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".
|Number of pages||10|
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|Publication status||Published - 2014 Jan|
Bibliographical noteFunding Information:
This study was supported by an intramural grant from the Korea Institute of Science and Technology (KIST) and by the Converging Research Center Program through the Ministry of Education, Science and Technology ( 2012K001502 ).
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Cell Biology