Activity Inhibition of Progesterone on OCTN2 and its Effect on L-Carnitine Renal Excretion

OBJECTIVE To investigate the effect of progesterone on the activity of carnitine/organic cation transporter 2(OCTN2), and explore whether progesterone can reduce plasma L-carnitine concentration during pregnancy by inhibiting the renal OCTN2 activity and changing the renal excretion of L-carnitine. METHODS Used the established MDCK-hOCTN2 cell model with stable and high expression of human OCTN2, the inhibitory effect of progesterone on OCTN2 was investigated with mildronate and d₃-L-carnitine as substrates. Normal female ICR mice were subcutaneously injected with progesterone to make their serum progesterone concentration reach the third trimester of pregnancy, then the urinary excretion of L-carnitine and L-carnitine concentrations in plasma and tissues were determined and compared with the control group. RESULTS Progesterone reduced the accumulation of mildronate or d₃-L-carnitine in MDCK-hOCTN2 cells in a concentration-dependent manner, and the IC₅₀ values were 8.7 μmol·L^-1and 14.0 μmol·L^-1, respectively. The serum concentrations of progesterone were 462-1 153 nmol·L^-1in the treated mice, which were equivalent to the physiological concentrations in late pregnancy. Compared with the control group, there were no significant differences in the urinary excretion of L-carnitine and L-carnitine levels in plasma, liver, kidney and heart of mice in the progesterone treated group. CONCLUSION Progesterone significantly inhibites the activity of OCTN2 in vitro, however, progesterone at levels observed in late pregnancy do not affect L-carnitine renal excretion and homeostasis.