Merola B, Longobardi S, Colao A, Di Somma C, Ferone D, Di Rella F, Pivonello R, Covelli V, Annunziato L, Lombardi G
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
Neuroendocrinology. 1996 Nov;64(5):393-7. doi: 10.1159/000127142.
The aim of this study was to evaluate the effect of acute human corticotropin (ACTH)-releasing hormone (CRH) administration (100 micrograms, as i.v. bolus) on tumor necrosis factor-alpha (TNF alpha) levels in the inferior petrosal sinuses and in the peripheral blood of 7 patients with Cushing's disease subjected to diagnostic inferior petrosal sinus sampling. Blood samples for ACTH, beta-endorphin (beta-EPH) and TNF alpha were collected from inferior petrosal sinuses and periphery simultaneously. In addition, TNF alpha concentrations were measured after CRH administration (10 nmol/l, 100 nmol/l and 1 mumol/l) in culture medium from primary cultures obtained in 3 of 7 patients. At baseline, plasma ACTH and beta-EPH levels were significantly higher in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma than in the contralateral one and in the periphery (p < 0.001) whereas no significant difference was found as far as serum TNF alpha levels were concerned. CRH administration caused a significant increase of ACTH (p < 0.001), beta-EPH (p < 0.01) and TNF alpha (p < 0.01) levels greater in the ipsilateral inferior petrosal sinus than in the contralateral one and in the periphery. In addition, CRH increased ACTH, beta-EPH and TNF alpha levels in the culture medium of three ACTH-secreting tumors at the doses of 100 nmol/l and 1 mumol/l (greater than 300, 200 and 110% of baseline pretreatment incubation levels, respectively). These data suggest that CRH may increase TNF alpha concentrations in the inferior petrosal sinus ipsilateral to the ACTH-secreting adenoma and in the peripheral blood as well. In addition, it stimulated TNF alpha release both in vivo and in vitro. These findings suggest the possibility that an imbalanced intrapituitary TNF alpha production can be detected in ACTH-secreting adenomas.
本研究旨在评估急性静脉推注100微克人促肾上腺皮质激素（ACTH）释放激素（CRH）对7例库欣病患者在进行诊断性岩下窦采血时岩下窦及外周血中肿瘤坏死因子-α（TNFα）水平的影响。同时从岩下窦和外周采集血样检测ACTH、β-内啡肽（β-EPH）和TNFα。此外，对7例患者中的3例进行原代培养，在培养基中加入不同浓度的CRH（10 nmol/l、100 nmol/l和1 μmol/l）后测量TNFα浓度。基线时，分泌ACTH的腺瘤同侧岩下窦血浆ACTH和β-EPH水平显著高于对侧岩下窦及外周血（p < 0.001），而血清TNFα水平无显著差异。给予CRH后，同侧岩下窦ACTH（p < 0.001）、β-EPH（p < 0.01）和TNFα（p < 0.01）水平显著升高，升高幅度大于对侧岩下窦及外周血。此外，在100 nmol/l和1 μmol/l剂量下，CRH使3例分泌ACTH肿瘤的培养基中ACTH、β-EPH和TNFα水平升高（分别比预处理前基线孵育水平高300%、200%和110%以上）。这些数据表明，CRH可能会使分泌ACTH的腺瘤同侧岩下窦及外周血中TNFα浓度升高。此外，它在体内和体外均刺激TNFα释放。这些发现提示，在分泌ACTH的腺瘤中可能检测到垂体内部TNFα产生失衡。
