Thompson A, Han V K M, Yang K
Department of Obstetrics and Gynaecology, CIHR Group in Fetal and Neonatal Health and Development, Child Health Research Institute, and Lawson Health Research Institute, University of Western Ontario, London, Canada N6A 4V2.
Biol Reprod. 2002 Dec;67(6):1708-18. doi: 10.1095/biolreprod.102.005488.
To gain insight into the role of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes and actions of glucocorticoids in the murine placenta and uterus, the expression pattern of the mRNA for 11beta-HSD1 and 11beta-HSD2 and the glucocorticoid receptor (GR) protein were determined from Embryonic Day 12.5 (E12.5, term = E19) to E18.5 by in situ hybridization and immunohistochemistry, respectively. Consistent with its putative role in regulating the transplacental passage of maternal glucocorticoid to the fetus, 11beta-HSD2 mRNA was highly expressed in the labyrinthine zone (the major site of maternal/fetal exchange) at E12.5, and its level decreased dramatically at E16.5, when it became barely detectable. Remarkably, the silencing of 11beta-HSD2 gene expression coincided with the onset of 11beta-HSD1 gene expression in the labyrinth at E16.5 when moderate levels of 11beta-HSD1 mRNA were detected and maintained to E18.5. By contrast, neither 11beta-HSD1 mRNA nor 11beta-HSD2 mRNA were detected in any cell types within the basal zone from E12.5 to E18.5. Moreover, the expression of 11beta-HSD1 and 11beta-HSD2 in the decidua exhibited a high degree of cell specificity in that the mRNA for both 11beta-HSD1 and 11beta-HSD2 was detected in the decidua-stroma but not in the compact decidua. A distinct pattern was also observed within the endometrium where the mRNA for 11beta-HSD1 was expressed in the epithelium, whereas that for 11beta-HSD2 was confined strictly to the stroma. By comparison, the expression of GR in the placenta and uterus was ubiquitous and unremarkable throughout late pregnancy. In conclusion, the present study demonstrates for the first time remarkable spatial and temporal patterns of expression of 11beta-HSD1 and 11beta-HSD2 and GR in the murine placenta and uterus and highlights the intricate control of not only transplacental passage of maternal glucocorticoid to the fetus but also local glucocorticoid action during late pregnancy.
为深入了解11β-羟类固醇脱氢酶（11β-HSD）的作用以及糖皮质激素在小鼠胎盘和子宫中的作用，分别通过原位杂交和免疫组织化学方法，测定了从胚胎第12.5天（E12.5，足月为E19）至E18.5期间11β-HSD1和11β-HSD2的mRNA表达模式以及糖皮质激素受体（GR）蛋白的表达情况。与11β-HSD2在调节母体糖皮质激素经胎盘传递给胎儿方面的假定作用一致，E12.5时11β-HSD2 mRNA在迷路区（母体/胎儿交换的主要部位）高度表达，而在E16.5时其水平急剧下降，此时几乎检测不到。值得注意的是，在E16.5迷路区11β-HSD2基因表达沉默的同时，检测到中等水平的11β-HSD1 mRNA并持续至E18.5，11β-HSD1基因开始表达。相比之下，从E12.5至E18.5，在基底层的任何细胞类型中均未检测到11β-HSD1 mRNA和11β-HSD2 mRNA。此外，11β-HSD1和11β-HSD2在蜕膜中的表达表现出高度的细胞特异性，即11β-HSD1和11β-HSD2的mRNA在蜕膜基质中被检测到，但在致密蜕膜中未被检测到。在内膜中也观察到一种独特的模式，其中11β-HSD1的mRNA在上皮中表达，而11β-HSD2的mRNA则严格局限于基质。相比之下，在整个妊娠后期，GR在胎盘和子宫中的表达普遍且无明显变化。总之，本研究首次证明了11β-HSD1、11β-HSD2和GR在小鼠胎盘和子宫中表达的显著时空模式，并突出了不仅母体糖皮质激素经胎盘传递给胎儿，而且在妊娠后期局部糖皮质激素作用的复杂调控。
