This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by St-Pierre, M. V. Articles by Stallmach, T. Search for Related Content PubMed PubMed Citation Articles by St-Pierre, M. V. Articles by Stallmach, T.

Characterization of an Organic Anion-Transporting Polypeptide (OATP-B) in Human Placenta

Department of Medicine (M.V.S.-P., B.H., P.J.M.), Division of Clinical Pharmacology and Toxicology, and Department of Pathology (T.S.), Institute of Clinical Pathology, University Hospital, CH-8091 Zurich, Switzerland; and I. Frauenklinik Innenstadt (B.U.), Klinikum der Universität München, 80337 Munich, Germany

Address all correspondence and requests for reprints to: Marie V. St.-Pierre, Ph.D., Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zürich CH-8091, Switzerland. E-mail: . stpierre{at}kpt.unizh.ch

Abstract

Organic anion-transporting polypeptides (OATPs) are a family of multispecific carriers that mediate the sodium-independent transport of steroid hormone and conjugates, drugs, and numerous anionic endogenous substrates. We investigated whether members of the OATP gene family could mediate fetal-maternal transfer of anionic steroid conjugates in the human placenta. OATP-B (gene symbol SLC21A9) was isolated from a placenta cDNA library. An antiserum to OATP-B detected an 85-kDa protein in basal but not apical syncytiotrophoblast membranes. Immunohistochemistry of first-, second-, and third-trimester placenta showed staining in the cytotrophoblast membranes and at the basal surface of the syncytiotrophoblast. Trophoblasts that reacted with an antibody to Ki-67, a proliferation-associated antigen, expressed lower levels of OATP-B. OATP-B mRNA levels were measured in isolated trophoblasts under culture conditions that promoted syncytia formation. Real-time quantitative PCR estimated an 8-fold increase in OATP-B expression on differentiation to syncytia. The uptake of [³H]estrone-3-sulfate, a substrate for OATP-B, was measured in basal syncytiotrophoblast membrane vesicles. Transport was saturable and partially inhibited by pregnenolone sulfate, a progesterone precursor. Pregnenolone sulfate also partially inhibited OATP-B-mediated transport of estrone-3-sulfate in an oocyte expression system. These findings suggest a physiological role for OATP-B in the placental uptake of fetal-derived sulfated steroids.

This article has been cited by other articles:

				A. Mulenga, R. Khumthong, K. C. Chalaire, O. Strey, and P. Teel Molecular and biological characterization of the Amblyomma americanum organic anion transporter polypeptide J. Exp. Biol., November 1, 2008; 211(21): 3401 - 3408. [Abstract] [Full Text] [PDF]

				L. M. Aleksunes, Y. Cui, and C. D. Klaassen Prominent Expression of Xenobiotic Efflux Transporters in Mouse Extraembryonic Fetal Membranes Compared with Placenta Drug Metab. Dispos., September 1, 2008; 36(9): 1960 - 1970. [Abstract] [Full Text] [PDF]

				R. D. Huber, B. Gao, M.-A. Sidler Pfandler, W. Zhang-Fu, S. Leuthold, B. Hagenbuch, G. Folkers, P. J. Meier, and B. Stieger Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain Am J Physiol Cell Physiol, February 1, 2007; 292(2): C795 - C806. [Abstract] [Full Text] [PDF]

				M. Grube, S. Reuther, H. Meyer zu Schwabedissen, K. Kock, K. Draber, C. A. Ritter, C. Fusch, G. Jedlitschky, and H. K. Kroemer Organic Anion Transporting Polypeptide 2B1 and Breast Cancer Resistance Protein Interact in the Transepithelial Transport of Steroid Sulfates in Human Placenta Drug Metab. Dispos., January 1, 2007; 35(1): 30 - 35. [Abstract] [Full Text] [PDF]

				M. Grube, K. Kock, S. Karner, S. Reuther, C. A. Ritter, G. Jedlitschky, and H. K. Kroemer Modification of OATP2B1-Mediated Transport by Steroid Hormones Mol. Pharmacol., November 1, 2006; 70(5): 1735 - 1741. [Abstract] [Full Text] [PDF]

				E. Hanggi, A. F. Grundschober, S. Leuthold, P. J. Meier, and M. V. St-Pierre Functional Analysis of the Extracellular Cysteine Residues in the Human Organic Anion Transporting Polypeptide, OATP2B1 Mol. Pharmacol., September 1, 2006; 70(3): 806 - 817. [Abstract] [Full Text] [PDF]

