Comparative analysis of tryptophan oxygenase activity and glucocorticoid receptor under the influence of insulin

Abstract

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.

An Emerging Cross-Species Marker for Organismal Health: Tryptophan-Kynurenine Pathway

“…It is generally accepted that GCs increase the expression and activity of hepatic TDO in rats and mice [ 29 , 70 , 71 , 72 , 73 ]. GC signaling involves de novo synthesis of TDO at the transcriptional level, which is mediated by GC-responsive elements on the promoter region of TDO [ 72 , 73 ].…”