Trummer Olivia, Stern Christina, Reintar Sharmaine, Mayer-Pickel Karoline, Cervar-Zivkovic Mila, Dischinger Ulrich, Kurlbaum Max, Huppertz Berthold, Fluhr Herbert, Obermayer-Pietsch Barbara
Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, 8036 Graz, Austria.
Department of Obstetrics and Gynecology, Division of Obstetrics, Medical University of Graz, 8036 Graz, Austria.
Int J Mol Sci. 2024 Nov 26;25(23):12704. doi: 10.3390/ijms252312704.
Steroid hormone imbalance is associated with the pathogenesis of preeclampsia. However, affected enzymes of steroid metabolism and gene and protein expression in serum and placenta have not been elucidated yet. We aimed to investigate steroid hormone profiles and precursor-to-product ratios in preeclamptic women compared to women with healthy pregnancy (controls) to identify potentially affected steroid hormones and their metabolizing enzymes. Also, we aimed to investigate whether the mRNA expression of these enzymes is different between the study groups and whether levels of serum mRNA expression reflect postnatal placental protein expression. Serum levels of 14 steroid hormones were measured at eight time points throughout pregnancy in nine preeclamptic women and 36 controls. Serum mRNA expression of selected steroid-metabolizing enzymes was assessed, and their protein expression was analyzed in additional nine preeclamptic women. Mean levels of sex steroid and corticosteroid hormones were significantly altered in preeclamptic women. Precursor-to-product ratios of 5α-reductase, aromatase and 11β-hydroxysteroid dehydrogenase 1 were significantly increased, those of steroid 17α-hydroxylase, 17β-hydroxysteroid-dehydrogenase, steroid 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase 2 were significantly decreased. Serum mRNA expression and placenta protein expression were comparable between the groups. Results contribute to understanding the heterogeneity of preeclampsia and can thus promote future research in personalized medicine.
类固醇激素失衡与子痫前期的发病机制有关。然而，类固醇代谢相关酶以及血清和胎盘中基因与蛋白质的表达情况尚未阐明。我们旨在比较子痫前期女性与正常妊娠女性（对照组）的类固醇激素谱及其前体与产物的比例，以确定可能受到影响的类固醇激素及其代谢酶。此外，我们还旨在研究这些酶的mRNA表达在研究组之间是否存在差异，以及血清mRNA表达水平是否反映产后胎盘蛋白质表达情况。在整个孕期的八个时间点，对9名子痫前期女性和36名对照组女性的血清中14种类固醇激素水平进行了测量。评估了选定类固醇代谢酶的血清mRNA表达，并对另外9名子痫前期女性的蛋白质表达进行了分析。子痫前期女性中性类固醇和皮质类固醇激素的平均水平有显著改变。5α-还原酶、芳香化酶和11β-羟基类固醇脱氢酶1的前体与产物比例显著升高，而类固醇17α-羟化酶、17β-羟基类固醇脱氢酶、类固醇11β-羟化酶和11β-羟基类固醇脱氢酶2的比例则显著降低。两组之间血清mRNA表达和胎盘蛋白质表达具有可比性。这些结果有助于理解子痫前期的异质性，从而推动未来个性化医学的研究。
