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Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures.
MedLine Citation:
PMID:  23474437     Owner:  NLM     Status:  Publisher    
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 6β-, 7α-, and 11β-hydroxymetabolites of androgens and corticoids were significantly increased in women with preeclampsia. In addition, the levels of oxysterols, including 7α-, 7β-, 4β-, 20α-, 24S-, and 27-hydroxycholesterol, were markedly higher, while the levels of 16α-OH-DHEA, 16α-OH-androstenedione, and cholesterol were significantly decreased in patients. The 6β-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-4β, C-7α, C-7β, C-24S, C-27, and C-20α (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.
Ju-Yeon Moon; Myeong Hee Moon; Ki Tae Kim; Dae Hoon Jeong; Young Nam Kim; Bong Chul Chung; Man Ho Choi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-6
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  -     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ltd.
Future Convergence Research Division, Korea Institute of Science and Technology, Seoul 136-791, Korea; Department of Chemistry, Yonsei University, Seoul 120-749, Korea.
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