HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta

Alison Dickson, Eylan Yutuc, Catherine A. Thornton, James E. Dunford, Udo Oppermann, Yuqin Wang, William J. Griffiths*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number220313
Number of pages19
JournalOpen Biology
Issue number5
Publication statusPublished - 3 May 2023


  • Bile acid
  • HSD3B1
  • Mass spectrometry
  • Oxysterol
  • Placenta
  • Pregnancy


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