3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period
3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period
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DOI：
10.1080/09513590500361747
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发表时间：
2005-11-01
影响因子：
2
通讯作者：
Romach, MK
中科院分区：
文献类型：
--
作者：
Evans, SEG;Ross, LE;Romach, MK
别孕烯醇酮（ALLO）和孕烯醇酮（PREG），孕酮（PROG）的3 α-还原代谢物，是γ-氨基丁酸A型受体的强效调节剂，可作为内源性抗焦虑药发挥作用。它们被认为与临床抑郁症的病因或表现有关。在本研究中，我们定量ALLO和PREG，以及PROG，5 α-二氢孕酮（5 α-DHP），5 β-二氢孕酮（5 β-DHP），表别孕烷醇酮和双烯醇酮（PREGNEN），健康妇女在怀孕期间和产后期间的五个时间点的血浆中。通过气相色谱/电子捕获-负化学电离-质谱法进行分析。神经活性类固醇从怀孕10周到36周显着增加，除了5 β-DHP和PREGNEN没有显着变化。PROG是整个妊娠期最丰富的类固醇，其次是5a-DHP和ALLO。代谢物与前体的比例因酶和底物而异：PROG转化为5 α-DHP（由5 α-还原酶催化）的周转率稳定，而PROG转化为5 β-DHP（由5 β-还原酶催化）的转化率在妊娠后期下降。3 α-羟基类固醇氧化还原酶介导的5 α-和5 β-DHP转化为其代谢物ALLO和PREG的周转率在妊娠期间分别升高，但5 α-DHP转化为ALLO的周转率在晚期产前访视时下降。在产后6周，所有类固醇与晚期产前值相比显著减少，其中5a-DHP是最丰富的产后类固醇。这些结果为进一步研究神经活性类固醇在妊娠期和产后精神疾病中的作用提供了依据。
Allopregnanolone (ALLO) and pregnanolone (PREG), the 3 alpha-reduced metabolites of progesterone (PROG), are potent modulators of gamma-aminobutyric acid type A receptors that may function as endogenous anxiolytics. They are purported to be involved in the etiology or expression of clinical depression. In the present study we quantified ALLO and PREG, as well as PROG, 5 alpha-dihydroprogesterone (5 alpha-DHP), 5 beta-dihydroprogesterone (5 beta-DHP), epiallopregnanolone and pregnenolone (PREGNEN), in plasma from healthy women at five time points during pregnancy and the postpartum period. Analysis was by gas chromatography/electron capture-negative chemical ionization-mass spectrometry. Neuroactive steroids increased significantly from 10 to 36 weeks of pregnancy, except for 5 beta-DHP and PREGNEN which did not change significantly. PROG was the most abundant steroid throughout pregnancy, followed by 5a-DHP and ALLO. Metabolite to precursor ratios differed depending on the enzyme and substrate: the turnover of PROG to 5 alpha-DHP (catalyzed by 5 alpha-reductase) was stable while the conversion of PROG to 5 beta-DHP (catalyzed by 5 beta-reductase) decreased later in pregnancy. 3 alpha-Hydroxysteroid oxidoreductase-mediated turnover of 5 alpha- and 5 beta-DHP to their metabolites ALLO and PREG, respectively, rose during pregnancy, but the turnover of 5 alpha-DHP to ALLO dropped at the late prenatal visit. At 6 weeks postpartum all steroids were significantly reduced compared with late prenatal values, with 5a-DHP being the most abundant postpartum steroid. These results provide the basis for further study of neuroactive steroids in psychiatric conditions of pregnancy and the postpartum period.