Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures

Ju Yeon Moon, Myeong Hee Moon, Ki Tae Kim, Dae Hoon Jeong, Young Nam Kim, Bong Chul Chung, Man Ho Choi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Although preeclampsia has been suggested potential risk factors including placental and systemic inflammation, oxidative stress, and abnormal steroid metabolism during pregnancy, the pathogenesis of preeclampsia has not fully been elucidated, particularly in steroid metabolism. The association between various cytochrome P450 (CYP)-mediated steroid metabolic markers and preeclampsia risk was therefore investigated. The serum levels of 54 CYP-mediated regioselective hydroxysteroids and their substrates were quantitatively evaluated from both pregnant women with preeclampsia (n = 30; age, 30.8 ± 4.5 years) and normotensive controls (n = 30; age, 31.0 ± 3.5 years), who were similar with respect to maternal age, gestational age, and body mass index. The levels of 6ß-, 7a-, and 11ß-hydroxymetabolites of androgens and corticoids were significantly increased in women with preeclampsia. In addition, the levels of oxysterols, including 7a-, 7ß-, 4ß-, 20a-, 24S-, and 27-hydroxycholesterol, were markedly higher, while the levels of 16a-OH-DHEA, 16a-OH-androstenedione, and cholesterol were significantly decreased in patients. The 6ß-hydroxylation of androgens and corticoids by CYP3A4 (P < 0.01), the activation of 20,22-desmolase (a cholesterol side-chain cleavage enzyme) by CYP11A1 (P < 0.00001), and the multi-hydroxylation of cholesterol at C-4ß, C-7a, C-7ß, C-24S, C-27, and C-20a (P < 0.0001) by catalytic or enzymatic reaction (e.g. CYP3A4, CYP7A1, CYP27A1, and CYP46A1) were differed between preeclamptic women and control subjects. In particular, an increased oxysterols (induction > 2.0-fold) were positively correlated with the conditions of preeclampsia. Our metabolic profiling suggests the CYP-mediated alterations in steroid metabolism and hydroxylation in pregnancy-induced hypertension. These multiple markers could serve as background information for improved clinical diagnosis and management during pregnancy. This article is part of a Special Issue entitled "Pregnancy and Steroids".

Original languageEnglish
Pages (from-to)182-191
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume139
DOIs
Publication statusPublished - 2014 Jan 1

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Pre-Eclampsia
Cytochrome P-450 Enzyme System
Steroids
Metabolism
Hydroxylation
Androgens
Adrenal Cortex Hormones
Pregnancy
Hydroxysteroids
Cytochrome P-450 CYP3A
Oxidative stress
Dehydroepiandrosterone
Androstenedione
Pregnancy Induced Hypertension
Maternal Age
Gestational Age
Cholesterol
Association reactions
Pregnant Women
Oxidative Stress

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Moon, Ju Yeon ; Moon, Myeong Hee ; Kim, Ki Tae ; Jeong, Dae Hoon ; Kim, Young Nam ; Chung, Bong Chul ; Choi, Man Ho. / Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures. In: Journal of Steroid Biochemistry and Molecular Biology. 2014 ; Vol. 139. pp. 182-191.
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Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures. / Moon, Ju Yeon; Moon, Myeong Hee; Kim, Ki Tae; Jeong, Dae Hoon; Kim, Young Nam; Chung, Bong Chul; Choi, Man Ho.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 139, 01.01.2014, p. 182-191.

Research output: Contribution to journalArticle

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AU - Moon, Ju Yeon

AU - Moon, Myeong Hee

AU - Kim, Ki Tae

AU - Jeong, Dae Hoon

AU - Kim, Young Nam

AU - Chung, Bong Chul

AU - Choi, Man Ho

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