权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

STUDIES ON REGULATION OF STEROID HORMONE SYNTHESIS AND METABOLISM IN FETO-PLACENTAL UNIT

胎儿胎盘单位类固醇激素合成与代谢调控的研究

基本信息

批准号：
12672258
负责人：
KOBAYASHI Yoshiharu
金额：
$ 1.34万
依托单位：
Kobe Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672258/
关键词：
16-dehydropregnenolone EIA mother-placenta pregnenolone steroid metabolism 17-hydroxylation 16-hydroxylation GC MS エストリオール

项目摘要

We had identified 16-dehydropregnenolone sulfate (16-DHPS) as a novel steroid in serum from neonate. We also revealed that this steroid is synthesized according to the following process : Pregnenolone sulfate (PregS)→16-hydroxy-PregS (16-OH-PregS) →16-DHPS. However, the physiological significance of 16-DHPS is unclear. The aim of this study is to investigate whether this metabolic pathway regulate the known steroid pathway, PregS→17-hydroxy-PregS (17-OH-PregS)→dehydroepiandrosterone sulfate (DHEAS)→16-OH-DHEAS, because these pathways use common substrate, PregS. Firstly, we developed methods for the measurement of these steroids : PregS, 16-OH-PregS, 16-DHPS, 17-OH-PregS, DHEAS and 16-OH-DHEAS by GC/MS. Methods for the measurement of their unconjugated steroids by EIA were also established (Biol. Pharm. Bull. 24,867 (2001). Using these methods, serum concentrations of these steroids were determined in the samples from pregnant women. Key step of the above two pathways is 17-hydroxylation and 16-hydroxylation of Preg(S). 17- and 16-hydroxylase activities were obtained by the ratio of product/substrate concentration that is 17-OH-Preg(S)/Preg(S) ratio and 16-OH-Preg(S)/Preg(S) ratio, respectively. As a result, the 17-hydroxylase activities were decreased according to the course of pregnancy. Inversely, the 16-hydroxylase activities were increased at term compared with those at the first trimester of pregnancy. There were no significant changes of the product/substrate ratios for the other steroids in the above pathway. Present data suggest that 17-hydroxylation of Preg(S) is to be regulated by 16-hydroxylation of Preg(S).

我们在新生儿血清中鉴定出 16-脱氢孕烯醇酮硫酸盐 (16-DHPS) 是一种新型类固醇。我们还揭示了这种类固醇是根据以下过程合成的：硫酸孕烯醇酮（PregS）→16-羟基-PregS（16-OH-PregS）→16-DHPS。然而，16-DHPS 的生理意义尚不清楚。本研究的目的是调查该代谢途径是否调节已知的类固醇途径，PregS→17-羟基-PregS（17-OH-PregS）→硫酸脱氢表雄酮（DHEAS）→16-OH-DHEAS，因为这些途径使用共同的底物PregS。首先，我们开发了通过 GC/MS 测量这些类固醇的方法：PregS、16-OH-PregS、16-DHPS、17-OH-PregS、DHEAS 和 16-OH-DHEAS。还建立了通过EIA测量其未缀合类固醇的方法(Biol.Pharm.Bull.24,867(2001)。利用这些方法，测定了孕妇样品中这些类固醇的血清浓度。上述两条途径的关键步骤是Preg(S)的17-羟基化和16-羟基化。通过比率获得17-和16-羟化酶活性。产物/底物浓度分别为 17-OH-Preg(S)/Preg(S) 比率和 16-OH-Preg(S)/Preg(S) 比率。结果，17-羟化酶活性随着妊娠过程而降低。相反，与妊娠前三个月相比，足月时 16-羟化酶活性有所增加。产品/底物比例没有显着变化上述途径中的其他类固醇。目前的数据表明，Preg(S) 的 17-羟基化是由 Preg(S) 的 16-羟基化调节的。