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

Journal article

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.

Authors: Dickson, A; Yutuc, E; Thornton, CA; Dunford, JE; Oppermann, U

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: The Royal Society
• Journal: Open Biology
• Volume: 13
• Issue: 5
• Pages: 220313
• Article number: 220313
• Publication date: 2023-05-03
• Acceptance date: 2023-03-15
• DOI: 10.1098/rsob.220313
• EISSN: 2046-2441
• ISSN: 2046-2441
• Language: English
• Keywords: oxysterol; bile acid; HSD3B1; mass spectrometry; placenta; pregnancy