Concept evaluation: androgen-stimulated immature intact male rats as an assay for antiandrogens.
The effects of the concomitant oral administration of a potent reference androgen (17alpha-methyltestosterone) and both a potent (flutamide) and a weak (p,p'-DDE) antiandrogen on intact weanling male rats are described. This protocol resulted in the inhibition by the antiandrogens of the increase in sex accessory tissue weights induced by coadministration of 17alpha-methyltestosterone. Although both flutamide and p,p'-DDE inhibited the androgen-induced growth of the levator ani/bulbocavernosus muscle complex, the Cowper's glands, and the seminal vesicles, the growth of the prostate gland was unaffected by either antiandrogen. The unresponsiveness of the prostate gland, a primary target tissue in the castrated rat antiandrogen assay, has yet to be fully explained. However, the ability of the assay to detect the activity of low dose levels of the weak antiandrogen DDE (at doses of 20 mg/kg body weight) makes the system worthy of further study as one of several alternatives. Given the rapid rate of assay/protocol exploration and refinement of this assay and its alternatives, there is the need for careful comparative studies before selecting a single bioassay for validation and regulatory use.
Ashby
John
J
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. John.Ashby@Syngenta.com
Owens
W
W
Lefevre
P A
PA
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002985:Clinical Protocols; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005485:Flutamide / Q000494:pharmacology*; D005837:Genitalia, Male / Q000187:drug effects*; D008297:Male; D008777:Methyltestosterone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation
D000726:Androgen Antagonists; D000728:Androgens; D003633:Dichlorodiphenyl Dichloroethylene; D005485:Flutamide; D008777:Methyltestosterone