Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals

• Published in: Toxicology (Amsterdam) Vol. 195; no. 2; pp. 177 - 186
• Main Authors: Yamasaki, Kanji, Sawaki, Masakuni, Noda, Shoji, Muroi, Takako, Takakura, Saori, Mitoma, Hideo, Sakamoto, Satoko, Nakai, Makoto, Yakabe, Yoshikuni
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.02.2004; Amsterdam Elsevier Science
• Subjects: Administration, Oral; Androgen Antagonists - administration & dosage; Androgen Antagonists - toxicity; Androgenic effect; Animals; Biological and medical sciences; Biological Assay; Body Weight - drug effects; Castration; Dose-Response Relationship, Drug; Endocrine; Estrogen Antagonists - administration & dosage; Estrogen Antagonists - toxicity; General aspects. Methods; Genitalia, Male - drug effects; Hershberger assay; Ligands; Male; Medical sciences; OECD draft protocol; Orchiectomy; Random Allocation; Rat; Rats; Rats, Inbred Strains; Receptor binding assay; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; Recombinant Fusion Proteins - metabolism; Toxicology; OECD draft protocol; Castration; Rat; Androgenic effect; Receptor binding assay; Endocrine; Hershberger assay; Chemical compound; Rodentia; Endocrine disruptor; Hershherger assay; Vertebrata; Mammalia; Investigation method; Animal; Comparative study; Biological receptor; Hormonal receptor
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2003.09.012

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, 17β-estradiol, tamoxifen, 5α-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6α-methyl-17α-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 17β-estradiol are estrogenic chemicals; tamoxifen is partial estrogen receptor antagonist with mainly estrogenic properties; 5α-dihydrotestosterone is an androgen derivatives; dichlorodiphenyldichloroethane is a reference androgen antagonistic chemical; cyproterone acetate, 6α-methyl-17α-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 5α-dihydrotestosterone, and an androgen antagonistic effect was observed in five chemicals: cyproterone acetate, spironolactone, 6α-methyl-17α-hydroxy-progesterone, phthalic acid di- n-amyl ester, and dichlorodiphenyldichloroethane. By contrast, diethylstilbestrol, 17β-estradiol, tamoxifen, 5α-dihydrotestosterone, dichlorodiphenyldichloroethane, cyproterone acetate, 6α-methyl-17α-hydroxy-progesterone, and spironolactone were positive in the receptor binding assay for androgen. Three estrogenic chemicals, diethylstilbestrol, 17β-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.