Document Detail


Functional differences in steroid sulfate uptake of organic anion transporter 4 (OAT4) and organic anion transporting polypeptide 2B1 (OATP2B1) in human placenta.
MedLine Citation:
PMID:  18501590     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human trophoblasts depend on the supply of external precursors such as dehydroepiandrosterone-3-sulfate (DHEA-S) and 16alpha-OH-DHEA-S for synthesis of estrogens. Recently, we have characterized the uptake of DHEA-S by isolated mononucleated trophoblasts and identified different transporter polypeptides involved in this process. Immunohistochemistry of 1st and 3rd trimester placenta detected organic anion transporter 4 (OAT4) and organic anion transporting polypeptide 2B1 (OATP2B1, former name OATP-B) in cytotrophoblast membranes and at the basal surface of the syncytiotrophoblast, indicating that both transporter polypeptides are involved in placental uptake of foetal derived steroid sulfates. In the present study we have characterized and compared the kinetics of DHEA-S and estrone sulfate (E(1)S) uptake by these transporters stably expressed in FlpIn -HEK293 cells using the Flp recombinase-mediated site-specific recombination. Uptake of E(1)S by OAT4- and OATP2B1-transfected cells was highly increased compared to the non-transfected cells. In contrast, DHEA-S uptake was only highly increased in OAT4 (40 times), but only weakly enhanced in OATP2B1 cells. The uptake of DHEA-S and E(1)S by OAT4 was partly Na(+)-dependent (about 50%), whereas uptake of DHEA-S by OATP2B1 was Na(+)-independent. Kinetic analysis of the initial uptake rates of E(1)S by OAT4 and OATP2B1 gave very similar values for K(m) (about 20microM) and V(max) (about 600pmol/(minxmg protein)). In contrast, the affinity of DHEA-S towards OATP2B1 was about 10 times lower (K(m)>200microM) then for OAT4 (K(m)=29microM). Our results suggest different physiological roles of the two transporter polypeptides in placental uptake of foetal derived steroid sulfates. OATP2B1 seems not to be involved in de novo synthesis of placental estrogens but may contribute to the clearance of estrogen sulfates from foetal circulation.
Authors:
Bernhard Ugele; Andrew Bahn; Monika Rex-Haffner
Publication Detail:
Type:  Journal Article     Date:  2008-04-11
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  111     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-08-01     Completed Date:  2008-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Affiliation:
Klinikum der Universität München, Lindwurmstr. 2a, D-80337 München, Germany. Bernhard.Ugele@med.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Cell Line
Dehydroepiandrosterone Sulfate / pharmacokinetics
Estrone / analogs & derivatives,  pharmacokinetics
Female
Humans
Kidney / cytology
Models, Biological
Organic Anion Transporters / genetics*,  metabolism*
Organic Anion Transporters, Sodium-Independent / genetics*,  metabolism*
Placenta / metabolism*
Transfection
Tritium
Trophoblasts / metabolism
Chemical
Reg. No./Substance:
0/Organic Anion Transporters; 0/Organic Anion Transporters, Sodium-Independent; 0/SLC22A9 protein, human; 0/SLCO2B1 protein, human; 10028-17-8/Tritium; 481-97-0/estrone sulfate; 53-16-7/Estrone; 651-48-9/Dehydroepiandrosterone Sulfate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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