Organotin compounds, such as
tributyltin (TBT) and
triphenyltin (
TPT), are typical environmental contaminants and suspected
endocrine-disrupting chemicals because they cause masculinization in female mollusks. However, it remains unclear whether
organotin compounds also cause crucial toxicities in human sexual development and reproductive functions. We investigated the effects of 17
tin compounds on the catalytic activity and
mRNA expression of
17beta-hydroxysteroid dehydrogenase type I (17beta-HSD I) in human
choriocarcinoma JAr cells. At nontoxic concentrations, both trialkyltins with propyl, butyl or cyclohexyl substituents on the
tin atom and
triphenyltin (
TPT) enhanced 17beta-HSD I
mRNA transcription and
enzyme activity in a dose-dependent fashion. Although tetraalkyltin compounds such as
tetrabutyltin and tributylvinyltin also increased the
mRNA expression and
enzyme activity of 17beta-HSD I, the concentrations necessary for activation were >30-100 times greater than those for trialkyltins. Inorganic
tin had no effect on the catalytic activity and
mRNA expression of 17beta-HSD I. Interestingly,
diphenyltin and
monophenyltin, which are metabolites of
TPT, enhanced 17beta-HSD I activity with a concomitant increase in
mRNA expression, whereas
dibutyltin and
monobutyltin, which are metabolites of
tributyltin, enhanced 17beta-HSD I activity without a concomitant increase in
mRNA expression. These results suggest that
organotin compounds are potent stimulators of 17beta-estradiol biosynthesis to enhance 17beta-HSD I activity in the human placenta in vitro; the placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might be the result of local changes in 17beta-estradiol concentrations in pregnant women.