Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male assay for detection of flutamide's antiandrogenic activity

Citation
T. Yamada et al., Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male assay for detection of flutamide's antiandrogenic activity, TOXICOL SCI, 53(2), 2000, pp. 289-296
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
1096-6080 → ACNP
Volume
53
Issue
2
Year of publication
2000
Pages
289 - 296
Database
ISI
SICI code
1096-6080(200002)53:2<289:CEOA5H>2.0.ZU;2-R
Abstract
A 5-day Hershberger assay utilizing mature male rats and a pubertal male as say were evaluated for the ability to detect antiandrogenic compounds such as flutamide, an androgen receptor antagonist. Six days after the operation , implantation with two silicon capsules containing testosterone (T) (30 mg /capsule) in castrated rats provided the ventral prostate and seminal vesic le weights as well as serum T and luteinizing hormone (LH) levels equivalen t to those of the controls (non-castrated, non-implanted rats). Castrated r ats implanted with two T-capsules (6 rats/dose) were treated by gavage for 5 days with vehicle (0.5% carboxymethylcellulose) or flutamide (0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles and the levator ani plus bulbocavernosus muscles (g reater than or equal to 0.6 mg/kg/day) and ventral prostate (greater than o r equal to 2.5 mg/kg/day), and an increase in serum LH levels (greater than or equal to 2.5 mg/kg/day), but no changes in serum T levels. When age-mat ched intact male rats were treated with 10-mg/kg/day flutamide, a significa nt increase in serum T levels was observed concomitant with a tendency of i ncreased LH. The organ weights were also decreased; however, the changes we re less than those in the castrated, T-implanted rats. Immature intact male rats (10 rats/dose) were treated for 20 days with flutamide (0, 0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles, ventral prostate, and levator ani plus bulbocaver nosus muscles at 2.5 and 10 mg/kg/day. Serum LH levels, but not T levels, w ere increased at 10 mg/kg/day. Statistical significance of some of these ch anges was not observed in the 6 animals/dose examined. Our findings support that the Hershberger assay, in the current conditions, is the most sensiti ve among the assays examined and a useful short-term screening method for t he detection of antiandrogenic compounds.