P-glycoprotein has negligible effects on estradiol and testosterone in mice.
P-glycoprotein (P-gp) is an important factor at the blood-brain barrier preventing passage of a wide variety of substances into the brain. Several studies have provided evidence that some drugs and certain steroid hormones are substrates or inhibitors of P-gp. However, the situation is unclear with regard to gonadal steroids, which have considerable central nervous effects. In vitro, experiments on the relationship between estradiol and P-gp are equivocal. We used abcb1ab knock-out mice and wild-type mice to determine the uptake of [3H]-17-beta-estradiol and [3H]-testosterone into the cerebrum and other organs after subcutaneous administration. The organ/plasma quotients showed no significant group effects. We concluded that P-gp does not influence the penetration of testosterone and estradiol to a biologically significant extent.
Ebinger
Martin
M
Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Behl
Christian
C
Rosenhagen
Marcus
M
Uhr
Manfred
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics*; D004958:Estradiol / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D013739:Testosterone / Q000378:metabolism* / Q000493:pharmacokinetics; D014316:Tritium; D014781:Viscera / Q000187:drug effects / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014316:Tritium; D013739:Testosterone; D004958:Estradiol