In vivo response to growth hormone-releasing peptide-6 in adrenocorticotropin-dependent Cushing鈥檚 syndrome by lung carcinoid tumor is associated with growth hormone secretagogue receptor type 1a mRNA expression

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• 作者：M. C. Machado ; S. V. S谩 ; T. S. Goldbaum…
• 关键词：GHS ; GHRP ; 6 ; GHSR ; 1a ; ACTH ; dependent Cushing鈥檚 syndrome ; carcinoid tumor
• 刊名：Journal of Endocrinological Investigation
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：30
• 期：4
• 页码：334-340
• 全文大小：
• 参考文献：1.Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing鈥檚 syndrome. N Engl J Med 1991, 325: 897鈥?05.PubMed CrossRef
  2.Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing鈥檚 syndrome and pseudo-Cushing鈥檚 states. Endocr Rev 1998, 19: 647鈥?2.PubMed
  3.Invitti C, Pecori Giraldi F, de Martin M, Cavagnini F. Diagnosis and management of Cushing鈥檚 syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 1999, 84: 440鈥?.PubMed
  4.Kaltsas GA, Giannulis MG, Newell-Price JD, et al. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing鈥檚 disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1999, 84: 487鈥?2.PubMed
  5.Colao A, Faggiano A, Pivonello R, et al.; Study Group of the Italian Endocrinology Society on the Pathophsiology of the Hypothalamic-Pituitary-Adrenal Axis. Inferior petrosal sinus sampling in the differential diagnosis of Cushing鈥檚 syndrome: results of an Italian multicenter study. Eur J Endocrinol 2001, 144: 499鈥?07.PubMed CrossRef
  6.Lefournier V, Martinie M, Vasdev A, et al. Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing鈥檚 disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage. J Clin Endocrinol Metab 2003, 88: 196鈥?03.PubMed CrossRef
  7.Ghigo E, Arvat E, Ramunni J, et al. Adrenocorticotropin- and cortisol-releasing effect of hexarelin, a synthetic growth hormone-releasing peptide, in normal subjects and patients with Cushing鈥檚 syndrome. J Clin Endocrinol Metab 1997, 82: 2439鈥?4.PubMed
  8.Arvat E, Giordano R, Ramunni J, et al. Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing鈥檚 disease bearing a pituitary microadenoma, but not in those with macroadenoma. J Clin Endocrinol Metab 1998, 83: 4207鈥?1.PubMed
  9.Grottoli S, Arvat E, Gauna C, et al. Effects of alprazolam, a benzodiazepine, on the ACTH-, GH- and PRL-releasing activity of hexarelin, a synthetic peptidyl GH secretagogue (GHS), in patients with simple obesity and in patients with Cushing鈥檚 disease. Pituitary 1999, 2: 197鈥?04.PubMed CrossRef
  10.Arvat E, Ramunni J, Giordano R, et al. Effects of the combined administration of hexarelin, a synthetic peptidyl GH secretagogue, and hCRH on ACTH, cortisol and GH secretion in patients with Cushing鈥檚 disease. J Endocrinol Invest 1999, 22: 23鈥?.PubMed CrossRef
  11.Leal-Cerro A, Torres E, Soto A, et al. Ghrelin is no longer able to stimulate growth hormone secretion in patients with Cushing鈥檚 syndrome but instead induces exaggerated corticotropin and cortisol responses. Neuroendocrinology 2002, 76: 390鈥?.PubMed CrossRef
  12.Oliveira JH, Vieira JG, Abucham J, Lengyel AM. GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing鈥檚 disease: comparison with DDAVP. J Endocrinol Invest 2003, 26: 230鈥?.PubMed CrossRef
  13.Arnaldi G, Mancini T, Kola B, et al. Cyclical Cushing鈥檚 syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. J Clin Endocrinol Metab 2003, 88: 5834鈥?0.PubMed CrossRef
  14.Pfaffl MW. A new mathematical model for relative quantification in real time RT-PCR. Nucleic Acids Research 2001, 29: e45.PubMed Central PubMed CrossRef
  15.Gnanapavan S, Kola B, Bustin SA, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002, 87: 2988.PubMed CrossRef
  16.de Keyzer Y, Lenne F, Bertagna X. Widespread transcription of the growth hormone-releasing peptide receptor gene in neuroendocrine human tumors. Eur J Endocrinol 1997, 137: 715鈥?.PubMed CrossRef
  17.Korbonits M, Bustin SA, Kojima M, et al. The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab 2001, 86: 881鈥?.PubMed
  18.Barlier A, Zamora AJ, Grino M, et al. Expression of functional growth hormone secretagogue receptors in human pituitary adenomas: polymerase chain reaction, triple in-situ hybridization and cell culture studies. J Neuroendocrinol 1999, 11: 491鈥?02.PubMed CrossRef
  19.Lania A, Ballare E, Corbetta S, Filopanti M, Persani L, Spada A. Growth hormone-releasing hexapeptide (GHRP-6) increases intracellular calcium concentrations in cultured cells from human pituitary adenomas of different types. Eur J Endocrinol 1998, 139: 343鈥?.PubMed CrossRef
  20.Ghe C, Cassoni P, Catapano F, et al. The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells. Endocrinology 2002, 143: 484鈥?1.PubMed CrossRef
  21.Tamura H, Kamegai J, Sugihara H, Kineman RD, Frohman LA, Wakabayashi I. Glucocorticoids regulate pituitary growth hormone secretagogue receptor gene expression. J Neuroendocrinol 2000, 12: 481鈥?.PubMed CrossRef
  22.Petersenn S, Rasch AC, Penshorn M, Beil FU, Schulte HM. Genomic structure and transcriptional regulation of the human growth hormone secretagogue receptor. Endocrinology 2001, 142: 2649鈥?9.PubMed
  
