Tumor necrosis factor-alpha stimulates adrenal glucocorticoid secretion in cholestatic rats
Swain, M.G.; Maric, M.
American Journal of Physiology 270(6 Pt 1): G987-G991
1996
ISSN/ISBN: 0002-9513 PMID: 8764206 Document Number: 455385
Tumor necrosis factor-alpha (TNF-alpha) is capable of activating the hypothalamic-pituitary-adrenal (HPA) axis. We have recently documented altered activation of this axis by endotoxin and interleukin-1 in cholestatic rats. Therefore, in this study, we examined TNF-alpha-induced activation of the HPA axis, in rats with cholestasis due to bile duct resection, with the use of sham-resected rats as controls. Administration of TNF-alpha to bile duct- and sham-resected rats in vivo resulted in a similar increase in plasma adrenocorticotropic hormone levels in both groups of animals but significantly higher corticosterone levels in cholestatic rats, suggesting a direct steroidogenic effect of TNF-alpha in cholestatic rats. This suggestion was confirmed in further experiments by the demonstration of TNF-alpha-induced corticosterone secretion in hypophysectomized cholestatic but not control rats. Furthermore, a direct stimulatory effect of TNF-alpha on adrenal corticosterone secretion in vitro was noted only for cholestatic rats, possibly via augmented adrenal prostaglandin E-2 (PGE-2) production. These results indicate that TNF-alpha has a direct stimulatory effect on adrenal corticosterone secretion in cholestatic rats, possibly due to augmented adrenal PGE-2 release.