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Identification and Characterization of Novel Rat and Human Gonad-Specific Organic Anion Transporters

Division of Nephrology, Endocrinology, and Vascular Medicine (T.S., M.T., M.A., F.S., S.I., T.A.), Department of Medicine; Division of Gastroenterological Surgery (T.O., M.U., M.S., S.M.), Department of Surgery, Division of Gastroenterology (N.A., H.M., T.S.), Department of Medicine, Department of Molecular Pharmacology (K.N.), Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Clinical Pharmacy (T.M., T.H., J.G.), Tohoku University Graduate School of Pharmaceutical Sciences, Sendai 980-8575, Japan; and Precursory Research for Embryonic Science and Technology (T.A.), Japan Science and Technology Corporation, Saitama 332-0012, Japan

Address all correspondence and requests for reprints to: Takaaki Abe, Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. E-mail: takaabe{at}mail.cc tohoku.ac.jp.

We have isolated three novel organic anion transporter cDNAs designated rat GST-1 (gonad-specific transporter), rat GST-2, and human GST, expressed at high levels in the testis. Rat GST-1, GST-2, and human GST consist of 748, 702, and 719 amino acids, respectively, and all molecules possess the 12 predicted transmembrane domains, which is a common structure of organic anion transporters. Northern blot analyses and in situ hybridization revealed that both of the rat molecules are highly expressed in the testis, especially in Sertoli cells, spermatogonia, and Leydig cells. Weak signals are also detected in the epididymis and ovary in adult rat. The exclusive expression of human GST mRNA in the testis was confirmed by RT-PCR. The pharmacological experiments of Xenopus laevis oocytes injected with the respective rat GST-1- and GST-2-cRNAs revealed that both rat GST-1 and GST-2 transport taurocholic acid, dehydroepiandrosterone sulfate, and T₄ with Michaelis-Menten kinetics (taurocholic acid, K_m = 8.9 and 2.5 µM, dehydroepiandrosterone sulfate, K_m = 25.5 and 21.µM, and T₄, K_m = 6.4 and 5.8 for rat GST-1 and GST-2, respectively). T₃ was also transported by rat GST-1 and GST-2. These data suggest that rat GST-1 and GST-2 might be one of the molecular entities responsible for transporting dehydroepiandrosterone sulfate and thyroid hormones involved in the regulation of sex steroid transportation and spermatogenesis in the gonad.

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