Tumour necrosis factor-[alpha] stimulates adrenal glucocorticoid
secretion in cholestatic rats.
Swain, Mark G., and Mirjana Maric.
Liver Unit, GI Research Group, University of Calgary, Calgary,
Alberta, Canada, T2N 1N4
APStracts 2:0263G, 1995.
Tumour necrosis factor-[alpha] (TNF) 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-induced activation of the HPA axis in rats with
cholestasis due to bile duct resection, using sham resected rats as
controls. Administration of TNF to bile duct and sham resected rats
in vivo resulted in a similar increase in plasma ACTH levels in both
groups of animals, but significantly higher corticosterone levels in
cholestatic rats, suggesting a direct steroidogenic effect of TNF in
cholestatic rats. This suggestion was confirmed in further
experiments by the demonstration of TNF-induced corticosterone
secretion in hypophysectomized cholestatic, but not control, rats.
Furthermore, a direct stimulatory effect of TNF upon adrenal
corticosterone secretion in vitro was noted only for cholestatic
rats, possibly via augmented adrenal PGE2 production. These results
indicate that TNF has a direct stimulatory effect upon adrenal
corticosterone secretion in cholestatic rats, possibly due to
augmented adrenal PGE2 release.
Received 31 August 1995; accepted in final form 7 December 1995.
APS Manuscript Number G383-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95