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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2).

Progestins are widely used as oral contraceptives and hormone replacement therapy. Recently it has been demonstrated that many progestins are inhibitors of P-glycoprotein, possibly explaining gender differences in drug actions. In vitro evidence suggested that at least norgestimate might also inhibit other transporters like the multidrug resistance-associated protein 2 (MRP2). We therefore investigated whether norgestimate, desogestrel, medroxyprogesterone acetate, norethisterone, progesterone, cyproterone acetate, chlormadinone acetate, and levonorgestrel inhibit MRP2 in vitro using confocal laser scanning microscopy and 5-chloromethylfluorescein diacetate as a prodrug of the fluorescent 5-chloromethylfluorescein (CMF), which is actively transported by MRP2 as glutathione conjugate. Of the progestins tested, only norgestimate (50 microM) and progesterone (100 microM) significantly increased intracellular CMF fluorescence by 62% and 53%, respectively. In conclusion, the progestins norgestimate and progesterone significantly inhibit the transport activity of MRP2 in vitro.[1]


  1. Interaction of progestins with the human multidrug resistance-associated protein 2 (MRP2). Lindenmaier, H., Becker, M., Haefeli, W.E., Weiss, J. Drug Metab. Dispos. (2005) [Pubmed]
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