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Inhibition of folic acid transport in cultured human trophoblasts by progesterone
Author(s) -
Keating Elisa,
Lemos Clara,
Gonçalves Pedro,
Campos Isabel,
Costa Fernanda,
Azevedo Isabel,
Martel Fátima
Publication year - 2007
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.21.5.a533-b
Subject(s) - efflux , abcg2 , transporter , placenta , chemistry , receptor , in vivo , p glycoprotein , probenecid , biochemistry , biology , atp binding cassette transporter , pharmacology , multiple drug resistance , gene , fetus , pregnancy , genetics , microbiology and biotechnology , antibiotics
Cellular folic acid (FA) pools are controlled by FA uptake systems (Folate Receptor – FR alpha, and Reduced Folate Carrier – RFC1), and also by efflux transporters belonging to the ATP‐binding cassete (ABC) superfamily. MRP1‐5 (members of the Multidrug Resistance Protein family), BCRP (Breast Cancer Resistance Protein) and MDR1 (P‐glycoprotein) are some of these transporters which are expressed at the placental level. The aim of this work was to investigate the putative involvement of members of the ABC superfamily of transporters on FA cellular homeostasis in the human placenta. For this, the effect of selective inhibitors of MDR1, MRP and BCRP on 3 H‐FA uptake and efflux was investigated in BeWo cells and primary cultures of human cytotrophoblasts (CTB). Our results show that 3 H‐FA uptake and efflux in BeWo cells and in human cytotrophoblasts are not affected by verapamil, probenecid, or fumitremorgin C, suggesting that MDR1, MRP or BCRP, respectively, are not involved in FA homeostasis. However, progesterone was found to inhibit both uptake and efflux of 3 H‐FA, both in BeWo cells and in CTB. The characteristics of the progesterone effect lead us to the conclusion that it inhibits RFC1. It is suggested that progesterone, a sterol produced by the placenta, may inhibit FA placental uptake in vivo . This work was supported by FCT and Programa Ciência, Tecnologia e Inovação do Quadro Comunitário de Apoio (POCTI/SAU‐FCF/59382/2004).