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Retinoic Acid Stimulates the Expression of 11ß-Hydroxysteroid Dehydrogenase Type 2 in Human Choriocarcinoma JEG-3 Cells¹

^a The Lawson Research Institute, St. Joseph's Health Centre, Departments of Obstetrics and Gynecology and Physiology, University of Western Ontario, London, Ontario, Canada N6A 4V2

The syncytiotrophoblasts of the human placenta express high levels of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), the enzyme responsible for the inactivation of glucocorticoids. It has been proposed that the placental 11ß-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 11ß-HSD2 in placental syncytiotrophoblasts, we investigated the effects of retinoic acids (RAs), the major metabolites of vitamin A, on the expression of 11ß-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 11ß-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 11ß-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 11ß-HSD2 mRNA after RA treatment. Moreover, treatment with actinomycin D (100 ng/ml) abrogated the increase in 11ß-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 11ß-HSD2 gene expression and enzyme activity in JEG-3 cells. If this occurs in vivo, the present finding suggests that high expression of 11ß-HSD2 in the human placenta may be maintained, at least in part, by dietary intake of vitamin A.

¹ This work was supported by the Canadian MRC (Grant MT-12100 to K.Y.). K.Y. is an Ontario Ministry of Health Career Scientist.

² Correspondence: K. Yang, Lawson Research Institute, 268 Grosvenor Street, London, ON, Canada N6A 4V2. FAX: 519 646 6110; kyang{at}julian.uwo.ca

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