AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 6 987-G991, Copyright © 1996 by American Physiological Society
Tumor necrosis factor-alpha stimulates adrenal glucocorticoid secretion in cholestatic rats
M. G. Swain and M. Maric
Liver Unit, University of Calgary, Alberta, Canada.
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 E2 (PGE2) production. These results indicate that TNF-alpha
has a direct stimulatory effect on adrenal corticosterone secretion in
cholestatic rats, possibly due to augmented adrenal PGE2 release.
