The organic anion transporting polypeptide 1a5 is a pivotal transporter for the uptake of microcystin-LR by gonadotropin-releasing hormone neurons

Abstract Microcystins (MCs) are widely distributed hepatotoxic polypeptides produced by cyanobacteria. Microcystin-LR (MC-LR) has the broadest distribution and strongest toxicity among more than 80 isoforms of hepatotoxic MCs. MC-LR suppresses the expression of gonadotropin-releasing hormone (GnRH) that is critically required for the release of testosterone, resulting in the induction of male reproductive toxicity. However, the specific mechanisms of the uptake of MC-LR by GnRH-secreting neurons still remain unclear. In this study, GT1-7 cells were exposed to MC-LR in order to determine whether the GnRH-secreting neurons were the target of MC-LR that could induce male reproductive toxicity. Our data demonstrated that at least four organic anion transporting polypeptides (Oatp1a4, Oatp1a5, Oatp5a1, Oatp2b1) were expressed in GnRH neurons at the mRNA level, but only Oatp1a5 was expressed at the protein level. Furthermore, we demonstrated that MC-LR could not be transported into Oatp1a5-deficient GT1-7 cells which were protected from cell viability loss induced by MC-LR. These data suggest that Oatp1a5 may play an important role in the toxic effect of MC-LR on GnRH neurons.