Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis.
Type 2 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid and activity in human placenta and fetal membranes: its relationship to birth weight and putative role in fetal adrenal steroidogenesis.
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DOI：
10.1210/jcem.80.3.7883847
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发表时间：
1995-03
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影响因子：
--
通讯作者：
P. Stewart;F. Rogerson;J. Mason
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文献类型：
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作者：
P. Stewart;F. Rogerson;J. Mason
11 β -羟基类固醇脱氢酶（11 β - HSD）的两种异构体已被描述为催化皮质醇(F)向可的松(E)的相互转化。11 β - HSD活性先前已被报道在胎盘和胎膜中，其作用可能是保护发育中的胎儿免受糖皮质激素过量的影响。此外，在大鼠中，胎盘11 β HSD活性与后代高血压的后续发展之间存在关联。我们鉴定了11 β HSD在人胎膜和足月解剖胎盘组织中的同工型，并研究了胎盘11 β HSD活性与胎儿和胎盘体重的关系。在0.1 μ mol/L F和NAD（指示2型异构体活性）存在下的11项β - HSD活性研究显示，无血管解剖的滋养细胞具有高水平的活性（561 +/- 87 pmol E/h）。毫克的蛋白质;N = 4) >未剥离胎盘>从滋养层剥离的子叶血管>胎盘和反射羊膜。相比之下，在2.5 μ mol/L F和NADP（指示1型异构体活性）存在时，只有蜕膜和绒毛膜表现出显著水平的11 β HSD活性。在双胎妊娠获得的无蜕膜的融合绒毛膜中不存在11 β HSD活性，因此绒毛膜中的11 β HSD活性可能是由于蜕膜污染所致。与这些数据一致的是，在蜕膜中检测到11型β - HSD信使核糖核酸（1.5千碱基），但在其他组织中未检测到，在未剥离的胎盘和滋养细胞中发现高水平的11型β - HSD信使核糖核酸（1.9千碱基）。在27个足月胎盘中，11 β HSD活性在194-448 pmol E/h之间变化。毫克的蛋白质。足月胎盘11 β HSD活性与胎儿体重呈微弱但显著的正相关（r = 0.408; P = 0.034），与胎盘体重无相关性。因此，在男性中，报道的小胎儿和大胎盘易导致成人高血压的关联不能以11 β HSD活性缺陷为基础来解释。然而，胎盘提供了一个巨大的F清除库（1.73-7.95 μ mol/min）。胎盘)，可能是驱动胎儿ACTH分泌的主要因素，因此，胎儿肾上腺甾体生成。
Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) have been described which catalyze the interconversion of cortisol (F) to cortisone (E). 11 beta HSD activity has previously been reported in placenta and fetal membranes, where its role may be to protect the developing fetus from glucocorticoid excess. Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported. We have characterized the isoforms of 11 beta HSD in human fetal membranes and dissected placental tissue at term and investigated the relationship between placental 11 beta HSD activity and fetal and placental weights. 11 beta HSD activity studies in the presence of 0.1 mumol/L F and NAD (indicative of type 2 isoform activity) revealed high levels of activity in trophoblast dissected free of vessels (561 +/- 87 pmol E/h.mg protein; n = 4) > undissected placenta > cotyledenous vessels dissected away from trophoblast > placental and reflected amnion. In contrast, in the presence of 2.5 mumol/L F and NADP (indicative of type 1 isoform activity), only decidua and chorion demonstrated significant levels of 11 beta HSD activity. Type 1 11 beta HSD activity in chorion was probably due to decidual contamination, in that it was absent in decidua-free fused chorion obtained from a twin pregnancy. In keeping with these data, type 1 11 beta HSD messenger ribonucleic acid (1.5 kilobases) was detected in decidua, but in no other tissue, and high levels of type 2 11 beta HSD messenger ribonucleic acid (1.9 kilobases) were found in undissected placenta and trophoblast. In 27 term placentas, 11 beta HSD activity varied from 194-448 pmol E/h.mg protein. There was a weak, but significant, positive correlation between term placental 11 beta HSD activity and fetal weight (r = 0.408; P = 0.034), but no correlation with placental weight. Thus, in man, the reported association of a small fetus and a large placenta predisposing to adult hypertension cannot be explained on the basis of defective 11 beta HSD activity. However, the placenta offers an immense reservoir for F clearance (1.73-7.95 mumol/min.placenta) and may be a principal factor driving fetal ACTH secretion and, hence, fetal adrenal steroidogenesis.