• 作者单位：M. C. Machado (1)
  S. V. S谩 (2)
  T. S. Goldbaum (1)
  M. Catania (1)
  V. C. Campos (3)
  M. L. C. Corr锚a-Giannella (2)
  D. Giannella-Neto (2)
  L. R. Salgado MD (1)
  
  1. Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo School of Medicine, Av. Dr. E. de Carvalho Aguiar 155, 8th floor, Cerqueira Cesar, 05403-060, Sao Paulo, SP, Brazil
  2. Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of Sao Paulo School of Medicine, Sao Paulo, SP
  3. Division of Endocrinology and Metabolism, University of Sergipe School of Medicine, Aracaju, SE, Brazil
  
• 刊物类别：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 刊物主题：Medicine/Public Health, general; Endocrinology; Metabolic Diseases;
• 出版者：Springer International Publishing
• ISSN：1720-8386

文摘

GH secretagogues (GHS) have been used for the differential diagnosis of ACTH-dependent Cushing鈥檚 syndrome (CS) since 1997 due to their ability to increase ACTH and cortisol levels in Cushing鈥檚 disease. The aim of this study was to correlate ACTH response to GH-releasing peptide-6 (GHRP-6) in vivo with GH secretagogue receptor type 1a (GHSR-1a) mRNA expression in a patient with lung carcinoid tumor. The patient was a 26-yr-old male with diagnosis of ACTH-dependent CS. He presented negative responses to human CRH and desmopressin tests; yet, a significant increase in ACTH after the GHRP-6 test was observed. Sellar magnetic resonance imaging (MRI) showed slight posterior hypointensity, but bilateral petrosal sinus sampling did not show central gradient. Computed tomography (CT) and MRI of thorax/abdomen/cervical were negative and 111In-pentetreotide scintigraphy depicted abnormal uptake on the right lung. The patient was submitted to right thoracotomy for exeresis of lung nodule and hilar lymph node which were characterized as atypical lung carcinoid tumor and he presented clinical and laboratorial remission after surgery. GHSR-1 a mRNA expression was studied with real-time quantitative PCR and tumor data were compared with fragments of normal lung and pituitary. There was a higher GHSR-1 a expression in the lung carcinoid tumor as compared with normal tissues. The ACTH response to GHRP-6 in a patient with ectopic ACTH production by a lung carcinoid tumor was associated with GHSR-1a expression in the tumor tissue, suggesting an association between GHSR-1a mRNA overexpression and the in vivo response to GHS. Key-words GHS GHRP-6 GHSR-1a ACTH-dependent Cushing鈥檚 syndrome carcinoid tumor