Tremblay J, Hardy D B, Pereira L E, Yang K
The Lawson Research Institute, St. Joseph's Health Centre, Department of Obstetrics, University of Western Ontario, London, Ontario, Canada N6A 4V2.
Biol Reprod. 1999 Mar;60(3):541-5. doi: 10.1095/biolreprod60.3.541.
The syncytiotrophoblasts of the human placenta express high levels of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the enzyme responsible for the inactivation of glucocorticoids. It has been proposed that the placental 11beta-HSD2 serves as a barrier to protect the fetus from high levels of maternal cortisol. To examine the hypothesis that nutritional signals regulate the expression of 11beta-HSD2 in placental syncytiotrophoblasts, we investigated the effects of retinoic acids (RAs), the major metabolites of vitamin A, on the expression of 11beta-HSD2 using human choriocarcinoma JEG-3 cells as a model. This trophoblast-like cell line displays a number of functional similarities to the syncytiotrophoblast. Treatment for 24 h with all-trans RA (1-1000 nM) resulted in a dose-dependent increase in 11beta-HSD2 activity with a maximal effect (increase to 3-fold) at 100 nM. The effect of all-trans RA (100 nM) was also time-dependent in that the effect was detectable at 6 h and reached its maximum by 48 h. Similar increases in 11beta-HSD2 activity were observed when the cells were treated with 9-cis RA. Results from semi-quantitative reverse transcription-polymerase chain reaction demonstrated that there was a corresponding increase in 11beta-HSD2 mRNA after RA treatment. Moreover, treatment with actinomycin D (100 ng/ml) abrogated the increase in 11beta-HSD2 mRNA induced by RA, indicating an effect on transcription. In conclusion, the present study has demonstrated for the first time that RA, at physiological concentrations, induces 11beta-HSD2 gene expression and enzyme activity in JEG-3 cells. If this occurs in vivo, the present finding suggests that high expression of 11beta-HSD2 in the human placenta may be maintained, at least in part, by dietary intake of vitamin A.
人类胎盘的合体滋养层细胞表达高水平的2型11β-羟基类固醇脱氢酶（11β-HSD2），该酶负责使糖皮质激素失活。有人提出，胎盘11β-HSD2作为一种屏障，保护胎儿免受母体高水平皮质醇的影响。为了检验营养信号调节胎盘合体滋养层细胞中11β-HSD2表达的假说，我们以人绒毛膜癌JEG-3细胞为模型，研究了维生素A的主要代谢产物视黄酸（RA）对11β-HSD2表达的影响。这种滋养层样细胞系与合体滋养层细胞表现出许多功能相似性。用全反式视黄酸（1-1000 nM）处理24小时导致11β-HSD2活性呈剂量依赖性增加，在100 nM时达到最大效应（增加到3倍）。全反式视黄酸（100 nM）的作用也是时间依赖性的，在6小时时可检测到该作用，并在48小时时达到最大值。当用9-顺式视黄酸处理细胞时，观察到11β-HSD2活性有类似的增加。半定量逆转录-聚合酶链反应结果表明，视黄酸处理后11β-HSD2 mRNA相应增加。此外，用放线菌素D（100 ng/ml）处理可消除视黄酸诱导的11β-HSD2 mRNA增加，表明对视黄酸转录有影响。总之，本研究首次证明，生理浓度的视黄酸可诱导JEG-3细胞中11β-HSD2基因表达和酶活性。如果这在体内发生，本研究结果表明，人胎盘中11β-HSD2的高表达可能至少部分由维生素A的饮食摄入维持。