				Y. Sai, Y. Kaneko, S. Ito, K. Mitsuoka, Y. Kato, I. Tamai, P. Artursson, and A. Tsuji PREDOMINANT CONTRIBUTION OF ORGANIC ANION TRANSPORTING POLYPEPTIDE OATP-B (OATP2B1) TO APICAL UPTAKE OF ESTRONE-3-SULFATE BY HUMAN INTESTINAL CACO-2 CELLS Drug Metab. Dispos., August 1, 2006; 34(8): 1423 - 1431. [Abstract] [Full Text] [PDF]

				H. Satoh, F. Yamashita, M. Tsujimoto, H. Murakami, N. Koyabu, H. Ohtani, and Y. Sawada CITRUS JUICES INHIBIT THE FUNCTION OF HUMAN ORGANIC ANION-TRANSPORTING POLYPEPTIDE OATP-B Drug Metab. Dispos., April 1, 2005; 33(4): 518 - 523. [Abstract] [Full Text] [PDF]

				M. Grube, H. M. z. Schwabedissen, K. Draber, D. Prager, K.-U. Moritz, K. Linnemann, C. Fusch, G. Jedlitschky, and H. K. Kroemer EXPRESSION, LOCALIZATION, AND FUNCTION OF THE CARNITINE TRANSPORTER OCTN2 (SLC22A5) IN HUMAN PLACENTA Drug Metab. Dispos., January 1, 2005; 33(1): 31 - 37. [Abstract] [Full Text] [PDF]

				H. E.U. Meyer zu Schwabedissen, M. Grube, B. Heydrich, K. Linnemann, C. Fusch, H. K. Kroemer, and G. Jedlitschky Expression, Localization, and Function of MRP5 (ABCC5), a Transporter for Cyclic Nucleotides, in Human Placenta and Cultured Human Trophoblasts: Effects of Gestational Age and Cellular Differentiation Am. J. Pathol., January 1, 2005; 166(1): 39 - 48. [Abstract] [Full Text] [PDF]

				T. Nozawa, M. Suzuki, K. Takahashi, H. Yabuuchi, T. Maeda, A. Tsuji, and I. Tamai Involvement of Estrone-3-Sulfate Transporters in Proliferation of Hormone-Dependent Breast Cancer Cells J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 1032 - 1037. [Abstract] [Full Text] [PDF]

				M. V. St-Pierre, T. Stallmach, A. Freimoser Grundschober, J.-F. Dufour, M. A. Serrano, J. J. G. Marin, Y. Sugiyama, and P. J. Meier Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1505 - R1516. [Abstract] [Full Text] [PDF]

				T. Nozawa, K. Imai, J.-I. Nezu, A. Tsuji, and I. Tamai Functional Characterization of pH-Sensitive Organic Anion Transporting Polypeptide OATP-B in Human J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 438 - 445. [Abstract] [Full Text] [PDF]

				F. Zhou, K. Tanaka, M. J. Soares, and G. You Characterization of an organic anion transport system in a placental cell line Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1103 - E1109. [Abstract] [Full Text] [PDF]

				N. Mizuno, T. Niwa, Y. Yotsumoto, and Y. Sugiyama Impact of Drug Transporter Studies on Drug Discovery and Development Pharmacol. Rev., September 1, 2003; 55(3): 425 - 461. [Abstract] [Full Text] [PDF]

				F. Pizzagalli, Z. Varga, R. D. Huber, G. Folkers, P. J. Meier, and M. V. St-Pierre Identification of Steroid Sulfate Transport Processes in the Human Mammary Gland J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3902 - 3912. [Abstract] [Full Text] [PDF]

				D. Kobayashi, T. Nozawa, K. Imai, J.-i. Nezu, A. Tsuji, and I. Tamai Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 703 - 708. [Abstract] [Full Text] [PDF]

				M. Trauner and J. L. Boyer Bile Salt Transporters: Molecular Characterization, Function, and Regulation Physiol Rev, April 1, 2003; 83(2): 633 - 671. [Abstract] [Full Text] [PDF]

				B. Ugele, M. V. St-Pierre, M. Pihusch, A. Bahn, and P. Hantschmann Characterization and identification of steroid sulfate transporters of human placenta Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E390 - E398. [Abstract] [Full Text] [PDF]