HSD3B1 is an Oxysterol 3β-hydroxysteroid Dehydrogenase in Human Placenta

Overview

Journal Open Biol

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 May 3

PMID 37132223

Authors

Alison Dickson

Eylan Yutuc

Catherine A Thornton

James E Dunford

Udo Oppermann

Yuqin Wang

William J Griffiths

Affiliations

Soon will be listed here.

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-C-steroid oxidoreductase Δ-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-C-steroid oxidoreductase Δ-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.

Citing Articles

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

Dickson A, Yutuc E, Thornton C, Dunford J, Oppermann U, Wang Y Open Biol. 2023; 13(5):220313.

PMID: 37132223 PMC: 10154939. DOI: 10.1098/rsob.220313.

Identification of unusual oxysterols biosynthesised in human pregnancy by charge-tagging and liquid chromatography - mass spectrometry.

Dickson A, Yutuc E, Thornton C, Wang Y, Griffiths W Front Endocrinol (Lausanne). 2022; 13:1031013.

PMID: 36440193 PMC: 9685423. DOI: 10.3389/fendo.2022.1031013.

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