title: Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals.
abstract: We performed the Hershberger assay of 12 chemicals based on the OECD draft protocol. The chemicals tested by the Hershberger assay were phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, phthalic acid di-n-propyl ester, diethylstilbestrol, 17beta-estradiol, tamoxifen, 5alpha-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, atrazine, and spironolactone. Phthalic acid di-n-hexyl ester, phthalic acid di-n-amyl ester, and phthalic acid di-n-propyl ester are phthalates; diethylstilbestrol and 17beta-estradiol are estrogenic chemicals; tamoxifen is partial estrogen receptor antagonist with mainly estrogenic properties; 5alpha-dihydrotestosterone is an androgen derivatives; dichlorodiphenyldichloroethane is a reference androgen antagonistic chemical; cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, and spironolactone have an androgenic steroid structure and are known as androgen antagonistic chemicals; and atrazine is a reference endocrine disruptor. We also subjected these chemicals to the receptor binding assay for androgen. A clear androgen agonistic effect was detected in 5alpha-dihydrotestosterone, and an androgen antagonistic effect was observed in five chemicals: cyproterone acetate, spironolactone, 6alpha-methyl-17alpha-hydroxy-progesterone, phthalic acid di-n-amyl ester, and dichlorodiphenyldichloroethane. By contrast, diethylstilbestrol, 17beta-estradiol, tamoxifen, 5alpha-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6alpha-methyl-17alpha-hydroxy-progesterone, and spironolactone were positive in the receptor binding assay for androgen. Three estrogenic chemicals, diethylstilbestrol, 17beta-estradiol, and tamoxifen, were negative in the Hershberger assay with receptor binding affinity. On the other hand, the Hershberger assays of three phthalates were performed at the same dosages, and the results showed androgen antagonistic affinity only in the assay of phthalic acid di-n-amyl ester without receptor binding affinity.
authors.affiliation: Chemicals Assessment Center, Chemicals Evaluation and Research Institute, 3-822, Ishii, Hita, Oita 877-0061, Japan. yamasaki-kanji@ceri.jp
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Masakuni
authors.initials: M
authors.lastname: Sawaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Noda
authors.forename: Takako
authors.initials: T
authors.lastname: Muroi
authors.forename: Saori
authors.initials: S
authors.lastname: Takakura
authors.forename: Hideo
authors.initials: H
authors.lastname: Mitoma
authors.forename: Satoko
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakai
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yakabe
mesh_terms: D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects*; D008024:Ligands; D008297:Male; D009919:Orchiectomy; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D008024:Ligands; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins