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HSD3B1 is an Oxysterol 3β-Hydroxysteroid Dehydrogenase in Human Placenta
William Griffiths 
,
Yuqin Wang ,
Eylan Yutuc ,
Cathy Thornton ,
Alison Dickson,
James E Dunford,
Udo Oppermann
,
Yuqin Wang ,
Eylan Yutuc ,
Cathy Thornton ,
Alison Dickson,
James E Dunford,
Udo Oppermann
Open Biology
Swansea University Authors:
William Griffiths , Yuqin Wang , Eylan Yutuc , Cathy Thornton , Alison Dickson
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DOI (Published version): 10.1098/rsob.220313
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 ubiqui...
| Published in: | Open Biology |
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| Published: |
Royal Society
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa62997 |
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| 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-Δ5-C27-steroid oxidoreductase Δ5-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 unrecognised 3β-hydroxy-Δ5-C27-steroid oxidoreductase Δ5-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. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
BBSRC, European Union through European Structural Funds (ESF) as part of the Welsh Government funded Academic Expertise for Business project, KESS2 award from the Welsh Government and European Social Fund. Work at Oxford was supported by the LEAN network grant by the Leducq Foundation (UO). |