Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta.
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.
St-Pierre
M V
MV
Department of Medicine, Institute of Clinical Pathology, University Hospital, CH-8091 Zurich, Switzerland. stpierre@kpt.unizh.ch
Hagenbuch
B
B
Ugele
B
B
Meier
P J
PJ
Stallmach
T
T
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004970:Estrone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D005260:Female; D015726:Giant Cells / Q000502:physiology; D006801:Humans; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011284:Pregnenolone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism
D027361:Organic Anion Transporters; D012333:RNA, Messenger; C450859:SLCO2B1 protein, human; C018370:pregnenolone sulfate; D004970:Estrone; D011284:Pregnenolone; C017296:estrone sulfate