Transepithelial transport and cellular accumulation of steroid hormones and polychlorobiphenyl in porcine kidney cells expressed with human P-glycoprotein.
Endocrine disrupters such as sex hormone-like chemicals and the non-physiological ligands for aryl hydrocarbon receptor (AhR) exert many adverse biological effects. The ligands for AhR disturb gene expression downstream of the gene induced by estrogen receptor at a very low concentration. Thus, transepithelial transport and cellular accumulation of cortisol (COR) and estrogen as congeners of sex hormone-like chemicals, and 3,3',4,4'-tetrachlorobiphenyl (TeCB) as one of the ligands for AhR were examined in a monolayer of porcine kidney cells transfected with human P-glycoprotein (LLC-COL). The net basal-to-apical transport of COR increased in LLC-COL compared to that in the wild type cells (LLC-PKI) the same as in vinblastine, whereas the net transport of estradiol (EST) was not detected in either cell group. Though the diffusion transports of EST for both directions, basal-to-apical and apical-to-basal, were higher than that of COR, cellular accumulation of EST was higher than that of COR. Transepithelial transport of TeCB was very low and the net basal-to-apical transport was not detected, while it was highly accumulated in the epithelial cells. The accumulation was slightly higher in LLC-COL than in LLC-PKI at high dose.
Fujise
Hiroshi
H
High-Tech Research Center, Institute of Biosciences, Azabu University, Sagamihara, Kanagawa, Japan. fujise@azabu-u.ac.jp
Annoura
Takeshi
T
Sasawatari
Shigemi
S
Ikeda
Teruo
T
Ueda
Kazumitsu
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D002462:Cell Membrane; D004703:Endocrine System / Q000187:drug effects; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D004958:Estradiol / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004785:Environmental Pollutants; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D006854:Hydrocortisone