Retinoic acid stimulates the expression of 11beta-hydroxysteroid dehydrogenase type 2 in human choriocarcinoma JEG-3 cells.

Abstract

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.

• Authors: J Tremblay, D B Hardy, L E Pereira, K Yang
• Journal: Biology of reproduction (Biol Reprod) Vol. 60 Issue 3 Pg. 541-5 (Mar 1999) ISSN: 0006-3363 [Print] United States
• PMID: 10026096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Nucleic Acid Synthesis Inhibitors
• Dactinomycin
• Tretinoin
• Hydroxysteroid Dehydrogenases
• 11-beta-Hydroxysteroid Dehydrogenases

Topics

• 11-beta-Hydroxysteroid Dehydrogenases
• Choriocarcinoma (enzymology)
• Dactinomycin (pharmacology)
• Gene Expression (drug effects)
• Humans
• Hydroxysteroid Dehydrogenases (genetics)
• Isoenzymes (genetics)
• Nucleic Acid Synthesis Inhibitors (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Tretinoin (pharmacology)
• Tumor Cells, Cultured