Human
choriocarcinoma cell lines have been used as placental models for the study of endocrine function, including
aromatase (
CYP19) activity and the secretion of human CG (hCG). In the present study, we investigated the effects of
trialkyltin compounds, which are suspected endocrine disrupters, on
aromatase activity and hCG secretion in human
choriocarcinoma JAR, JEG-3, and BeWo cells.
Protein synthesis as measured by (35)S-methionine incorporation in all cell lines was markedly decreased by treatment with both
tributyltin (TBT) and
triphenyltin (
TPT) at concentrations above 3 x 10(-7) M, due to cytotoxicity. In JAR cells, (35)S-methionine uptake was decreased by 50% at 3 x 10(-7) M of TBT. At a
TPT concentration of 1 x 10(-7) M,
protein synthesis in JAR cells was not affected, whereas JEG-3 and BeWo cells demonstrated slightly decreases. In all cell lines, both TBT and
TPT increased levels of hCG secretion and
aromatase activity in a dose- and time-dependent fashion following exposure to nontoxic concentration ranges. In addition, these
trialkyltin compounds enhanced 8-bromo-cAMP-induced hCG secretion and
aromatase activity in JAR cells. TBT caused dose-related increases in steady-state
mRNA levels of both hCGbeta and
CYP19 in JAR cells following 24- or 48-h exposure to nontoxic concentrations of TBT. However, these
mRNA changes in JAR cells were not comparable to the changes in both hCG secretion and
aromatase activity. These results indicate that the observed trialkyltin-induced alterations in human
choriocarcinoma cells are due to other mechanism in addition to a regulation of hCG and
CYP19 mRNA levels. Our studies suggest that
trialkyltin compounds are potent stimulators of human placental hCG production and
aromatase activity in vitro; and the placenta represents a potential target organ for
trialkyltin compounds, whose endocrine-disrupting effects might be the result of local changes in hCG and
estrogen concentrations in pregnant women.