Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Multidrug resistance phosphoglycoprotein (MDR1/P-gp) and breast cancer resistance protein (BCRP) were first isolated in chemoresistant cancer cells and have since been found in a variety of normal tissue, including the placenta. The potential function of MDR1/P-gp and BCRP in the human placenta is to protect the fetus from maternally circulating endogenous steroids and hormones, therapeutic drugs and toxins. The objective of this study was to examine the role of maternal steroids in the regulation of MDR1/P-gp and BCRP in the human placenta. Trophoblast cells were isolated from term placenta tissues and immunohistochemistry, western blot analysis and transport studies were used to determine the effect of maternal steroids on MDR1/P-gp and BCRP regulation. Maternal steroids, present at high concentrations in maternal serum, did not have an effect on BCRP in human syncytiotrophoblast. Estrogen and progesterone did not alter MDR1/P-gp levels in human syncytiotrophoblast, but cortisol significantly decreased MDR1/P-gp levels.

Mother's milk provides multiple benefits to the offspring. However, xenobiotics transferred into breast milk may pose a risk to the nursing infant. The breast cancer resistance protein (BCRP) actively transports xenobiotics into breast milk. BCRP also transports nutrients, like riboflavin, and together with recently identified riboflavin transporters (RFT), may provide a mechanism for riboflavin secretion into breast milk. Expression of RFT in the mammary gland remained unknown. Our objective was to characterize Bcrp and Rft mRNA expression in the mammary gland of FVB/N mice, and investigate a strategy to decrease excretion of BCRP-transported xenobiotics into the milk using riboflavin intervention. Rft and Bcrp mRNA were upregulated in the mammary gland of lactating mice. An intravenous riboflavin administration significantly reduced the levels of BCRP-transported cimetidine in milk. This study demonstrates the use of riboflavin to exploit the function of mammary BCRP in order to reduce xenobiotic secretion into breast milk.

Mother's milk provides multiple benefits to the offspring. However, xenobiotics transferred into breast milk may pose a risk to the nursing infant. The breast cancer resistance protein (BCRP) actively transports xenobiotics into breast milk. BCRP also transports nutrients, like riboflavin, and together with recently identified riboflavin transporters (RFT), may provide a mechanism for riboflavin secretion into breast milk. Expression of RFT in the mammary gland remained unknown. Our objective was to characterize Bcrp and Rft mRNA expression in the mammary gland of FVB/N mice, and investigate a strategy to decrease excretion of BCRP-transported xenobiotics into the milk using riboflavin intervention. Rft and Bcrp mRNA were upregulated in the mammary gland of lactating mice. An intravenous riboflavin administration significantly reduced the levels of BCRP-transported cimetidine in milk. This study demonstrates the use of riboflavin to exploit the function of mammary BCRP in order to reduce xenobiotic secretion into breast milk.