Hill M, Parízek A, Klak J, Hampl R, Sulcová J, Havlíková H, Lapcík O, Bicíková M, Fait T, Kancheva R, Cibula D, Pouzar V, Meloun M, Stárka L
Institute of Endocrinology, Národní trída 8, Prague, Czech Republic.
J Steroid Biochem Mol Biol. 2002 Oct;82(2-3):241-50. doi: 10.1016/s0960-0760(02)00188-7.
Five 3beta-hydroxy-5-ene steroids involved in the metabolic route from pregnenolone sulfate to dehydroepiandrosterone and its sulfate, of which three are known allosteric modulators of neurotransmitter receptors, were monitored in the serum of 20 women around parturition. In addition, their levels in maternal and umbilical serum were compared at delivery. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed. In maternal serum, all the steroids except dehydroepiandrosterone sulfate decreased during labor and even first day after delivery, although their changes were less distinct the more distant from pregnenolone sulfate (PregS) in the metabolic pathway. Calculation of product/immediate precursor ratios in maternal serum over all stages around parturition enabled identification of the respective changes in the activities of the relevant enzymes. The ratio of 17-hydroxypregnenolone/pregnenolone did not change significantly, while that of dehydroepiandrosterone/17-hydroxypregnenolone grew, indicating increased C17,20 side chain cleavage on the account of C17-hydroxylation both catalyzed by C17-hydroxylase-C17,20-lyase. As was shown by factor analysis, the changes in the maternal steroids were associated with a single common factor, which strongly correlated with all the steroids except dehydroepiandrosterone sulfate. The lack of change in the pregnenolone sulfate/pregnenolone ratio and a marked increase of the ratio dehydroepiandrosterone sulfate to unconjugated dehydroepiandrosterone indicate a different means of formation of both steroid sulfates. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed.
监测了参与从硫酸孕烯醇酮到脱氢表雄酮及其硫酸盐代谢途径的5种3β-羟基-5-烯类固醇，其中3种是已知的神经递质受体变构调节剂，监测对象为20名临近分娩的女性血清。此外，在分娩时比较了母体血清和脐血血清中它们的水平。基于这些数据，提出了分娩前后关键阶段母体生物体中类固醇生物合成的方案。在母体血清中，除硫酸脱氢表雄酮外，所有类固醇在分娩期间甚至分娩后第一天都有所下降，尽管它们在代谢途径中离硫酸孕烯醇酮（PregS）越远，变化越不明显。计算分娩前后所有阶段母体血清中产物/直接前体比率，能够确定相关酶活性的各自变化。17-羟孕烯醇酮/孕烯醇酮的比率没有显著变化，而脱氢表雄酮/17-羟孕烯醇酮的比率增加，表明由于C17-羟化酶-C17,20-裂解酶催化的C17-羟化作用，C17,20侧链裂解增加。因子分析表明，母体类固醇的变化与一个单一的共同因子相关，该因子与除硫酸脱氢表雄酮外的所有类固醇都高度相关。硫酸孕烯醇酮/孕烯醇酮比率没有变化以及硫酸脱氢表雄酮与未结合的脱氢表雄酮比率显著增加，表明两种类固醇硫酸盐的形成方式不同。基于这些数据，提出了分娩前后关键阶段母体生物体中类固醇生物合成的方案。
