Role of OAT4 in Uptake of Estriol Precursor 16α-Hydroxydehydroepiandrosterone Sulfate Into Human Placental Syncytiotrophoblasts From Fetus
| Autor: | Tetsuo Maruyama, Masatoshi Tomi, Hiromi Eguchi, Mayuko Ozaki, Tomohiro Tawara, Kei Higuchi, Emi Nakashima, Sachika Nishimura, Tomohiro Nishimura |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Organic anion transporter 1 Estrone Placenta Syncytiotrophoblasts Organic Anion Transporters Sodium-Independent Tritium Sulfobromophthalein chemistry.chemical_compound Endocrinology Fetus Pregnancy Internal medicine Cyclosporin a Cell Line Tumor Chlorocebus aethiops medicine Animals Humans Transport Vesicles reproductive and urinary physiology Radioisotopes biology Dehydroepiandrosterone Sulfate Estriol Cell Membrane Dehydroepiandrosterone Basal plasma membrane Trophoblasts Organic anion-transporting polypeptide medicine.anatomical_structure HEK293 Cells chemistry embryonic structures COS Cells biology.protein Female hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 156(7) |
| ISSN: | 1945-7170 |
| Popis: | Estriol biosynthesis in human placenta requires the uptake of a fetal liver-derived estriol precursor, 16α-hydroxydehydroepiandrosterone sulfate (16α-OH DHEAS), by placental syncytiotrophoblasts at their basal plasma membrane (BM), which faces the fetal circulation. The aim of this work is to identify the transporter(s) mediating 16α-OH DHEAS uptake at the fetal side of syncytiotrophoblasts by using human placental BM-enriched vesicles and to examine the contribution of the putative transporter to estriol synthesis at the cellular level, using choriocarcinoma JEG-3 cells. Organic anion transporter (OAT)-4 and organic anion transporting polypeptide 2B1 proteins were enriched in human placental BM vesicles compared with crude membrane fraction. Uptake of [3H]16α-OH DHEAS by BM vesicles was partially inhibited in the absence of sodium but was significantly increased in the absence of chloride and after preloading glutarate. Uptake of [3H]16α-OH DHEAS by BM vesicles was significantly inhibited by OAT4 substrates such as dehydroepiandrosterone sulfate, estrone-3-sulfate, and bromosulfophthalein but not by cyclosporin A, tetraethylammonium, p-aminohippuric acid, or cimetidine. These characteristics of vesicular [3H]16α-OH DHEAS uptake are in good agreement with those of human OAT4-transfected COS-7 cells as well as forskolin-differentiated JEG-3 cells. Estriol secretion from differentiated JEG-3 cells was detected when the cells were incubated with 16α-OH DHEAS for 8 hours but was inhibited in the presence of 50 μM bromosulfophthalein. Our results indicate that OAT4 at the BM of human placental syncytiotrophoblasts plays a predominant role in the uptake of 16α-OH DHEAS for placental estriol synthesis. |
| Databáze: | OpenAIRE |
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