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

Genes Cells. 2000 Feb;5(2):111-25. doi: 10.1046/j.1365-2443.2000.00310.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 20-Hydroxysteroid Dehydrogenases / genetics*
  • 20-Hydroxysteroid Dehydrogenases / metabolism*
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Chromosomes, Human, Pair 10
  • Cloning, Molecular
  • Exons
  • Female
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / genetics*
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Hydroxysteroid Dehydrogenases*
  • Introns
  • Ketone Oxidoreductases / genetics
  • Ketone Oxidoreductases / metabolism
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Placenta / enzymology
  • Polymerase Chain Reaction / methods
  • Pregnancy
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Substrate Specificity
  • Uterus / enzymology


  • Carrier Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • bile acid binding proteins
  • Oxidoreductases
  • Hydroxysteroid Dehydrogenases
  • 20-Hydroxysteroid Dehydrogenases
  • Hydroxyprostaglandin Dehydrogenases
  • prostaglandin-F synthase
  • AKR1C2 protein, human
  • Ketone Oxidoreductases
  • trans-1,2-dihydrobenzene-1,2-diol dehydrogenase

Associated data

  • GENBANK/AB031083
  • GENBANK/AB031084
  • GENBANK/AB031085
  • GENBANK/AB032150
  • GENBANK/AB032151
  • GENBANK/AB032152
  • GENBANK/AB032153
  • GENBANK/AB032154
  • GENBANK/AB032155
  • GENBANK/AB032156
  • GENBANK/AB032157
  • GENBANK/AB032158
  • GENBANK/AB032159
  • GENBANK/AB032160
  • GENBANK/AB032161
  • GENBANK/AB032162
  • GENBANK/AB032163