F. Chantoux et al., COMPETITIVE-INHIBITION OF THYROID-HORMONE UPTAKE INTO CULTURED RAT-BRAIN ASTROCYTES BY BILIRUBIN AND BILIRUBIN CONJUGATES, Molecular and cellular endocrinology, 97(1-2), 1993, pp. 145-151
Thyroid hormone (TH) metabolism is altered in cases of unconjugated hy
perbilirubinemia. These effects might involve inhibition of TH uptake
by their target cells. Astrocytes, which are in close contact with the
membranes of brain capillaries, might be the first brain cells to com
e into contact with bilirubin. Cultured rat brain astrocytes were used
as a model to study the effects of bilirubin and bilirubin analogues
on TH uptake. The initial uptake of [I-125]T-3 and [I-125]T-4 was inhi
bited by unconjugated bilirubin, biliverdin, ditaurobilirubin and bili
rubin glucuronides. The inhibition: of T-3 uptake by the bilirubin ana
logues was competitive. The K-i values were: unconjugated bilirubin (3
1 mu M), biliverdin (48 mu M), ditaurobilirubin (2.5 mu M) and bilirub
in glucuronides (1.2 mu M). This Last value is similar to the K-m of T
-3 transport (0.4 mu M), indicating that bilirubin glucuronides have a
high affinity for the TH transport system. By contrast, the uptakes o
f [H-3]tryptophan and [H-3]glutamine were not inhibited. These results
suggest that the astrocyte plasma membrane bears specific bilirubin-i
nteraction sites that are closely related to the TH transport system.
However, uptake of [C-14]bilirubin by cultured astrocytes was a non-sa
turable process. Binding of bilirubin to the astrocyte plasma membrane
may inhibit the TH uptake and impair their metabolism and their actio
n on the intracellular targets.