Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3α-hydroxysteroid dehydrogenase

Qin, Kenan; New, Maria I.; Cheng, Kuang-Chuan

doi:10.1016/0960-0760(93)90308-j

Cited by 53 publications

(42 citation statements)

References 19 publications

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“…In the present study, cDNAs encoding 20a-HSD, BABP and DD4 were cloned. Sequences encoding these 20a-HSD, BABP, PGFS and DD4 cDNAs completely matched our exon sequences, as well as those of reported cDNA sequences (Winters et al 1990;Qin et al 1993;Hara et al 1996;SuzukiYamamoto et al 1999) at an amino acid level, and almost identical at a nucleotide level except for a few silent base changes. Then, 20a-HSD, BABP and DD4 were expressed in bacteria and subjected to kinetic analysis in the presence of the cofactor NADPH or NADP to compare substrate speci®city.…”

Section: Substrate Speci®city Of Human 20a-hsd and Three Akrssupporting

confidence: 88%

Close kinship of human 20α‐hydroxysteroid dehydrogenase gene with three aldo‐keto reductase genes

Nishizawa¹,

et al. 2000

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Background: 20a-Hydroxysteroid dehydrogenase (HSD) is a member of the aldo-keto reductase (AKR) superfamily and catalyses the reaction of progesterone to the inactive form 20a-hydroxyprogesterone. Progesterone plays an important role in the maintenance of pregnancy, and, in rodents, plasma progesterone levels decrease abruptly just before parturition. The induction of 20a-HSD is thought to be responsible for the decrease in plasma progesterone at term. High homology between human 20a-HSD [AKR 1C1] cDNA with other AKRs had caused dif®culty in gene isolation and expression analysis. Thus, the metabolism of progesterone in the human reproductive system remained unclear.

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Section: Substrate Speci®city Of Human 20a-hsd and Three Akrssupporting

confidence: 88%

Close kinship of human 20α‐hydroxysteroid dehydrogenase gene with three aldo‐keto reductase genes

Nishizawa¹,

et al. 2000

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“…Three 17 -HSD type 5-specific PCR products were used for complete sequencing. We found differences with respect to the sequence of HAKRb (Qin et al 1993): G instead of T (222nd nt), G instead of A (495th nt), G instead of C (702nd nt), all of which do not alter the amino acid sequence. However, two additionally identified nucleotide substitutions resulted in amino acid changes; A instead of G (223rd nt) changing glutamic acid (75th amino acid) to lysine, and G instead of C (525th nt) changing isoleucine (175th amino acid) to methionine (such as in all other members of the AKR1C family).…”

Section: -Hsd Type 5 Similar To 3 -Hsd (Clone Of Human Aldo-keto Redumentioning

confidence: 93%

“…However, two additionally identified nucleotide substitutions resulted in amino acid changes; A instead of G (223rd nt) changing glutamic acid (75th amino acid) to lysine, and G instead of C (525th nt) changing isoleucine (175th amino acid) to methionine (such as in all other members of the AKR1C family). Our sequencing data show 99·5% homology to the CDS of HAKRb (Qin et al 1993); 99·8% homology was found to the sequence of a recombinant 3 -HSD type 2 with 17 -HSD activity (Lin et al 1997), identified as 17 -HSD type 5 (Penning 1999). Our sequence differed only in the 312th nt with G (such as in the sequence of HAKRb) instead of A, and in the 855th nt with G (such as in the sequences of PGFS and HAKRb) instead of A, both conserving the amino acid sequence of 17 -HSD type 5.…”

Section: -Hsd Type 5 Similar To 3 -Hsd (Clone Of Human Aldo-keto Redumentioning

confidence: 99%

“…Amplifications of three overlapping parts originating from exon 1-5, 4-7 and 6-9 covering nearly the complete CDS (Table 1) were performed with primers according to the homologous sequence of 3 -HSD clone HAKRb (Qin et al 1993) encoding an enzyme differing only in the 75th and 175th amino acid from 17 -HSD type 5. All three expected PCR products of 476, 335 and 469 bp (Table 3) were amplified from cDNAs of all human kidney samples and CV-1 cells as well, the latter missing only the PCR product of the last segment.…”

Section: -Hsd Type 5 Similar To 3 -Hsd (Clone Of Human Aldo-keto Redumentioning

confidence: 99%

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Expression of the progesterone receptor and progesterone- metabolising enzymes in the female and male human kidney

