Transport and metabolism of thyrotrophin-releasing hormone across the fetal membrane
Transport and metabolism of thyrotrophin-releasing hormone across the fetal membrane
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DOI：
10.1210/jc.82.10.3399
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发表时间：
1997-10-01
影响因子：
5.8
通讯作者：
Fisk, NM
中科院分区：
文献类型：
--
作者：
Bajoria, R;Ryder, TA;Fisk, NM
为了确定TRH通过人胎膜的转移和代谢，通过将I-125标记的TRH（100，000 cpm）或商业TRH加入到从足月和早产胎盘获得的培养人胎膜的体外模型的母体或胎儿隔室中来研究TRH的双向转运和摄取。跨膜转移也进行了研究，在200 μ M的对羟基汞苯磺酸（p-HMSA），二肽酶酶抑制剂的存在下。肌酸和肝素被用作内部标记物。用SephadexG-10凝胶过滤法将TRH的代谢产物与完整分子分离。电子显微镜证实了膜的结构完整性。放射性标记的TRH和商品化的TRH在早产和足月胎盘中的跨膜转移是相当的。当研究从母体到胎儿的转运时，母体TRH浓度从0时的100%迅速下降至8 h时的19.31 +/- 2.26%，同时胎儿浓度从不可检测增加至最大值2.56 +/- 0.38%，胎母比为0.16 +/- 0.01。TRH从胎儿向母体的转移与母体向胎儿的转移相似。母体和胎儿培养基的层析显示TRH被膜代谢成小分子量片段。用p-HMSA处理膜使TRH从母体向胎儿室的转运增加到18.12 ± 0.91（P < 0.001），胎母比为0.35 ± 0.02（P < 0.001）。虽然p-HMSA也能增加TRH从胎儿到母体的跨膜转运，但其水平低于从母体到胎儿的水平（12.26 ± 1.50%; P < 0.05）。这些结果表明，从妊娠24周开始，人胎膜就作为TRH双向转移的酶屏障。
To determine the transfer and metabolism of TRH by human fetal membranes, the bidirectional transport and uptake of TRH was investigated by adding I-125-labeled TRH (100,000 cpm) or commercial TRH either to the maternal or the fetal compartment of an in vitro model of cultured human fetal membranes obtained from term and preterm placenta. Transmembrane transfer was also studied in the presence of 200 mu M p-hydroxy-mercuriphenyl-sulphonic acid (p-HMSA), a dipeptidase enzyme inhibitor. Creatinine and heparin were used as an internal markers. Metabolites of TRH were separated from intact molecules by gel filtration on Sephadex G-10. The structural integrity of the membrane was confirmed by electron microscopy.The transmembrane transfer of radiolabeled and commercial TRH were comparable across both preterm and term placenta. When transport was studied from the maternal to fetal side, the maternal concentration of TRH declined rapidly from 100% at time 0 to 19.31 +/- 2.26% at 8 h with a concomitant increase in the fetal concentration from undetectable to a maximum of 2.56 +/- 0.38% with a fetomaternal ratio of 0.16 +/- 0.01. Transfer of TRH from the fetal to maternal compartment was similar to that of maternal to fetal. Chromatography of maternal and fetal media showed that TRH was metabolized by the membrane into small molecular weight fragments. Treatment of the membrane with p-HMSA increased TRH transport from the maternal to fetal compartment to 18.12 +/- 0.91 (P < 0.001) with an fetomaternal ratio of 0.35 +/- 0.02 (P < 0.001). Although transmembrane transfer of TRH from the fetal to maternal side was also increased by p-HMSA, levels achieved were less than that from maternal to fetal (12.26 +/- 1.50%; P < 0.05). These results suggest that the human fetal membrane acts as an enzymatic barrier to the bidirectional transfer of TRH from 24 weeks gestation.