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Transport of Estrone Sulfate by Human Placental Plasma Membrane Vesicles
Author(s) -
Nanovskaya Tatiana,
Patrikeeva Svetlana,
Wang Xiaoming,
Wang Qingrong,
Ahmed Mahmoud S
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.935.4
Subject(s) - estrone sulfate , multidrug resistance associated protein 2 , transporter , efflux , chemistry , epithelial polarity , biochemistry , estrone , apical membrane , membrane transport protein , placenta , fetal membrane , vesicle , atp binding cassette transporter , membrane , biology , fetus , hormone , pregnancy , genetics , gene
It has been suggested that the activities of the apical membranes uptake transporters together with the basolateral membranes efflux transporters potentiate each other in their transfer of sulfate‐conjugated compounds from the maternal to the fetal circulation. However, the ubiquitous presence and activities of steroid sulfatases in human placenta renders it unlikely that this dual transport system could occur in vivo because of the rapid deconjugation of estrone sulfate to estrone. Therefore, the objective of this study is to determine the role of placental transporters and steroid sulfatases in the bio‐disposition of estrone sulfate (E 1 ‐S). Preparations of membrane vesicles from human placentas were used to determine the activities of efflux transporters in the presence of ATP and uptake transporters in the presence of glutathione and α‐ketoglutarate. The hydrolysis of E 1 ‐S by the tissues’ steroid sulfatases was inhibited by the addition of 100nM STX64. In addition, the metabolism and transplacental transfer of E 1 ‐S across human placenta was determined using the technique of dual perfusion of isolated lobule. Our data revealed that the efflux transporters P‐gp, BCRP, MRP2, MRP3 and MRP4 as well as the uptake transporters OATPs 1A2, 3A1, 4A1, and 5A1are expressed in the apical membranes. On the other hand, the efflux transporter MRP5 and the uptake transporter OAT4 are expressed on both the apical and basolateral membranes while the transporters MRP1 and OATP2B1 are expressed only on the basolateral membranes ( Figure 1). The activities of the apical membranes uptake transporters for the transfer of E 1 ‐S in the presence of glutathione and α‐ketoglutarate were 72 ± 23 and 85 ± 6 fmol/mg*min −1 , respectively while the activities for the basolateral membranes’ transporters were 41± 25 and 111± 29 fmol/mg*min −1 , respectively. The activities of efflux transporters localized on the apical membranes were 52 ± 3 fmol/mg*min −1 , and the basolateral 48 ± 22 fmol/mg*min −1 . Moreover, the distribution of E 1 ‐S and its metabolite estrone (E 1 ) following 2 hours of its perfusion was as follows: The maternal circuit contained 19 ± 2% of E 1 ‐S and 16 ± 1 % of E 1 ; placental lobule contained 9 ± 8% of E 1 ‐S and 52 ± 11% of E 1 ; and the fetal circuit contained 1 ± 0.2% of E 1 ‐S and 4 ± 1 % of E 1 . Taken together, the above data suggest that the uptake transporters localized on the apical side of syncytiotrophoblast transport E 1 ‐S to the placental tissue where they are rapidly hydrolyzed by steroid sulfatases to E 1 . This biotransformation is followed by the release of the formed E1 into both maternal and fetal circuits ( Figure 2). On the other hand, placental efflux transporters localized on both sides of the membranes have a minor role in biodistribition of E 1 ‐S due to its rapid biotransformation to E 1 . Support or Funding Information Supported by the NICHD U10‐HD47891 and NIDA DA030998 grants.