Application of an androgen receptor assay for the characterisation of the androgenic or antiandrogenic activity of various phenylurea herbicides and their derivatives.
The potency of different substances for [3H]dihydrotestosterone ([3H]DHT) displacement from the bovine androgen receptor was tested. The phenylurea herbicide linuron and its derivative 3,4-dichloroaniline (3,4-DCA), which are found in sediments and surface waters, are known to displace bound testosterone from the rat androgen receptor. Because 3,4-DCA is rapidly taken up by fish and metabolised into 3,4-dichloroacetanilide (3,4-DCAc), it was investigated whether the displacement effects are attributable to 3,4-DCA or to 3,4-DCAc. The potency of 3,4-DCAc androgen receptor binding was compared with that of several phenylurea compounds. In a radioreceptor assay with calf uterus cytosol as androgen receptor preparation, the specific binding of [3H]DHT, the endogenous ligand, was completely displaceable by increasing concentrations of 3,4-DCAc. The relative binding affinities (RBA) of the various compounds were about 1/10(4) to 1/10(5) of that of DHT. 3,4-DCAc had the relative highest affinity (1.31 x 10(-4)), followed by linuron, 3,4-dichlorophenylurea, flutamide, 3,4-DCA and diuron with the lowest RBA (2.4 x 10(-5)). Hence the metabolism of xenobiotic compounds has to be considered to estimate potential ecotoxiocological effects. This test not only can be used to screen for androgen- and antiandrogen-like substances in environmentally relevant samples such as surface waters, but might also be applied for drug testing and for residue monitoring.
Bauer
E R
ER
Institute of Physiology, Research Center for Milk and Food, Weihenstephan, Germany.
Meyer
H H
HH
Stahlschmidt-Allner
P
P
Sauerwein
H
H
D000083:Acetanilides / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D002417:Cattle; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D006540:Herbicides / Q000494:pharmacology*; D008044:Linuron / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011869:Radioligand Assay; D011944:Receptors, Androgen / Q000378:metabolism*
D000083:Acetanilides; D000814:Aniline Compounds; D006540:Herbicides; D010671:Phenylurea Compounds; D011944:Receptors, Androgen; D008044:Linuron; D013196:Dihydrotestosterone; C014464:3,4-dichloroaniline; C120976:3,4-dichloroacetanilide