Thyroid hormone regulates the expression and function of P-glycoprotein in Caco-2 cells.

PURPOSE: In patients with thyroid disorders, abnormalities in the pharmacokinetics of various drugs including digoxin, a substrate of P-glycoprotein (Pgp) which plays a crucial role in drug absorption and disposition, have been reported. In this study, we examined the effect of 3,5,3'-L-triiodothyronine (T(3)) on the function and expression of Pgp using the human intestinal epithelial cell line Caco-2.

MATERIALS AND METHODS: The effect of T(3) on the expression of Pgp and MDR1 mRNA was assessed by Western blotting and competitive polymerase chain reaction, respectively. Digoxin uptake and transport by Pgp was assessed using Caco-2 cell monolayers.

RESULTS: The expression of MDR1 mRNA was increased by T(3) treatment in a concentration-dependent manner. Pgp expression was also increased by 100 nM T(3), whereas it decreased on depletion of T(3). The amount of [(3)H]digoxin accumulated in Caco-2 cell monolayers treated with T(3) was diminished significantly compared with that in control cells. In addition, the basal-to-apical transcellular transport of [(3)H]digoxin was accelerated by T(3) treatment.

CONCLUSIONS: These results indicate that T(3) regulates the expression and function of Pgp. It is possible that changes in Pgp expression alter the pharmacokinetics of Pgp substrates in patients with thyroid disorders.