Effect of cadmium on cortisol production and 11beta-hydroxysteroid dehydrogenase 2 expression by cultured human choriocarcinoma cells (JEG-3).
Cadmium is a toxicant with known carcinogenic and endocrine disruptor effects. We have previously reported that prenatal exposure to cadmium may induce low birth weight which is associated to increased foetal exposure to glucocorticoids; both signals constitute "hallmarks" of developmental programming. Since the effect of cadmium on the glucocorticoid system of placental carcinogenic cells is unknown, in the present work, we studied the effect of acute low dose of cadmium on cortisol production and 11beta-HSD2 expression and activity by cultured human choriocarcinoma cells (JEG-3). In addition, it was also evaluated whether those effects were related to the methylation index of the HSD11B2 gene, which can be regulated by epigenetic mechanisms. Cells were incubated with low cadmium dose (0.5 and 1 microM) for 24h and viability (MTT), cortisol production (EIA), 11beta-HSD2 expression (qRT-PCR) and activity (radioassay), and methylation index of the HSD11B2 gene were determined. Results show lower cortisol concentrations in the incubation media of exposed cells, which were associated to increased 11beta-HSD2 expression and activity and to a lower methylation index of the gene. These results suggest that cadmium-induced endocrine disruptor effects on JEG-3 cells could be mediated by changes in the methylation status of some target genes.
Ronco
Ana Maria
AM
Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago, Chile. amronco@inta.cl
Llaguno
Emanuel
E
Epuñan
Maria Jose
MJ
Llanos
Miguel N
MN
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D019187:Cadmium Compounds / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D019187:Cadmium Compounds; D004785:Environmental Pollutants; D012333:RNA, Messenger; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone