Source:http://linkedlifedata.com/resource/pubmed/id/10496676
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
1999-10-15
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| pubmed:abstractText |
In this report, p,p'-DDE, a weak androgen receptor (AR) antagonist, has been examined in a Tier I screening battery designed to detect endocrine-active compounds (EACs). The screening battery that was used to examine p,p'-DDE was an abbreviated version of a proposed Tier I screening battery (Cook et al., 1997, Regul. ToxicoL Pharmacol. 26, 60-68) that consisted of a 15-day intact male in vivo battery and an in vitro yeast transactivation system (YTS). In addition, strain sensitivity differences were evaluated using male Crl:CDIGS BR (CD) and Long-Evans (LE) rats. Finally, p,p'-DDE was examined in a Hershberger assay designed to detect AR agonists. In the in vivo male battery using CD rats, responses to p,p'-DDE included organ weight changes (increased relative liver weight and decreased absolute epididymis weight) and hormonal alterations (increased serum estradiol [E2] levels and decreased serum FSH and T4 levels). Responses to p,p'-DDE in LE rats included organ weight changes (increased relative liver weight, absolute epididymis weight, relative accessory sex gland [ASG] unit weight, as well as the individual component weights of the ASG [prostate and seminal vesicles]), and hormonal alterations (increased serum testosterone [T], E2, dihydrotestosterone [DHT], thyroid-stimulating hormone [TSH], and decreased T4 levels). These data demonstrate that there are considerable strain-sensitivity differences to p,p'-DDE exposure. The described in vivo male battery using CD rats did not identify p,p'-DDE as an EAC. In contrast, the in vivo male battery using LE rats identified p,p'-DDE as a EAC. Evaluation of the data for the LE rats demonstrate that p,p'-DDE appears to be acting as an AR antagonist whose primary effects are more potent centrally than peripherally. In the YTS for the AR, p,p'-DDE had an EC50 value of 3.5 x 10(-4) M; however, in the AR YTS competition assay, p,p'-DDE did not inhibit DHT binding to the AR. p,p'-DDE was inactive in the YTS containing the estrogen receptor or progesterone receptor at the concentrations evaluated. In the Hershberger assay, p,p'-DDE administration caused antiandrogen-like effects characterized by attenuation of the testosterone propionate-induced increases in reproductive-organ weights. In summary, these data suggest that strain selection will affect the ability to detect certain weak EACs. However, a Tier I screening battery consisting of both in vivo and in vitro endpoints would reduce the chance that weak-acting compounds such as p,p'-DDE would not be identified as potential EACs.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1096-6080
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
51
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
44-53
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| pubmed:dateRevised |
2010-9-17
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| pubmed:meshHeading |
pubmed-meshheading:10496676-Animals,
pubmed-meshheading:10496676-Body Weight,
pubmed-meshheading:10496676-Dichlorodiphenyl Dichloroethylene,
pubmed-meshheading:10496676-Disease Models, Animal,
pubmed-meshheading:10496676-Flutamide,
pubmed-meshheading:10496676-Gonadal Steroid Hormones,
pubmed-meshheading:10496676-Insecticides,
pubmed-meshheading:10496676-Liver,
pubmed-meshheading:10496676-Male,
pubmed-meshheading:10496676-Orchiectomy,
pubmed-meshheading:10496676-Organ Size,
pubmed-meshheading:10496676-Prostate,
pubmed-meshheading:10496676-Rats,
pubmed-meshheading:10496676-Rats, Long-Evans,
pubmed-meshheading:10496676-Saccharomyces cerevisiae,
pubmed-meshheading:10496676-Seminal Vesicles,
pubmed-meshheading:10496676-Testis,
pubmed-meshheading:10496676-Toxicity Tests,
pubmed-meshheading:10496676-Transcriptional Activation
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| pubmed:year |
1999
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| pubmed:articleTitle |
Detection of the environmental antiandrogen p,p-DDE in CD and long-evans rats using a tier I screening battery and a Hershberger assay.
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| pubmed:affiliation |
DuPont Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714, USA. john.c.oconnor@usa.dupont.com
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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