Cortisol is transported by the multidrug resistance gene product P-glycoprotein.
The physiology of the multidrug transporter P-glycoprotein (Pgp) is still poorly understood. We now show evidence that cell lines with a high expression of Pgp display a reduced accumulation of cortisol and an ATP-dependent outward transport of the hormone. Cortisol efflux from Pgp negative cells does not have such an active component. Further we show that the steroid hormones cortisol, testosterone, and progesterone cause an immediate, dose-dependent increase of daunorubicin accumulation in Pgp overexpressing cells. These effects are particularly apparent for the more lipophilic steroids. These results demonstrate that Pgp may function as a transporter for cortisol and suggest a physiological role of the protein in steroid handling by organs such as the adrenal.
van Kalken
C K
CK
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Broxterman
H J
HJ
Pinedo
H M
HM
Feller
N
N
Dekker
H
H
Lankelma
J
J
Giaccone
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D003350:Cortodoxone / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000493:pharmacokinetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013256:Steroids / Q000096:biosynthesis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D013256:Steroids; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D016572:Cyclosporine; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone