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HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
Open Biology, Volume: 13, Issue: 5
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Most biologically active oxysterols have a 3β-hydroxy-5-ene function in thering 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 ubiquit...
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The Royal Society
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Most biologically active oxysterols have a 3β-hydroxy-5-ene function in thering 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-Δ5-C27-steroid oxidoreduc-taseΔ5-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-Δ5-C27-steroid oxidoreductaseΔ5-isomerase activity of HSD3B1,an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate thatHSD3B1 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.
placenta, mass spectrometry, bile acid, pregnancy, HSD3B1, oxysterol
Faculty of Medicine, Health and Life Sciences