Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-11-15
pubmed:abstractText
The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Androstenedione, http://linkedlifedata.com/resource/pubmed/chemical/Aromatase, http://linkedlifedata.com/resource/pubmed/chemical/Aromatase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Estradiol, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/Organotin Compounds, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Trialkyltin Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Water Pollutants, Chemical, http://linkedlifedata.com/resource/pubmed/chemical/tributyltin, http://linkedlifedata.com/resource/pubmed/chemical/triphenyltin
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
198-204
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11708799-Androstenedione, pubmed-meshheading:11708799-Animals, pubmed-meshheading:11708799-Apoptosis, pubmed-meshheading:11708799-Aromatase, pubmed-meshheading:11708799-Aromatase Inhibitors, pubmed-meshheading:11708799-Bucladesine, pubmed-meshheading:11708799-Cell Division, pubmed-meshheading:11708799-Disorders of Sex Development, pubmed-meshheading:11708799-Enzyme Inhibitors, pubmed-meshheading:11708799-Estradiol, pubmed-meshheading:11708799-Female, pubmed-meshheading:11708799-Genes, Reporter, pubmed-meshheading:11708799-Granulosa Cells, pubmed-meshheading:11708799-Humans, pubmed-meshheading:11708799-Luciferases, pubmed-meshheading:11708799-Male, pubmed-meshheading:11708799-Mollusca, pubmed-meshheading:11708799-Organotin Compounds, pubmed-meshheading:11708799-RNA, Messenger, pubmed-meshheading:11708799-Trialkyltin Compounds, pubmed-meshheading:11708799-Tumor Cells, Cultured, pubmed-meshheading:11708799-Water Pollutants, Chemical
pubmed:year
2001
pubmed:articleTitle
Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.
pubmed:affiliation
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
pubmed:publicationType
Journal Article