Linked Life Data

8480329

Source:http://linkedlifedata.com/resource/pubmed/id/8480329

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-5-25
pubmed:abstractText
In a previously conducted 2-year study, a concentration-dependent increase in Leydig cell adenomas was observed in Crl:CD BR(CD) rats fed diets containing the herbicide linuron. Linuron has been shown to be negative in a battery of six tests for genotoxicity; therefore, a nongenotoxic mechanism of tumorgenesis was investigated. Linuron is structurally related to the nonsteroidal antiandrogen, flutamide. Flutamide has also been shown to produce Leydig cell tumors within 1 year, presumably due to sustained hypersecretion of luteinizing hormone (LH) which occurs following disruption of the hypothalamic-pituitary-testicular (HPT) axis. To investigate whether linuron possesses antiandrogenic activity, sexually immature and mature CD rats were administered either 200 mg/kg linuron or 10 mg/kg flutamide (positive control) for 2 weeks. Accessory sex organs were weighed and serum hormone levels were measured to assess androgen status and alterations in the HPT axis. Serum from a multigeneration reproduction study with linuron was also analyzed for serum hormone levels. In addition, competitive receptor binding studies were conducted to evaluate the ability of linuron to bind to the androgen receptor. Linuron decreased accessory sex organ weights in sexually immature and mature linuron-treated rats. Increased serum estradiol and LH levels were observed in sexually mature linuron-treated rats. Serum estradiol and LH levels were also elevated in P1 and F1 male rats from the multigeneration reproduction study. These accessory sex organ and hormonal changes are consistent with those seen with the antiandrogen flutamide, the only exception being serum testosterone, which was elevated following exposure to flutamide but not to linuron. The inability of linuron to increase testosterone levels may reflect the lower potency of linuron as an antiandrogen compared with that of flutamide, which is a potent antiandrogen. Additionally, linuron competed with [3H]testosterone for binding to the androgen receptor. The IC50 data for competition to the androgen receptor suggest that linuron is approximately 3.5 times less potent than flutamide. These data are consistent with the effects seen with flutamide and demonstrate that linuron is a less potent antiandrogen than flutamide. Collectively, these data support the hypothesis that linuron produces Leydig cell tumors via an antiandrogenic mechanism where sustained hypersecretion of LH appears to be responsible for the development of Leydig cell hyperplasia and adenomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-204
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8480329-Age Factors, pubmed-meshheading:8480329-Androgen Antagonists, pubmed-meshheading:8480329-Animals, pubmed-meshheading:8480329-Binding, Competitive, pubmed-meshheading:8480329-Body Weight, pubmed-meshheading:8480329-Cell Transformation, Neoplastic, pubmed-meshheading:8480329-Estradiol, pubmed-meshheading:8480329-Female, pubmed-meshheading:8480329-Flutamide, pubmed-meshheading:8480329-Genitalia, Male, pubmed-meshheading:8480329-Leydig Cells, pubmed-meshheading:8480329-Linuron, pubmed-meshheading:8480329-Luteinizing Hormone, pubmed-meshheading:8480329-Male, pubmed-meshheading:8480329-Organ Size, pubmed-meshheading:8480329-Pedigree, pubmed-meshheading:8480329-Rats, pubmed-meshheading:8480329-Rats, Inbred Strains, pubmed-meshheading:8480329-Receptors, Androgen, pubmed-meshheading:8480329-Testosterone
pubmed:year
1993
pubmed:articleTitle
Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats.
pubmed:affiliation
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours & Company, Newark, Delaware 19714.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't