HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta. Issue 5 (3rd May 2023)

• Record Type: Journal Article
• Authors: Dickson, Alison; Yutuc, Eylan; Thornton, Catherine A.; Dunford, James E.; Oppermann, Udo; Wang, Yuqin; Griffiths, William J.
• Is Part Of: Open biology. Volume 13:Issue 5(2023)
• Publication Date: 2023-05-03
• Subjects: HSD3B1 -- oxysterol -- placenta -- mass spectrometry -- bile acid -- pregnancy; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.220313
• Languages: English
• ISSNs: 2046-2441

Abstract

Abstract : 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 -C27 -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 -C27 -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.