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17-BETA-HYDROXYSTEROID DEHYDROGENASE VI; HSD17B6

17-BETA-HYDROXYSTEROID DEHYDROGENASE VI; HSD17B6

Alternative titles; symbols3-ALPHA-HYDROXYSTEROID EPIMERASE; HSERETINOL DEHYDROGENASE; RODHOXIDATIVE 3-ALPHA-HYDROXYSTEROID DEHYDROGENASEHGNC Approved Gene Symbo...

Alternative titles; symbols

  • 3-ALPHA-HYDROXYSTEROID EPIMERASE; HSE
  • RETINOL DEHYDROGENASE; RODH
  • OXIDATIVE 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE

HGNC Approved Gene Symbol: HSD17B6

Cytogenetic location: 12q13.3 Genomic coordinates (GRCh38): 12:56,752,448-56,787,789 (from NCBI)

▼ Description
Epimerization reactions alter the stereo conformation and function of steroid hormones. HSD17B6 catalyzes the epimerization of 3-alpha-hydroxysteroids.

▼ Cloning and Expression
By screening a rat liver cDNA library with random hexamers derived from a cDNA for rat 17-beta-hydroxysteroid dehydrogenase-6 (17-beta-Hsd6), Biswas and Russell (1997) obtained a cDNA encoding rat Rodh1. By probing a human prostate cDNA library with the rat Rodh1 cDNA, they isolated a cDNA encoding human RODH. The deduced 317-amino acid human RODH protein is 62% identical to the rat Rodh1 protein, which is 65% identical to rat 17-beta-Hsd6. RODH catalyzes the oxidation of 3-alpha-adiol to dihydrotestosterone with NAD(+) as the preferred cofactor, while 17-beta-Hsd6 converts 3-alpha-adiol to androsterone. Northern blot analysis revealed expression of a 1.6-kb RODH transcript predominantly in liver, with lower amounts in spleen, testis, and prostate; an 0.8-kb transcript was detected in placenta. Biswas and Russell (1997) concluded that 3-alpha-adiol is activated by RODH and is inactivated by 17-beta-Hsd6. They proposed that this mechanism may regulate the steady state level of the 3-alpha-adiol transcriptional effector. RODH, like RDH5 (601617), is thus active against both retinoids and steroids.

By RT-PCR with retinol dehydrogenase-specific primers and screening of a liver cDNA library, Huang and Luu-The (2000) obtained a cDNA encoding 3(alpha-to-beta)-hydroxysteroid epimerase, or HSE. Sequence analysis predicted that HSE is identical in length to the RODH sequence reported by Biswas and Russell (1997) and has 95% amino acid identity. Functional analysis indicated that, in the presence of NAD(+), HSE converts androsterone (ADT) to 5-alpha-dione, as expected, and to epi-ADT. Kinetic analysis suggested that the preferred orientation of HSE is 3(alpha to beta), i.e., transforming ADT to epi-ADT, in vitro and in intact cells. Site-directed mutagenesis showed that the RODH sequence lacks HSE activity. Semiquantitative RT-PCR analysis detected highest expression of HSE in liver, followed by spleen, prostate, adrenal, brain, uterus, mammary gland, and placenta. Huang and Luu-The (2000) concluded that HSE catalyzes both oxidative and reductive reactions in a stereoselective manner. They suggested that the RODH sequence reported by Biswas and Russell (1997) may be based on amplification errors.

▼ Gene Function
Huang and Luu-The (2001) showed that in intact cells HSE transformed 5-alpha-dione into epi-ADT, while 3-beta-hydroxysteroid dehydrogenase (see 109715) expressed this activity only in vitro.

▼ Gene Structure
By PCR and genomic sequence analysis, Huang and Luu-The (2001) determined that the HSE gene contains 5 exons and spans 23 kb. Primer extension analysis identified a transcription start site 179 bp upstream from the ATG codon and no TATA box. Promoter analysis revealed multiple potential transcription factor-binding sites.

▼ Mapping
Using FISH, Huang and Luu-The (2001) mapped the HSD17B6 gene to chromosome 12q13, close to the RDH5 and RODH4 genes.

Tags: 12q13.3