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

Dickson, Alison; Yutuc, Eylan; Thornton, Cathy; Dunford, James E.; Oppermann, Udo; Wang, Yuqin; Griffiths, William

doi:10.1098/rsob.220313

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

Alison Dickson, Eylan Yutuc

, Cathy Thornton

, James E. Dunford

, Udo Oppermann, Yuqin Wang

, William Griffiths

Open Biology, Volume: 13, Issue: 5

Swansea University Authors: Alison Dickson, Eylan Yutuc , Cathy Thornton , Yuqin Wang , William Griffiths

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DOI (Published version): 10.1098/rsob.220313

Abstract

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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Published in:	Open Biology
ISSN:	2046-2441
Published:	The Royal Society 2023
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URI:	https://cronfa.swan.ac.uk/Record/cronfa61629
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first_indexed	2022-11-16T09:58:33Z
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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. 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spelling	v2 61629 2022-10-21 HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta 82dc4360769527a5f3a0cd9d85cdff40 Alison Dickson Alison Dickson true false 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2022-10-21 BMS 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. Journal Article Open Biology 13 5 The Royal Society 2046-2441 placenta, mass spectrometry, bile acid, pregnancy, HSD3B1, oxysterol 1 5 2023 2023-05-01 10.1098/rsob.220313 http://dx.doi.org/10.1098/rsob.220313 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University SU Library paid the OA fee (TA Institutional Deal) 2023-11-15T12:41:02.8708421 2022-10-21T09:46:59.5002597 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Alison Dickson 1 Eylan Yutuc 0000-0001-9971-1950 2 Cathy Thornton 0000-0002-5153-573X 3 James E. Dunford 0000-0002-9932-4042 4 Udo Oppermann 5 Yuqin Wang 0000-0002-3063-3066 6 William Griffiths 0000-0002-4129-6616 7 61629__27805__17987f2615a14b3eac84c8f5f4b7fd2f.pdf 61629.pdf 2023-06-12T14:24:36.9565555 Output 3685048 application/pdf Version of Record true 2023 The Authors. Published by the Royal Society under the terms of the Creative Commons AttributionLicense http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the originalauthor and source are credited. true eng http://creativecommons.org/licenses/by/4.0/
title	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
spellingShingle	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta Alison Dickson Eylan Yutuc Cathy Thornton Yuqin Wang William Griffiths
title_short	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
title_full	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
title_fullStr	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
title_full_unstemmed	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
title_sort	HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
author_id_str_mv	82dc4360769527a5f3a0cd9d85cdff40 99332f073ce913a9b7d8b6441b17516d c71a7a4be7361094d046d312202bce0c c92729b58622f9fdf6a0e7d8f4ce5081 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv	82dc4360769527a5f3a0cd9d85cdff40_*_Alison Dickson 99332f073ce913a9b7d8b6441b17516d__Eylan Yutuc c71a7a4be7361094d046d312202bce0c__Cathy Thornton c92729b58622f9fdf6a0e7d8f4ce5081__Yuqin Wang 3316b1d1b524be1831790933eed1c26e_**_William Griffiths
author	Alison Dickson Eylan Yutuc Cathy Thornton Yuqin Wang William Griffiths
author2	Alison Dickson Eylan Yutuc Cathy Thornton James E. Dunford Udo Oppermann Yuqin Wang William Griffiths
format	Journal article
container_title	Open Biology
container_volume	13
container_issue	5
publishDate	2023
institution	Swansea University
issn	2046-2441
doi_str_mv	10.1098/rsob.220313
publisher	The Royal Society
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url	http://dx.doi.org/10.1098/rsob.220313
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description	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.
published_date	2023-05-01T12:41:06Z
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HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta

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