This investigation addresses the interaction of insulin (INS) and
glucocorticoid (GC) signaling in the hepatic regulation of
tryptophan oxygenase (TO) enzyme activity in the rat. Male
Wistar rats (200-250 g b.w) received an injection of the different
doses of INS (10, 25, 50, 70 and 100 μg/200 g b.w., i.p.) and
were used for experiments 3 h and 18 h after INS administration.
This study shows that maximum of TO activity was found at dose
of 50 μg of INS with peak increases observed at 3 h and 18 h
after injection of INS, while INS had no effect on TO activity in
adrenalectomized rats. The analysis of INS effects on
glucocorticoid receptor-complex (GC/GR complex) stability shows
that complexes from INS-treated rats are less stable than those
from control animals. In addition, INS-stimulated stability of
glucocorticoid receptor (GR) protein was significantly increased
from the controls. Furthermore, the results show that GC/GR
complexes from INS-treated rats could be activated and
accumulated at higher rate in cell nuclei of control animals.
These data support the involvement of INS in modulation of GC
signaling pathway which mediates, in part, the activity of TO.
GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes
