Tumor necrosis factor-alpha stimulates adrenal glucocorticoid secretion in cholestatic rats.
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.
Swain
M G
MG
Liver Unit, University of Calgary, Alberta, Canada.
Maric
M
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002779:Cholestasis / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D003345:Corticosterone