PT07 Chemical and Biological Analysis of Endocrine Disrupting Compounds
Exhibit Hall
8:00 AM - Tuesday
(PT101) Involvement of the Retinoid X Receptor in the Imposex Development Caused by Organotins in Gastropods.
Horiguchi, T.1, Nishikawa, T.1, Ohta, Y.2, Mamiya, S.3, Kanayama, T.3, Shiraishi, F.1, Shiraishi, H.1, Morita, M.1, Nishikawa, J.3, 1 National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan2 School of Veterinary Medicine, Tottori University, Tottori, Tottori, Japan3 Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan
ABSTRACT- Organotin compounds released from antifouling paints, such as tributyltin (TBT) and triphenyltin (TPhT), are accepted to be potent inducers of imposex (a superimposition of male genital tracts, such as penis and vas deferens, on females) in marine gastropods. Little is known about the induction mechanism of gastropod imposex although several hypotheses have been proposed. Here, we show that organotins bind the human retinoid X receptors (hRXRs) with high affinity, and that injection of 9-cis retinoic acid (RA), the natural ligand of hRXRs into females of the rock shell (Thais clavigera) induces the development of imposex. Cloning of the RXR homologue from Thais clavigera revealed that the ligand-binding domain of rock shell RXR was very similar to vertebrate RXR and bound to both 9-cis RA and to organotins. Injection experiments of 9-cis RA resulted in inducing and promoting the development of imposex in the rock shell, with a dose-dependent manner. These suggest that RXR plays an important role in inducing the development of imposex, namely the differentiation and growth of male genital tracts in female gastropods.
Key words: imposex, retinoid X receptor (RXR), Thais clavigera, organotins