Sun K, Yang K, Challis J R
Department of Physiology, University of Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 1997 Jan;82(1):300-5. doi: 10.1210/jcem.82.1.3681.
Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) are present in mammals. 11 beta HSD1 interconverts biologically active cortisol and inactive cortisone, whereas 11 beta HSD2 only converts cortisol to cortisone. Placental 11 beta HSD has been proposed to protect the fetus from high level of maternal glucocorticoids. Although bidirectional activity of 11 beta HSD has been demonstrated in homogenized human placental tissues, the tissue and cellular distribution of 11 beta HSD1 has not been resolved. In this study, the cellular localization of 11 beta HSD1 protein and levels of its messenger ribonucleic acid (mRNA) in human placenta and fetal membranes were determined by immunohistochemistry and Northern blot analysis, respectively. We found that 11 beta HSD1 immunoreactivity was present in the placental extravillous intermediate trophoblasts, chorion trophoblasts, amnion epithelial cells, and stromal cells of the decidua vera. Positive staining was also observed in the endothelium of the blood vessels in both placental villous tissue and umbilical cord. However, in contrast to previous reports of immunoreactive 11 beta HSD2 localization, 11 beta HSD1 immunoreactivity was undetectable in placental syncytiotrophoblast. Using a human 11 beta HSD1 complementary DNA as probe, a 1.5-kilobase mRNA transcript was detected in the chorion, amnion, and placental tissue, with the greatest amount in the chorion. In contrast, the 1.9-kilobase mRNA of 11 beta HSD2 was observed only in the placenta, not in the chorion and amnion. The process of labor had no significant effect on levels of 11 beta HSD1 or 11 beta HSD2 mRNA in the chorion or placenta. We conclude that there is a striking difference in the tissue localization of 11 beta HSD1 and 11 beta HSD2 expression in the late gestation human placenta and fetal membranes, which may discretely determine the accessibility of bioactive glucocorticoid to specific cell types.
哺乳动物体内存在两种11β-羟基类固醇脱氢酶(11βHSD)同工型。11βHSD1可使具有生物活性的皮质醇与无活性的可的松相互转化,而11βHSD2仅能将皮质醇转化为可的松。胎盘11βHSD被认为可保护胎儿免受母体高水平糖皮质激素的影响。尽管在人胎盘组织匀浆中已证实11βHSD具有双向活性,但11βHSD1的组织和细胞分布尚未明确。在本研究中,分别通过免疫组织化学和Northern印迹分析确定了11βHSD1蛋白在人胎盘和胎膜中的细胞定位及其信使核糖核酸(mRNA)水平。我们发现,11βHSD1免疫反应性存在于胎盘绒毛外中间滋养层细胞、绒毛膜滋养层细胞、羊膜上皮细胞和真蜕膜基质细胞中。在胎盘绒毛组织和脐带的血管内皮中也观察到阳性染色。然而,与先前关于免疫反应性11βHSD2定位的报道不同,在胎盘合体滋养层中未检测到11βHSD1免疫反应性。以人11βHSD1互补DNA为探针,在绒毛膜、羊膜和胎盘组织中检测到一条1.5千碱基的mRNA转录本,其中绒毛膜中的含量最高。相比之下,11βHSD2的1.9千碱基mRNA仅在胎盘中观察到,在绒毛膜和羊膜中未观察到。分娩过程对绒毛膜或胎盘中11βHSD1或11βHSD2 mRNA水平无显著影响。我们得出结论,在妊娠晚期人胎盘和胎膜中,11βHSD1和11βHSD2表达的组织定位存在显著差异,这可能分别决定了生物活性糖皮质激素对特定细胞类型的可及性。