Endocrinology 2017

In June 2017, Bilal Mughal, Jean-Baptiste Fini, Barbara Demeneix and colleagues (Muséum National d'Histoire Naturelle, CNRS, Paris, France) published a paper in Endocrinology.

 

Mughal BB, Leemans M, L de Souza EC, le Mevel S, Spirhanzlova P, Visser T, Fini JB, Demeneix BA. Functional characterisation of Xenopus thyroid hormone transporters mct8 and oatp1c1. Endocrinology. 2017 Jun 7. doi: 10.1210/en.2017-00108.

 

Abstract

Xenopus is an excellent model for studying thyroid hormone signalling as it undergoes thyroid hormone-dependent metamorphosis. Despite the fact that receptors and deiodinases have been described in Xenopus, membrane transporters for these hormones are yet to be characterised. We cloned Xenopus monocarboxylate transporter 8 (mct8) and organic anion transporting polypeptide 1C1 (oatpc1c1), focusing on these two transporters given their importance for vertebrate brain development. Protein alignment and bootstrap analysis showed that Xenopus mct8 and oatp1c1 are closer to their mammalian orthologues than their teleost counterparts. We functionally characterised the two transporters using a radiolabelled hormones in vitro uptake assay in COS-1 cells. Xenopus mct8 was found to actively transport both T3 and T4 bi-directionally. As to the thyroid precursor molecules, DIT and MIT, both human and Xenopus mct8 showed active efflux, but no influx. Again similar to humans, Xenopus oatp1c1 transported T4 but not T3, MIT or DIT. We used RT-qPCR and in situ hybridisation to characterise the temporal and spatial expression of mct8 and oatp1c1 in Xenopus. Specific expression of the transporter was observed in the brain, with increasingly strong expression as development progressed. In conclusion, these results show that Xenopus thyroid hormone transporters are functional and display marked spatio-temporal expression patterns. These features make them interesting targets to elucidate their roles in determining thyroid hormone availability during embryonic development.