| Title | Estradiol and Progesterone-Mediated Regulation of P-gp in P-gp over-expressing cells (NCI-ADR-RES) and Placental cells (JAR). | | Author(s) | Coles LD, Lee IJ, Voulalas PJ, Eddington ND | | Source | Mol Pharm 2009 Oct 8. | | Abstract | Purpose. The effect of progesterone and estrogen treatment on the expression and function of P-glycoprotein (P-gp) was evaluated in JAR cells and a P-gp over-expressing cell line, NCI-ADR-RES. Materials and Methods. Western blot analysis and real-time Q-PCR were used to evaluate P-gp protein and MDR1 mRNA expression respectively in the cells following incubation with progesterone (P4) and/or beta-estradiol (E2). Cellular uptake studies of the P-gp substrates, saquinavir and taxol, were performed to evaluate function.
Results. Treatment with either E2 or P4 resulted in a significant increase in P-gp protein levels in the NCI-ADR-RES cells at concentrations of or greater than 100 nM or 10 nM, respectively. JAR cells also had increased levels of P-gp with 100 nM of P4 but were much more sensitive to E2 showing increased P-gp at a concentration of 1 nM. Furthermore, E2 or P4 treatment resulted in a significant decrease in cellular uptake of the P-gp substrates tested in these cells lines. Based on mRNA quantitation, a transient increase (2-fold) in MDR1 levels was observed at 8 hr post-incubation with either E2 or P4, while MDR1 levels remained high in the JAR cells treated with E2 for 72 hr post-incubation. The addition of actinomycin D, a transcription inhibitor negated the increase in P-gp by P4 and E2.
Conclusion. These hormones P4 or E2 increase P-gp expression and function in NCI-ADR-RES and JAR cells with the ERalpha-expressing cells (JAR) much more sensitive to E2. Furthermore, transcriptional regulation by E2 and P4 likely contributes to the modulation of P-gp levels. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19813763 |
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