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Organotin compounds enhance 17beta-hydroxysteroid dehydrogenase type I activity in human choriocarcinoma JAr cells: potential promotion of 17beta-estradiol biosynthesis in human placenta.

Abstract
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.
AuthorsTsuyoshi Nakanishi, Youhei Hiromori, Hideaki Yokoyama, Mihoko Koyanagi, Norio Itoh, Jun-Ichi Nishikawa, Keiichi Tanaka
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 71 Issue 9 Pg. 1349-57 (Apr 28 2006) ISSN: 0006-2952 [Print] England
PMID16513093 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Organotin Compounds
  • RNA, Messenger
  • Tritium
  • Estradiol
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Thymidine
Topics
  • 17-Hydroxysteroid Dehydrogenases (genetics, metabolism)
  • Cell Line, Tumor
  • Choriocarcinoma
  • Estradiol (biosynthesis)
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Organotin Compounds (toxicity)
  • Placenta (metabolism)
  • RNA, Messenger (metabolism)
  • Thymidine (metabolism)
  • Tritium

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