HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
Abstract
Most biologically active oxysterols have a 3β-hydroxy-5-ene function in the ring system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ 5 -C 27 -steroid oxidoreductase Δ 5 -isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group. These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognized 3β-hydroxy-Δ 5 -C 27 -steroid oxidoreductase Δ 5 -isomerase activity of HSD3B1, an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate that HSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women's plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus.
Citation
Dickson , A , Yutuc , E , Thornton , C A , Dunford , J E , Oppermann , U , Wang , Y & Griffiths , W J 2023 , ' HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta ' , Open Biology , vol. 13 , no. 5 , 220313 . https://doi.org/10.1098/rsob.220313
Publication
Open Biology
Status
Peer reviewed
ISSN
2046-2441Type
Journal article
Description
Funding Information: This work was supported by funding from the Biological Sciences Research Council (BBSRC, grant nos. BB/I001735/1, BB/N015932/1 and BB/S019588/1 to W.J.G., BB/L001942/1 to Y.W.), and the European Union, through European Structural Funds (ESF), as part of the Welsh Government funded Academic Expertise for Business project (to W.J.G. and Y.W.). A.D. was supported via a KESS2 award with Markes International from the Welsh Government and European Social Fund. Work at the Oxford laboratory was supported by the LEAN network grant by the Leducq Foundation (U.O.). J.E.D. is supported by NIHR Oxford Biomedical Research Centre, Oxford, UK.Collections
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