TY - JOUR
T1 - Ethinyl estradiol cholestasis involves alterations in expression of liver sinusoidal transporters
AU - Simon, Francis R.
AU - Fortune, John
AU - Iwahashi, Mieko
AU - Gartung, Garsten
AU - Wolkoff, Allan
AU - Sutherland, Eileen
N1 - Copyright:
Copyright 2006 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - The mechanisms involved in ethinyl estradiol-induced cholestasis are controversial. Basal bile flow was reduced by ethinyl estradiol administration, with a half time (t1/2) of 12.5 ± 0.6 h. In contrast, initial taurocholate uptake was not significantly reduced until 3 days to 59% of control and to 13 and 10% of control at 5 and 7 days, respectively. The t1/2 was 4.3 ± 0.1 days. These physiological changes were correlated with measurement of protein mass and steady-state mRNA for Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase), Na+-dependent taurocholate transporter, organic anion transporters, and membrane lipid fluidity. Ethinyl estradiol significantly decreased Na+-K+-ATPase activity and membrane fluidity. However, neither Na+-K+-ATPase α-subunit nor β-subunit mass was altered by ethinyl estradiol administration. In contrast, protein content of the Na+-dependent taurocholate transporter was significantly reduced to 21% of control (P < 0.001) at 5 days. The Na+-dependent taurocholate transporter was identified in sinusoidal membrane fractions as a doublet with a molecular size estimated to be 51 and 56 kDa. Although both bands were reduced with ethinyl estradiol treatment, the 56-kDa band was decreased more rapidly and to a greater extent than the 51-kDa band. The estimated t1/2, of 4.8 ± 0.6 days for the doublet was similar to that for Na+-dependent taurocholate uptake. The organic anion transporter protein mass was similarly reduced with time of ethinyl estradiol administration to 21% of control (P < 0.01) at 5 days. Ethinyl estradiol also rapidly decreased the steady-state mRNA levels of Na+-dependent and organic anion transporters to -50% and 15% of control at 5 days, respectively. These studies indicate early generalized abnormalities of the sinusoidal membrane lipid fluidity, Na+-K+-ATPase activity, and bile acid transport protein content. sodium-potassium-activated adenosinetriphosphatase; sodium-dependent bile acid transporter;.
AB - The mechanisms involved in ethinyl estradiol-induced cholestasis are controversial. Basal bile flow was reduced by ethinyl estradiol administration, with a half time (t1/2) of 12.5 ± 0.6 h. In contrast, initial taurocholate uptake was not significantly reduced until 3 days to 59% of control and to 13 and 10% of control at 5 and 7 days, respectively. The t1/2 was 4.3 ± 0.1 days. These physiological changes were correlated with measurement of protein mass and steady-state mRNA for Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase), Na+-dependent taurocholate transporter, organic anion transporters, and membrane lipid fluidity. Ethinyl estradiol significantly decreased Na+-K+-ATPase activity and membrane fluidity. However, neither Na+-K+-ATPase α-subunit nor β-subunit mass was altered by ethinyl estradiol administration. In contrast, protein content of the Na+-dependent taurocholate transporter was significantly reduced to 21% of control (P < 0.001) at 5 days. The Na+-dependent taurocholate transporter was identified in sinusoidal membrane fractions as a doublet with a molecular size estimated to be 51 and 56 kDa. Although both bands were reduced with ethinyl estradiol treatment, the 56-kDa band was decreased more rapidly and to a greater extent than the 51-kDa band. The estimated t1/2, of 4.8 ± 0.6 days for the doublet was similar to that for Na+-dependent taurocholate uptake. The organic anion transporter protein mass was similarly reduced with time of ethinyl estradiol administration to 21% of control (P < 0.01) at 5 days. Ethinyl estradiol also rapidly decreased the steady-state mRNA levels of Na+-dependent and organic anion transporters to -50% and 15% of control at 5 days, respectively. These studies indicate early generalized abnormalities of the sinusoidal membrane lipid fluidity, Na+-K+-ATPase activity, and bile acid transport protein content. sodium-potassium-activated adenosinetriphosphatase; sodium-dependent bile acid transporter;.
KW - Bile acids
KW - Fluidity
KW - Organic anion transporter
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M3 - Article
AN - SCOPUS:33749290063
SN - 0002-9513
VL - 271
SP - G1039-G1042
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 6 PART 1
ER -