生长激素释放激素受体与肾上腺肿瘤关系的初步研究_《华西医学》

作者：

袁高品 , 张亭 ,  安振梅

四川大学华西医院内分泌科（成都，610041）;

关键词：

肾上腺肿瘤生长激素释放激素受体生长激素释放激素免疫组织化学

DOI：

10.7507/1002-0179.20130061

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的　初步探讨生长激素释放激素受体（GHRHR）在肾上腺肿瘤组织中的表达及其在临床中的实际应用价值。方法　应用免疫组织化学方法检测2001年1月－2009年10月间187例肾上腺肿瘤和20例正常肾上腺组织标本中GHRHR的表达。结果　肾上腺皮质肿瘤与肾上腺髓质肿瘤、正常肾上腺组织比较，GHRHR表达明显增高（阳性率分别为99%、45%、55%），GHRHR在肾上腺皮质醇瘤和醛固酮瘤中表达的差异有统计学意义，在肾上腺皮质腺瘤、皮质腺癌、皮质增生中表达的差异有统计学意义。结论　GHRHR在人正常肾上腺及肾上腺肿瘤组织中的表达，为在垂体外组织及人类肿瘤组织存在GHRHR的表达提供了直接证据；GHRHR可能会用于肾上腺皮质肿瘤和髓质肿瘤的鉴别诊断，但GHRHR尚不能用于良性和恶性肾上腺皮质肿瘤的鉴别诊断。GHRHR在肾上腺皮质相关肿瘤的高表达，可能与肾上腺皮质肿瘤的发病机制有关。

引用本文： 袁高品,张亭,安振梅. 生长激素释放激素受体与肾上腺肿瘤关系的初步研究. 华西医学, 2013, 28(2): 187-191. doi: 10.7507/1002-0179.20130061 复制

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4.	Matsubara S, Sato M, Mizobuchi M, et al. Differential gene expression of growth (GH) hormone-releasing hormone (GRH) and GRH receptor in various rat tissues[J]. Endocrinology, 1995, 136(9): 4147-4150.
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7.	Ziegler CG, Brown JW, Schally AV, et al. Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: antiproliferative effects of peptide analogues[J]. PNAS, 2009, 106(37): 15879-15884.
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10.	Chabre O, Liakos P, Vivier J, et al. Cushing’s syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis[J]. Clin Endocrinol Metab, 1998, 83(9): 3134-3143.
11.	Lacroix A, Bourdeau I, Lampron A, et al. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction[J]. Clin Endocrinol, 2010, 73(1): 1-15.
12.	Ye P, Mariniello B, Mantero F, et al. G-protein-coupled receptors in aldosterone-producing adenomas： a potential cause of hyperaldosteronism[J]. J Endocrinol, 2007, 195(1): 39-48.
13.	Mazzuco TL, Chabre O, Feige JJ, et al. Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis[J]. Mol Cell Endocrinol, 2007(265-266): 23-28.
14.	Mazzuco TL, Chabre O, Feige JJ, et al. Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and cushing’s syndrome features[J]. J Clin Endocrinol Metab, 2006, 91(1): 196-203.
15.	Lacroix A, N’Diaye N, Mircescu H, et al. The diversity of abnormal hormone receptors in adrenal Cushing’s syndrome allows novel pharmacological therapies[J]. Braz J Med Biol Res, 2000, 33(10): 1201-1209.
16.	Assie G, Louiset E, Sturm N, et al. Systematic analysis of G protein-coupled receptor gene expression in adrenocorticotropin-independent macronodular adrenocortical hyperplasia identifies novel targets for pharmacological control of adrenal cushing’s syndrome[J]. J Clin Endocrinol Metab, 2010, 95(10): E253-E262.
17.	Cartier D, Lihrmann I, Parmentier F, et al. Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome[J]. J Clin Endocrinol Metab, 2003, 88(1): 248-254.
18.	Louiset E, Contesse V, Groussin L, et al. Expression of serotonin7 receptor and coupling of ectopic receptors to protein kinase A and ionic currents in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cushing’s syndrome[J]. J Clin Endocrinol Metab, 2006, 91(11): 4578-4586.
19.	Louiset E, Isvi K, Gasc JM, et al. Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol[J]. Endocr Relat Cancer, 2008, 15(4): 1025-1034.
20.	Giuliani L, Lenzini L, Antonello M, et al. Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel insights for the pathophysiology of primary aldosteronism[J]. J Clin Endocrinol Metab, 2009, 94(2): 684-690.
21.	Barabutis N, Tsellou E, Schally AV, et al. Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor[J]. PNAS, 2007, 104 (13): 5575-5579.
22.	Kiaris H, Chatzistamou I, Schally AV, et al. Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor[J]. Proc Natl Acad Sci USA, 2003, 100(16): 9512-9517.
23.	Freddi S, Arnaldi G, Fazioli F, et al. Expression of growth hormone releasing hormone receptor splicing variants in human primary adrenocortical tumours[J]. Clin Endocrinol, 2005, 62(5): 533-538.

