Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells. Issue 155 (January 2016)

• Record Type: Journal Article
• Authors: Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 155 Part B(2016)
• Page Start: 190
• Page End: 198
• Publication Date: 2016-01
• Subjects: 3β-HSD I 3β-hydroxysteroid dehydrogenase type I -- CL corpus luteum -- DBT dibutyltin -- DMSO dimethyl sulfoxide -- FCS fetal calf serum -- hCG human chorionic gonadotropin -- GR glucocorticoid receptor -- LG LG100268 -- LUC luciferase -- MEM minimal essential medium -- PPAR peroxisome proliferator-activated receptor -- RXR retinoid X receptor -- RT-PCR reverse transcription polymerase chain reaction -- Rosi rosiglitazone -- siRNA small interfering RNA -- TBT tributyltin -- TPT triphenyltin; Tributyltin (TBT) -- Triphenyltin (TPT) -- 3β-Hydroxysteroid dehydrogenase type I -- Placenta -- PPARγ; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.10.010
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Organotins promoted progesterone production in Jar cells by inducing 3β-HSD I mRNA. PPARγ knockdown blocked 3β-HSD mRNA transcription induced by PPARγ and RXR agonists. The PPARγ–RXR heterodimer may regulate 3β-HSD expression in human placenta. Effects of some organotin compounds correlated with their PPARγ agonistic activity. 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. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30–100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2 . These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women.