title: Hormonal activity of polycyclic musks evaluated by reporter gene assay.
abstract: Synthetic musk fragrance compounds, such as polycyclic musks (PCMs), are a group of chemicals used extensively as personal care products, and can be found in the environment and the human body. PCMs, such as 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexa-methylcyclopenta-gamma-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyltetralin (AHTN), are known to have agonistic activities toward human estrogen receptor alpha (hERalpha) and hERbeta, and have antagonistic activity toward the human androgen receptor (hAR), as shown in several reporter gene assays. However, little is known about the interaction of PCMs with the human thyroid hormone receptor (hTR), and the hormonal effects of other PCMs except for HHCB and AHTN. In this study, we focus on the interactions of six PCMs, namely, HHCB, AHTN, 4-acetyl-1,1-dimethyl-6-tert-butyl-indan (ADBI), 6-acetyl-1,1,2,3,3,5-hexamethylindan (AHMI), 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanone (DPMI), and 5-acetyl-1,1,2,6-tetramethyl-3-isopropy-lindan (ATII) with hERalpha, hAR, and hTRbeta by in vitro reporter gene assay using Chinese hamster ovary cells. All the samples were found to be agonists toward hERalpha, whereas no agonistic activities of these PCMs for hAR and hTRbeta were observed. No antagonistic activities for hERalpha and hTRbeta were observed at the concentrations tested. However, several PCMs, namely, HHCB, AHTN, ATII, ADBI, and AHMI, showed dose-dependent antagonistic activities for hAR, and the IC50 values of these compounds were estimated to be 1.0 x 10(-7), 1.5 x 10(-7), 1.4 x 10(-7), 9.8 x 10(-6), and 1.4 x 10(-7) M, respectively. The results suggest that these PCMs interact with hERalpha and hAR but have no hormonal effect on hTRbeta. This is the first report on the agonistic and antagonistic activities of ATII, ADBI, AHMI, and DPMI for hERalpha and hAR as determined by in vitro reporter gene assay using stably transfected Chinese hamster ovary cells.
authors.affiliation: Graduate School of Science and Technology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Mori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Iida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Kohra
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takao
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takemasa
authors.forename: Koji
authors.initials: K
authors.lastname: Arizono
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001681:Biological Assay; D016466:CHO Cells; D003358:Cosmetics; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors; D005229:Fatty Acids, Monounsaturated; D005260:Female; D017930:Genes, Reporter; D007189:Indans / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D003358:Cosmetics; D047628:Estrogen Receptor alpha; D005229:Fatty Acids, Monounsaturated; D007189:Indans; D011944:Receptors, Androgen; D011988:Receptors, Thyroid Hormone; D013764:Tetrahydronaphthalenes; C008563:musk; C033119:galaxolide; C033116:acetyl methyl tetramethyl tetralin