1. 　Li S, Huang S, Peng SB. Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression[J]. Int J Oncol, 2005, 27(5): 1329-1339.
2. 　Schally AV, Varga JL, Engel JB, et al. Antagonists of growth hormone releasing hormone: an emerging new therapy for cancer[J]. Nat Clin Pract Endocrinol Metab, 2008, 4(1): 33-43.
3. 　Havt A, Schally AV, Halmos G, et al. The expression of the pituitary growth hormone-releasing hormone receptor and its splice variants in normal and neoplastic human tissues[J]. PNAS, 2005, 102 (48): 17424-17429.
4. 　Matsubara S, Sato M, Mizobuchi M, et al. Differential gene expression of growth (GH) hormone-releasing hormone (GRH) and GRH receptor in various rat tissues[J]. Endocrinology, 1995, 136(9): 4147-4150.
5. 　Morel G, Gallego R, Boulanger L, et al. Restricted presence of the growth hormone releasing hormone receptor to somatotropes in rat and human pituitaries[J]. Neuroendocrinology, 1999, 70(2): 128-136.
6. 　Gallego R, Pintos E, García-Caballero T, et al. Cellular distribution of growth hormone-releasing hormone receptor in human reproductive system and breast and prostate cancers[J]. Histol Histopathoi, 2005, 20(3): 697-706.
7. 　Ziegler CG, Brown JW, Schally AV, et al. Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: antiproliferative effects of peptide analogues[J]. PNAS, 2009, 106(37): 15879-15884.
8. 　Schulz S, Röcken C, Schulz S. Immunocytochemical localisation of plasma membrane GHRH receptors in human tumours using a novel anti-peptide antibody[J]. Eur J Cancer, 2006, 42 (14): 2390-2396.
9. 　Lacroix A, Ndiaye N, Tremblay J, et al. Ectopical and abnormal hormone receptors in adrenal Cushing’s syndrome[J]. Endocr Rev, 22(1): 75-110.
10. 　Chabre O, Liakos P, Vivier J, et al. Cushing’s syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis[J]. Clin Endocrinol Metab, 1998, 83(9): 3134-3143.
11. 　Lacroix A, Bourdeau I, Lampron A, et al. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction[J]. Clin Endocrinol, 2010, 73(1): 1-15.
12. 　Ye P, Mariniello B, Mantero F, et al. G-protein-coupled receptors in aldosterone-producing adenomas： a potential cause of hyperaldosteronism[J]. J Endocrinol, 2007, 195(1): 39-48.
13. 　Mazzuco TL, Chabre O, Feige JJ, et al. Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis[J]. Mol Cell Endocrinol, 2007(265-266): 23-28.
14. 　Mazzuco TL, Chabre O, Feige JJ, et al. Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and cushing’s syndrome features[J]. J Clin Endocrinol Metab, 2006, 91(1): 196-203.
15. 　Lacroix A, N’Diaye N, Mircescu H, et al. The diversity of abnormal hormone receptors in adrenal Cushing’s syndrome allows novel pharmacological therapies[J]. Braz J Med Biol Res, 2000, 33(10): 1201-1209.
16. 　Assie G, Louiset E, Sturm N, et al. Systematic analysis of G protein-coupled receptor gene expression in adrenocorticotropin-independent macronodular adrenocortical hyperplasia identifies novel targets for pharmacological control of adrenal cushing’s syndrome[J]. J Clin Endocrinol Metab, 2010, 95(10): E253-E262.
17. 　Cartier D, Lihrmann I, Parmentier F, et al. Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome[J]. J Clin Endocrinol Metab, 2003, 88(1): 248-254.
18. 　Louiset E, Contesse V, Groussin L, et al. Expression of serotonin7 receptor and coupling of ectopic receptors to protein kinase A and ionic currents in adrenocorticotropin-independent macronodular adrenal hyperplasia causing Cushing’s syndrome[J]. J Clin Endocrinol Metab, 2006, 91(11): 4578-4586.
19. 　Louiset E, Isvi K, Gasc JM, et al. Ectopic expression of serotonin7 receptors in an adrenocortical carcinoma co-secreting renin and cortisol[J]. Endocr Relat Cancer, 2008, 15(4): 1025-1034.
20. 　Giuliani L, Lenzini L, Antonello M, et al. Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel insights for the pathophysiology of primary aldosteronism[J]. J Clin Endocrinol Metab, 2009, 94(2): 684-690.
21. 　Barabutis N, Tsellou E, Schally AV, et al. Stimulation of proliferation of MCF-7 breast cancer cells by a transfected splice variant of growth hormone-releasing hormone receptor[J]. PNAS, 2007, 104 (13): 5575-5579.
22. 　Kiaris H, Chatzistamou I, Schally AV, et al. Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor[J]. Proc Natl Acad Sci USA, 2003, 100(16): 9512-9517.
23. 　Freddi S, Arnaldi G, Fazioli F, et al. Expression of growth hormone releasing hormone receptor splicing variants in human primary adrenocortical tumours[J]. Clin Endocrinol, 2005, 62(5): 533-538.

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生长激素释放激素受体与肾上腺肿瘤关系的初步研究

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《华西医学》

生长激素释放激素受体与肾上腺肿瘤关系的初步研究

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