Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam 50463, Republic of Korea.
College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11891. Epub 2021 Feb 4.
Preeclampsia (PE) is a complication of pregnancy and is characterized by hypertension and proteinuria, threatening both the mother and the fetus. However, the etiology of PE has not yet been fully understood. Since the imbalance of steroid hormones is associated with the pathogenesis of PE, investigating steroidogenic mechanisms under various PE conditions is essential to understand the entire spectrum of pregnancy disorders. Therefore, the current study established three PE and models, and compared the levels of steroid hormones and steroidogenic enzymes within them. In cellular PE models induced by hypoxia, N‑nitro‑L‑arginine methyl ester hydrocholride (L‑NAME) and catechol‑o‑methyltransferase inhibitor, the levels of steroid hormones, including pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA) and testosterone tended to decrease during steroidogenesis. Injection of L‑NAME in pregnant rats led to a reduction in the levels of estradiol and P4 through regulation of cholesterol side‑chain cleavage enzyme (CYP11A1) and 3β‑hydroxysteroid dehydrogenase/δ5 4‑isomerase type 1 (HSD3B1), whereas rats treated with COMT‑I exhibited elevated levels of P5 and DHEA by regulation of the CYP11A1 and aromatase cytochrome P450 (CYP19A1) in the placenta and plasma. The reduced uterine perfusion pressure operation decreased CYP11A1 and increased CYP19A1 expression in placental tissues, whereas steroid hormone levels were not altered. In conclusion, the results of the present study suggest that the induction of PE conditions dysregulates the steroid hormones via regulation of steroidogenic enzymes, depending on specific PE symptoms. These findings can contribute to the development of novel diagnostic and therapeutic modalities for PE, by monitoring and supplying appropriate levels of steroid hormones.
子痫前期 (PE) 是一种妊娠并发症，其特征为高血压和蛋白尿，对母亲和胎儿均构成威胁。然而，PE 的病因尚未完全阐明。由于类固醇激素的失衡与 PE 的发病机制有关，因此研究各种 PE 条件下的类固醇生成机制对于了解整个妊娠障碍谱至关重要。因此，本研究建立了三种 PE 模型，并比较了它们之间的类固醇激素和类固醇生成酶的水平。在缺氧诱导的细胞性 PE 模型中，N‑硝基‑L‑精氨酸甲酯盐酸盐 (L‑NAME) 和儿茶酚‑O‑甲基转移酶抑制剂使类固醇激素，包括孕烯醇酮 (P5)、孕酮 (P4)、脱氢表雄酮 (DHEA) 和睾酮的水平在类固醇生成过程中趋于降低。在怀孕大鼠中注射 L‑NAME 通过调节胆固醇侧链裂解酶 (CYP11A1) 和 3β‑羟甾类脱氢酶/δ5 4‑异构酶 1 型 (HSD3B1) 导致雌二醇和 P4 水平降低，而用 COMT‑I 处理的大鼠通过调节胎盘和血浆中的 CYP11A1 和芳香酶细胞色素 P450 (CYP19A1) 使 P5 和 DHEA 水平升高。子宫灌注压降低手术使胎盘组织中的 CYP11A1 减少和 CYP19A1 表达增加，而类固醇激素水平没有改变。综上所述，本研究结果表明，PE 条件的诱导通过调节类固醇生成酶使类固醇激素失调，具体取决于特定的 PE 症状。这些发现有助于开发用于 PE 的新型诊断和治疗方法，通过监测和提供适当水平的类固醇激素。
