Swain M G, Maric M
Liver Unit, University of Calgary, Alberta, Canada.
Am J Physiol. 1996 Jun;270(6 Pt 1):G987-91. doi: 10.1152/ajpgi.1996.270.6.G987.
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.
肿瘤坏死因子-α（TNF-α）能够激活下丘脑-垂体-肾上腺（HPA）轴。我们最近记录了内毒素和白细胞介素-1对胆汁淤积大鼠该轴激活的改变。因此，在本研究中，我们以假手术切除的大鼠作为对照，研究了TNF-α对胆管切除所致胆汁淤积大鼠HPA轴的激活作用。给胆管切除和假手术切除的大鼠体内注射TNF-α，两组动物的血浆促肾上腺皮质激素水平均有相似程度的升高，但胆汁淤积大鼠的皮质酮水平显著更高，这表明TNF-α对胆汁淤积大鼠有直接的类固醇生成作用。在进一步的实验中，通过证明TNF-α可诱导垂体切除的胆汁淤积大鼠而非对照大鼠分泌皮质酮，证实了这一推测。此外，仅在胆汁淤积大鼠中观察到TNF-α对体外肾上腺皮质酮分泌有直接刺激作用，可能是通过增加肾上腺前列腺素E2（PGE2）的产生。这些结果表明，TNF-α对胆汁淤积大鼠的肾上腺皮质酮分泌有直接刺激作用，可能是由于肾上腺PGE2释放增加所致。
