Your browser doesn't support javascript.
loading
Organotin compounds act as inhibitor of transcriptional activation with human estrogen receptor.
Cho, Eun-Min; Lee, Haeng-Seog; Moon, Jeong-Suk; Kim, Im-Soon; Sim, Sanghyo; Ohta, Akinori.
Afiliación
  • Cho EM; New and Renewable Energy Company, North of Gyeonggi Venture Center, Uijongbu, Gyeonggi-do 480-020, Korea.
J Microbiol Biotechnol ; 22(3): 378-84, 2012 Mar.
Article en En | MEDLINE | ID: mdl-22450794
In aquatic invertebrates, particularly marine gastropods, organotin compounds induce irreversible sexual abnormality in females, which is termed imposex, at very low concentrations. Organotin compounds are agonists for nuclear receptors such as RXRs and PPARgamma. However, the imposex phenomenon has not been reported to act as an antagonist on estrogen receptors in other species, including vertebrates and invertebrates. In order to gain insights into the antagonistic activity of organotin compounds on estrogen receptors (ERs), we examined the inhibitive effect of these compounds on estradiol-dependent beta-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor (hERbeta) ligand-binding domain and the co-activator steroid receptor co-activator-1 (SRC1). Tributyltin-hydroxide (TBT-OH) and triphenyltin-chlorine (TPT-Cl) exhibited an inhibitive effect on E2-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of 10⁻¹4 M TBT or 10⁻¹° M TPT, respectively. The yeast growth and transcriptional activity with transcriptional factor GAL4 did not exhibit any effect at the tested concentration of TBT or TPT. Moreover, the yeast two-hybrid system using the interaction between p53 and the T antigen of SV40 large did not describe any effect at the tested concentration of OHT or ICI 182,780. However, the interaction between p53 and T antigen was inhibited at a TBT or TPT concentration of 10⁻9 M, respectively. These results indicate that TBT and TPT act as inhibitors of ER-dependent reporter gene transcriptional activation and of the interaction between hERbeta LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compound-induced imposex on the endocrine system of mammals, including humans.
Asunto(s)
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Orgánicos de Estaño / Compuestos de Trialquiltina / Receptores de Estrógenos / Regulación hacia Abajo / Activación Transcripcional / Trastornos Ovotesticulares del Desarrollo Sexual Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Microbiol Biotechnol Año: 2012 Tipo del documento: Article Pais de publicación: Corea del Sur
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Orgánicos de Estaño / Compuestos de Trialquiltina / Receptores de Estrógenos / Regulación hacia Abajo / Activación Transcripcional / Trastornos Ovotesticulares del Desarrollo Sexual Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: J Microbiol Biotechnol Año: 2012 Tipo del documento: Article Pais de publicación: Corea del Sur