Characterization of an organic anion-transporting polypeptide (OATPp-B) in human placenta

• Published in: The journal of clinical endocrinology and metabolism 2002-04, Vol.87 (4), p.1856-1863
• Main Authors: ST-PIERRE, M. V, HAGENBUCH, B, UGELE, B, MEIER, P. J, STALLMACH, T
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biological Transport - drug effects; Biological Transport - physiology; Cells, Cultured; Endocrinopathies; Estrone - analogs & derivatives; Estrone - antagonists & inhibitors; Estrone - pharmacokinetics; Female; Fundamental and applied biological sciences. Psychology; Giant Cells - physiology; Hormone metabolism and regulation; Humans; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oocytes - metabolism; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Organic Anion Transporters - physiology; Placenta - metabolism; Pregnancy; Pregnancy. Parturition. Lactation; Pregnenolone - pharmacology; RNA, Messenger - metabolism; Thyroid. Thyroid axis (diseases); Trophoblasts - metabolism; Vertebrates: reproduction
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.87.4.1856

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 [(3)H]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.