Chabre O, Liakos P, Vivier J, Chaffanjon P, Labat-Moleur F, Martinie M, Bottari S P, Bachelot I, Chambaz E M, Defaye G, Feige J J
Services d'Endocrinologie, Centre Hospitalier Universitaire, Grenoble, France. olivier
J Clin Endocrinol Metab. 1998 Sep;83(9):3134-43. doi: 10.1210/jcem.83.9.5140.
We studied a patient with food-induced, ACTH-independent, Cushing's syndrome and a unilateral adrenocortical adenoma. In vivo cortisol secretion was stimulated by mixed, glucidic, lipidic, or proteic meals. Plasma ACTH levels were undetectable, but iv injection of ACTH stimulated cortisol secretion. Unilateral adrenalectomy was followed by hypocortisolism with loss of steroidogenic responses to both food and ACTH. In vitro, cortisol secretion by isolated tumor cells was stimulated by the gut hormone gastric inhibitory polypeptide (GIP) and ACTH, but not by another gut hormone, glucagon-like peptide-1 (GLP-1). Both peptides stimulated the production of cAMP but not of inositol 1,4,5-trisphosphate. In quiescent cells, GIP and ACTH stimulated [3H]thymidine incorporation and p42-p44 mitogen-activated protein kinase activity. GIP receptor messenger ribonucleic acid (RNA), assessed by RT-PCR, was highly expressed in the tumor, whereas it was undetectable in the adjacent hypotrophic adrenal tissue, in two adrenal tumors responsible for food-independent Cushing's syndrome, and in two hyperplastic adrenals associated with ACTH hypersecretion. In situ hybridization demonstrated that expression of GIP receptor RNA was confined to the adrenocortical tumor cells. Low levels of ACTH receptor messenger RNA were also detectable in the tumor. We conclude that abnormal expression of the GIP receptor allows adrenocortical cells to respond to food intake with an increase in cAMP that may participate in the stimulation of both cortisol secretion and proliferation of the tumor cells.
我们研究了一名患有食物诱导的、促肾上腺皮质激素非依赖性库欣综合征及单侧肾上腺皮质腺瘤的患者。混合性、含碳水化合物、含脂质或含蛋白质的餐食均可刺激体内皮质醇分泌。血浆促肾上腺皮质激素水平检测不到，但静脉注射促肾上腺皮质激素可刺激皮质醇分泌。单侧肾上腺切除术后出现皮质醇减少症，同时丧失了对食物和促肾上腺皮质激素的类固醇生成反应。在体外，分离的肿瘤细胞的皮质醇分泌受到肠促胰液素胃抑制多肽（GIP）和促肾上腺皮质激素的刺激，但不受另一种肠促胰液素胰高血糖素样肽-1（GLP-1）的刺激。这两种肽均刺激环磷酸腺苷（cAMP）的产生，但不刺激肌醇1,4,5-三磷酸的产生。在静止细胞中，GIP和促肾上腺皮质激素刺激[3H]胸腺嘧啶掺入及p42-p44丝裂原活化蛋白激酶活性。通过逆转录聚合酶链反应（RT-PCR）评估，GIP受体信使核糖核酸（RNA）在肿瘤中高度表达，而在相邻的萎缩性肾上腺组织、两个导致非食物依赖性库欣综合征的肾上腺肿瘤以及两个与促肾上腺皮质激素分泌过多相关的增生性肾上腺中均检测不到。原位杂交显示GIP受体RNA的表达局限于肾上腺皮质肿瘤细胞。肿瘤中也可检测到低水平的促肾上腺皮质激素受体信使核糖核酸。我们得出结论，GIP受体的异常表达使肾上腺皮质细胞能够对食物摄入作出反应，导致cAMP增加，这可能参与刺激皮质醇分泌和肿瘤细胞增殖。