Bumke-Vogt¹,

Bähr²,

Diederich³

et al. 2002

Journal of Endocrinology

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Due to high binding affinity of progesterone to the human mineralocorticoid receptor (hMR), progesterone competes with the natural ligand aldosterone. In order to analyse how homeostasis can be maintained by mineralocorticoid function of aldosterone at the MR, especially in the presence of elevated progesterone concentrations during the luteal phase and pregnancy, we investigated protective mechanisms such as the decrease of free progesterone by additional binding sites and progesterone metabolism in renal cells. As a prerequisite for sequestration of progesterone by binding to the human progesterone receptor (hPR) we demonstrated the existence of hPR expression in female and male kidney cortex and medulla at the level of transcription and translation. We identified hPR RNA by sequencing the RT-PCR product and characterised the receptor by ligand binding and Scatchard plot analysis. The localisation of renal hPR was shown predominantly in individual epithelial cells of distal tubules by immunohistology, and the isoform hPR-B was detected by Western blot analysis. As a precondition for renal progesterone metabolism, we investigated the expression of steroid-metabolising enzymes for conversion of progesterone to metabolites with lower affinity to the hMR. We identified the enzyme 17 -hydroxylase for renal 17 -hydroxylation of progesterone. For 20 -reduction, different hydroxysteroid dehydrogenases (HSDs) such as 20 -HSD, 17 -HSD type 5 (3 -HSD type 2) and 3 -HSD type 3 were found. Further, we detected the expression of 3 -HSD type 2 for 3 -reduction, 5 -reductase (Red) type 1 for 5 -reduction, and 5 -Red for 5 -reduction of progesterone in the human kidney. Therefore metabolism of progesterone and/or binding to hPR could reduce competition with aldosterone at the MR and enable the mineralocorticoid function.

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“…The oxidation of trans-dihydrodiols of ultimate carcinogenic aromatic compounds to their non-carcinogenic catechol metabolites is also mediated by enzymes which belong to the above mentioned groups, and which are often identical to each other, such as cytosolic rat liver 3a-HSDl dihydrodiol dehydrogenase/bile-acid-binding protein (Stolz et al, 1987;Smithgall et al, 1988). Their expression results in a decrease in the mutagenic potential of certain polyaromatic compounds (Glatt et al, 1979;Stolz et al, 1991 ;Pawlowski et al, 1991;Cheng et al, 1991;Klein et al, 1992;Qin et al, 1993). Microsomal-linked carbonyl reductase/quinone reductase activity is associated either with 3u-HSD, 17P-HSD or 11P-HSD (Hara et al, 1987;Sawada et al, 1981;Maser and Bannenberg, 1994) which probably also belong to the short-chain and/or aldoketo reductase branch of dehydrogenases.…”

Section: Discussionmentioning

confidence: 99%

Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

Oppermann

Netter

Maser

1995

European Journal of Biochemistry

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Screening of a mouse liver Agt 11 cDNA library with a rat liver 1lP-hydroxysteroid dehydrogenase cDNA (11P-HSDrlA) and subsequent screening with an isolated mouse probe, resulted in the isolation and structure determination of a mouse cDNA encoding an amino acid sequence which is very similar to human and rat 11P-hydroxysteroid dehydrogenases (78 % and 86 % similar, respectively), and also to other known vertebrate 1 lP-hydroxysteroid dehydrogenase structures. Open-reading-frame analysis and the deduced amino acid sequence predict a protein with a molecular mass of 32.3 kDa which beIongs to the superfamily of the short-chain dehydrogenase proteins. The amino acid sequence contains two potential glycosylation sites. These data are in agreement with information on the glycoprotein character of the native enzyme. This kind of post-translational modification seems to be a determining factor concerning the equilibrium of the catalyzed llP-dehydrogenation/ll -ox0 reduction step [Obeid,

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Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3α-hydroxysteroid dehydrogenase

Cited by 53 publications

References 19 publications

Close kinship of human 20α‐hydroxysteroid dehydrogenase gene with three aldo‐keto reductase genes

Close kinship of human 20α‐hydroxysteroid dehydrogenase gene with three aldo‐keto reductase genes

Expression of the progesterone receptor and progesterone- metabolising enzymes in the female and male human kidney

Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

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