Is testosterone a substrate of P-glycoprotein in abcb1ab knock out mice?

P-glycoprotein (P-gp) is an important factor at the blood brain barrier preventing the penetration of a wide variety of substances into the brain. P-gp is a drug transport protein, located in the apical membrane of endothelial cells. Utilizing ATP hydrolysis as an energy source, it exports molecules which attempt to pass through the cell membrane from the outside to the inside, protecting cells from toxins and a wide range of substances. Several studies have provided evidence that certain steroid hormones are substrates or inhibitors of P-gp. As reported elsewhere, testosterone seems to be an inhibitor, but it is unclear whether or not testosterone is also a substrate of P-gp. Considering the tremendous effects testosterone exerts on cognitive, emotional, behavioral and developmental functions we tried to answer this question. abcb1ab knock out mice were used to determine the uptake of [3H]-testosterone into plasma, brain, and other organs. 2h after s.c. injection of 1.7 ng [3H]-testosterone/g bodyweight, the mice were deeply anaesthetized and decapitated. Radioactivity in plasma and organs was measured in a beta-counter. Testosterone levels were higher in the brains of abcb1ab -/- than in wild type controls, providing evidence that testosterone might be a weak substrate of P-gp. However, the effects were only small.