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Genes Cells. 2000 Feb;5(2):111-25.

Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes.

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  • 1Department of Medical Chemistry; Department of Obstetrics and Gynecology, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka 570-8506, Japan.

Abstract

BACKGROUND:

20alpha-Hydroxysteroid dehydrogenase (HSD) is a member of the aldo-keto reductase (AKR) superfamily and catalyses the reaction of progesterone to the inactive form 20alpha-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 20alpha-HSD is thought to be responsible for the decrease in plasma progesterone at term. High homology between human 20alpha-HSD [AKR 1C1] cDNA with other AKRs had caused difficulty in gene isolation and expression analysis. Thus, the metabolism of progesterone in the human reproductive system remained unclear.

RESULTS:

By hybridization with rat 20alpha-HSD [AKR 1C8] cDNA and high-stringency polymerase chain reaction (PCR) with gene-specific primers, we were able to isolate the human 20alpha-HSD, bile acid-binding protein (BABP) [AKR 1C2], prostaglandin F synthase (PGFS) [AKR 1C3], and dihydrodiol dehydrogenase (DD) 4 [AKR 1C4] genes. These genes had similar exon-intron organizations and shared a high homology. The four recombinant enzymes encoded by these genes showed distinct substrate specificity. By reverse transcription-PCR analysis, human 20alpha-HSD, BABP and PGFS mRNAs were expressed ubiquitously, while DD4 mRNA was restricted to the liver. Promoter activities of the 20alpha-HSD, BABP and PGFS genes were high, both in ovarian granulosa cells and hepatocytes. Radiation hybridization analysis revealed that all these genes were located close together in chromosome 10.

CONCLUSION:

The human gene encoding for the progesterone-metabolizing enzyme 20alpha-HSD in the female reproductive system was cloned, and its expression and gene localization were elucidated. BABP, PGFS and DD4 genes, which were highly homologous to the 20alpha-HSD gene, were also cloned, and their structure and function were characterized.

PMID:
10672042
[PubMed - indexed for MEDLINE]

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