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甾体代谢组学与多胎妊娠。

Steroid metabolome and multiple pregnancy.

出版信息

Ceska Gynekol. 2022;87(3):217-223. doi: 10.48095/cccg2022217.

Abstract

Steroid biosynthesis occurs in adrenal, gonadal, brain, liver, and placental tissues. Depending on the location of their activity, steroids can be divided into two groups - intracellular and extracellular. Intracellular ones act as transcription factors, suppressing or activating gene expression - they have a so-called genomic effect and therefore their onset of action is slow. Steroids acting extracellularly (non-genome effect) bind to neurotransmitter receptors located on the cytoplasmic cell membrane and thus affect the permeability of the ion channels, the effect of which is much faster, and we refer to them as neuroactive steroids or neurosteroids. While neuroactive steroids can be produced in different tissues of the body, or can be administered externally, neurosteroids are synthetized in cells of the nervous system. Some neuroactive steroids whose levels are extremely elevated in pregnancy (progesterone and its metabolites) are crucial in stabilizing pregnancy and changes in their concentration may influence the onset of parturition. Steroidogenic disorders may be involved in a number of pregnancy pathologies such as premature birth, pre-eclampsia, intrahepatic cholestasis in pregnancy, etc. Our research in collaboration with the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague also focuses on the investigation of multiple pregnancies in terms of biosynthesis, transport, and the effects of steroids. Studies available in the literature so far have not provided a comprehensive analysis of the steroidome in children and mothers in multiple pregnancies. The aim of our research is therefore to clarify the relationships between fetuses and mothers and between fetuses from the point of view of steroid synthesis and transport as well as the physiology and pathophysiology of human pregnancy and childbirth.

摘要

甾体生物合成发生在肾上腺、性腺、脑、肝和胎盘组织中。根据其活性部位的不同,甾体可以分为两类 - 胞内和胞外。胞内甾体作为转录因子,抑制或激活基因表达 - 它们具有所谓的基因组效应,因此其作用起效较慢。而胞外甾体(非基因组效应)与位于细胞质细胞膜上的神经递质受体结合,从而影响离子通道的通透性,其作用起效更快,我们称之为神经活性甾体或神经甾体。虽然神经活性甾体可以在体内的不同组织中产生,或者可以外部给药,但神经甾体是在神经系统的细胞中合成的。一些在妊娠期间水平极高的神经活性甾体(孕酮及其代谢物)对于稳定妊娠至关重要,其浓度的变化可能会影响分娩的开始。甾体生物合成障碍可能涉及许多妊娠病理,如早产、子痫前期、妊娠肝内胆汁淤积症等。我们与布拉格内分泌研究所的类固醇和蛋白因子部合作进行的研究还侧重于从生物合成、运输以及甾体的作用等方面研究多胎妊娠。迄今为止,文献中的研究尚未对多胎妊娠中的儿童和母亲的甾体组进行全面分析。因此,我们的研究旨在从甾体合成和运输以及人类妊娠和分娩的生理学和病理生理学的角度阐明胎儿和母亲以及多胎妊娠中胎儿之间的关系。

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