounds 5alpha-androstanedione and 4-androstenedione, respectively. We suggest that the 17HSD type 2 isoenzyme plays a part in the metabolic pathway, resulting in the inactivation of testosterone and 5alpha-dihydrotestosterone locally in the prostate. The enzyme expressed in the prostate could, therefore, protect cells from excessive androgen action.

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Complete amino acid sequence of human placental 17β‐hydroxysteroid dehydrogenase deduced from cDNA

Cited by 292 publications

References 21 publications

Downregulation of estrogen‐metabolizing 17β‐hydroxysteroid dehydrogenase Type 2 expression correlates inversely with Ki67 proliferation marker in colon‐cancer development

Downregulation of estrogen‐metabolizing 17β‐hydroxysteroid dehydrogenase Type 2 expression correlates inversely with Ki67 proliferation marker in colon‐cancer development

Genomic organization and DNA sequences of human 17β‐hydroxysteroid dehydrogenase genes and flanking regions

Characterization of 17B‐hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate

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