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Possible Involvement of Organic Anion Transporting Polypeptide 1c1 in the Photoperiodic Response of Gonads in Birds

Division of Biomodeling, Graduate School of Bioagricultural Sciences (N.N., T.Ta., S.Y., S.E., T.Yo.), Institute for Advanced Research (T.Yo.), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; and Department of Applied Biochemistry, Faculty of Agriculture (M.I., T.M., T.Ya.), Genomics Research Institute (T.Ts.), Utsunomiya University, Mine-machi, Utsunomiya, Tochigi 321-8505, Japan

Address all correspondence and requests for reprints to: Takashi Yoshimura, Ph.D., Division of Biomodeling, Graduate School of Bioagricultural Sciences, and Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. E-mail: takashiy{at}agr.nagoya-u.ac.jp.

The photoperiodic response of the gonads requires T₃, which is generated photoperiodically from T₄ by type 2 iodothyronine deiodinase in the hypothalamus. Although thyroid hormones were long thought to traverse the plasma membrane by passive diffusion due to their lipophilic nature, it is now known that several organic anion transporting polypeptides (Oatp) transport thyroid hormones into target cells. In this study, we have used database searches to isolate DNA sequences encoding members of the chicken Oatp family and constructed a molecular phylogenetic tree. Comprehensive expression analyses using in situ hybridization revealed strong expression of cOatp1c1 and weak expression of cOatp1b1 in the ventro-lateral walls of basal tuberal hypothalamus, whereas expression of four genes (cOatp1a1, cOatp1b1, cOatp1c1, and cOatp3a2) was observed in the choroid plexus. Expression levels of all these genes in both regions were not different between short-day and long-day conditions. Functional expression of cOatp1c1 in Chinese hamster ovary cells revealed that cOatp1c1 is a highly specific transporter for T₄ with an apparent Km of 6.8 nM and a Vmax of 1.50 pmol per milligram of protein per minute. These results suggest that cOatp1c1 could be involved in the thyroxine transport necessary for the avian photoperiodic response of the gonads.

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