Arcuri F, Sestini S, Paulesu L, Bracci L, Carducci A, Manzoni F, Cardone C, Cintorino M
Institute of Pathological Anatomy and Histology, University of Siena, Italy.
Mol Cell Endocrinol. 1998 Jun 25;141(1-2):13-20. doi: 10.1016/s0303-7207(98)00103-8.
This study evaluated the levels and the enzymatic characteristics of 11beta-hydroxysteroid dehydrogenase activity (11beta-HSD) of chorionic villi isolated from first trimester human placenta. The results demonstrated a predominant expression of the NAD-dependent dehydrogenase isoform (11beta-HSD2) over the NADP-dependent oxoreductase (11beta-HSD1). Thus, in tissue homogenates exogenous NAD increased the conversion of corticosterone to 11-dehydrocorticosterone of about 14-fold while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11beta-HSD2 in villous tissue while 11beta-HSD1 mRNA levels were undetectable. In addition, immunohistochemical staining localized the 11beta-HSD2 protein to syncytiotrophoblasts and cell columns of the chorionic villi. These results suggest roles for the trophoblast-associated 11beta-HSD2 oxidative activity in modulating the exposure of the embryo to active glucocorticoids in the early gestation and in regulating trophoblasts invasion of the uterine wall.
本研究评估了从孕早期人胎盘分离的绒毛膜绒毛中11β-羟基类固醇脱氢酶活性（11β-HSD）的水平及酶学特性。结果显示，与烟酰胺腺嘌呤二核苷酸磷酸（NADP）依赖性氧化还原酶（11β-HSD1）相比，烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱氢酶同工型（11β-HSD2）表达占主导。因此，在组织匀浆中，外源性NAD使皮质酮向11-脱氢皮质酮的转化增加约14倍，而NADP则无作用。无论使用还原型辅酶I（NADH）还是还原型辅酶II（NADPH），11-脱氢皮质酮均不能转化为皮质酮，表明缺乏还原酶活性。与这些结果一致，逆转录-聚合酶链反应（RT-PCR）分析显示绒毛组织中有11β-HSD2的信使核糖核酸（mRNA），而11β-HSD1的mRNA水平无法检测到。此外，免疫组织化学染色将11β-HSD2蛋白定位于绒毛膜绒毛的合体滋养层细胞和细胞柱。这些结果表明，滋养层相关的11β-HSD2氧化活性在调节胚胎在妊娠早期对活性糖皮质激素的暴露以及调节滋养层对子宫壁的侵袭中发挥作用。
