The effects of female sex hormones estradiol and progesterone on P-glycoprotein (Pgp) functioning have been investigated using Caco-2 cells. Pgp activity was analyzed in a transwell system by the transport of its substrate, fexofenadine. The amount of the transporter protein was analyzed by enzyme immunoassay. Incubation of Caco-2 cells with 10 μM estradiol and incubation for 3 days increased activity and synthesis of Pgp. Moreover, this effect was suppressed by the inhibitor of the constitutive androstane receptor (CAR) CINPA 1. Incubation of these cells with 100 μM progesterone for 3 days increased Pgp synthesis, but its activity remained unchanged due to non-genomic (direct) inhibition of Pgp molecule by gestagen. The pregnan-X receptor inhibitor (PXR), ketoconazole suppressed the inducing effect of progesterone on Pgp synthesis. The combination of 10 μM estradiol and 100 μM progesterone increased Pgp synthesis, but did not increase the transporter protein activity, due to direct inhibition of the Pgp molecule by progestogen. Thus, it was found that estradiol increased activity and synthesis of Pgp by stimulating CAR, and progesterone stimulated transporter protein synthesis by activating PXR.
Shchulkin A.V. et al. Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro // Biomeditsinskaya khimiya. - 2020. - V. 66. -N 6. - P. 444-449.
Shchulkin A.V. et al., "Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro." Biomeditsinskaya khimiya 66.6 (2020): 444-449.
Shchulkin, A. V., Chernykh, I. V., Popova, N. M., Slepnev, A. A., Yakusheva, E. N. (2020). Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro. Biomeditsinskaya khimiya, 66(6), 444-449.