Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta.
Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta.
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DOI：
10.3389/fphar.2018.01027
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发表时间：
2018
影响因子：
5.6
通讯作者：
Ellinger I
中科院分区：
文献类型：
--
作者：
Chatuphonprasert W;Jarukamjorn K;Ellinger I
类固醇激素孕激素、雌激素、雄激素和糖皮质激素及其前体胆固醇是成功建立和维持妊娠以及胎儿正常发育所必需的。人类胎盘在母体和胎儿循环的界面形成。它参与类固醇的生物合成和代谢以及母体和胎儿室之间的调节交换。本综述概述了人类胎盘处理类固醇化合物的机制。胆固醇从母亲转运到后代涉及脂蛋白受体，如低密度脂蛋白受体 (LDLR) 和 B 型清道夫受体 I 型 (SRB1) 以及 ATP 结合盒 (ABC) 转运蛋白 ABCA1 和 ABCG1。此外，胆固醇也是胎盘孕激素和雌激素合成的前体。激素合成主要由细胞色素 P-450 (CYP) 酶家族的成员进行，包括 CYP11A1 或 CYP19A1 以及羟基类固醇脱氢酶 (HSD)，例如 3β-HSD 和 17β-HSD。胎盘雌激素合成需要从胎儿和母体血清中输送硫酸盐缀合的前体分子。胎盘对这些前体的摄取是由溶质载体 (SLC) 家族成员介导的，包括钠依赖性有机阴离子转运蛋白 (SOAT)、有机阴离子转运蛋白 4 (OAT4) 和有机阴离子转运多肽 2B1 (OATP2B1)。必须严格调节母体-胎儿糖皮质激素的转运，以确保胎儿健康生长和发育。为此，胎盘表达酶 11β-HSD 1 和 2 以及转运蛋白 ABCB1。本文还总结了不同化合物和疾病对相关转运蛋白、受体和代谢酶的表达水平和活性的影响，并得出结论，将生理状态转变为病理生理状态的调节机制几乎没有被探索过。介绍了人胎盘屏障的结构和细胞组成。虽然胎盘合体滋养层中类固醇的产生、代谢和运输已经被探索了几十年，但关于胎盘-胎儿内皮细胞在这些过程中的作用的信息很少。就胎盘结构和功能而言，物种之间存在显着差异。为了进一步破译胎盘类固醇处理的生理途径及其病理改变，必须采用适当的模型系统。
The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus. The human placenta forms at the interface of maternal and fetal circulation. It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment. This review outlines the mechanisms of human placental handling of steroid compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1. Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis. Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD. Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum. Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1). Maternal–fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development. For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1. This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored. The structure and the cellular composition of the human placental barrier are introduced. While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes. With regard to placental structure and function, significant differences exist between species. To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory.
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影响因子：
3.6
作者：
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通讯作者：
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