A study of influence of progesterone on activity of Glycoprotein-P in vitro

Background. Glycoprotein-P (Pgp, АВСВ1) is a transporter protein participating in pharmacokinetics of medical drugs, and also in development of resistance of tumor cells to chemotherapy.

Aim. To study the influence of progesterone on the activity of Pgp in vitro on a cell model of human small intestinal epithelium.

Materials and Methods. The work was conducted on Caco-2 cells. The activity of Pgp was evaluated by transport of fexofenadine in a special transwell-system. Concentration of fexofenadine was analyzed by HPLC method. The amount of Pgp was determined by EIA method. Four series of experiments were conducted: control – cells preincubated with clean transport medium without addition of any substances; influence of rifampicin on the activity and synthesis of Pgp in the concentration 10 µmol/l in preincubation for 3 days (induction control); influence of progesterone on the activity of Pgp in concentrations 1, 10 and 100 µmol/l in preincubation for 30 min; influence of progesterone on the activity and synthesis of Pgp in concentrations 1, 10 and 100 µmol/l in preincubation for 3 days.

Results. Progesterone in the concentrations 1 and 10 µM in incubation with cells within 30 minutes did not show any reliable influence on the activity of Pgp, however, in concentration 100 µM it reduced the activity of the transporter protein.

In incubation of Caco-2 cells with progesterone in concentrations 1, 10 and 100 µM within 3 days the activity of Pgp remained unchanged. Progesterone in concentration 100 µM in incubation within 3 days significantly increased synthesis of Pgp in enterocytes by 114.3% as compared to control, and in other used concentrations (1 and 10 µM) it produced no reliable effect.

Conclusion. In in vitro experiments on Caco-2 cells progesterone in concentration 100 µM produces a direct inhibiting effect on the activity of Pgp; however, in incubation within 3 days it increases synthesis of the transporter protein, which cancels out its inhibitory activity.