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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Jun;150(6):1885–1891.

Growth hormone-releasing hormone receptor mRNA in acromegalic pituitary tumors.

M B Lopes 1, B D Gaylinn 1, M O Thorner 1, M H Stoler 1
PMCID: PMC1858316  PMID: 9176381

Abstract

The growth hormone (GH)-releasing hormone receptor (GHRH-R) has been recently cloned and found to be a member of a new family of seven transmembrane receptors that includes secretin, vasoactive intestinal peptide, calcitonin, and corticotropin-releasing factor. GHRH-R mRNA has been demonstrated by Northern blot analyses to be present specifically in the anterior pituitary gland. To determine the precise cellular localization of this receptor in normal anterior pituitary and pituitary adenomas, GHRH-R mRNA was analyzed in 2 normal human pituitary glands and 16 human pituitary adenomas using in situ hybridization. GHRH-R was specifically localized in somatotroph cells in the normal pituitary. In the adenomas, all GH-producing adenomas originating from acromegalic patients demonstrated up-regulation of GHRH-R mRNA when compared with levels in the normal pituitary. Only one of five clinically nonfunctioning adenomas, a gonadotroph luteinizing hormone/follicle-stimulating hormone-positive adenoma, exhibited up-regulation of this receptor message. Adrenocorticotrophic hormone-secreting and prolactin-secreting adenomas did not express GHRH-R message. In summary, GHRH-R is specifically expressed in somatotrophs and GH-producing adenomas, suggesting that GHRH-R may influence GH release in adenomas similar to this receptor's actions in the normal somatotrophs and may be involved in the growth of GH-secreting adenomas.

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Selected References

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  1. Alexander J. M., Biller B. M., Bikkal H., Zervas N. T., Arnold A., Klibanski A. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest. 1990 Jul;86(1):336–340. doi: 10.1172/JCI114705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asa S. L., Kovacs K., Thorner M. O., Leong D. A., Rivier J., Vale W. Immunohistological localization of growth hormone-releasing hormone in human tumors. J Clin Endocrinol Metab. 1985 Mar;60(3):423–427. doi: 10.1210/jcem-60-3-423. [DOI] [PubMed] [Google Scholar]
  3. Asa S. L., Scheithauer B. W., Bilbao J. M., Horvath E., Ryan N., Kovacs K., Randall R. V., Laws E. R., Jr, Singer W., Linfoot J. A. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab. 1984 May;58(5):796–803. doi: 10.1210/jcem-58-5-796. [DOI] [PubMed] [Google Scholar]
  4. Billestrup N., Swanson L. W., Vale W. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6854–6857. doi: 10.1073/pnas.83.18.6854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooper J. A. Oncogenes and anti-oncogenes. Curr Opin Cell Biol. 1990 Apr;2(2):285–295. doi: 10.1016/0955-0674(90)90021-6. [DOI] [PubMed] [Google Scholar]
  6. Cronin M. J., Rogol A. D., Dabney L. G., Thorner M. O. Selective growth hormone and cyclic AMP stimulating activity is present in human pancreatic islet cell tumor. J Clin Endocrinol Metab. 1982 Aug;55(2):381–383. doi: 10.1210/jcem-55-2-381. [DOI] [PubMed] [Google Scholar]
  7. Cronin M. J., Rogol A. D., MacLeod R. M., Keefer D. A., Login I. S., Borges J. L., Thorner M. O. Biological activity of a growth hormone-releasing factor secreted by a human tumor. Am J Physiol. 1983 Apr;244(4):E346–E353. doi: 10.1152/ajpendo.1983.244.4.E346. [DOI] [PubMed] [Google Scholar]
  8. Gaylinn B. D., Harrison J. K., Zysk J. R., Lyons C. E., Lynch K. R., Thorner M. O. Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Mol Endocrinol. 1993 Jan;7(1):77–84. doi: 10.1210/mend.7.1.7680413. [DOI] [PubMed] [Google Scholar]
  9. Godfrey P., Rahal J. O., Beamer W. G., Copeland N. G., Jenkins N. A., Mayo K. E. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet. 1993 Jul;4(3):227–232. doi: 10.1038/ng0793-227. [DOI] [PubMed] [Google Scholar]
  10. Guillemin R., Brazeau P., Böhlen P., Esch F., Ling N., Wehrenberg W. B. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982 Nov 5;218(4572):585–587. doi: 10.1126/science.6812220. [DOI] [PubMed] [Google Scholar]
  11. Herman V., Fagin J., Gonsky R., Kovacs K., Melmed S. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab. 1990 Dec;71(6):1427–1433. doi: 10.1210/jcem-71-6-1427. [DOI] [PubMed] [Google Scholar]
  12. Landis C. A., Masters S. B., Spada A., Pace A. M., Bourne H. R., Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989 Aug 31;340(6236):692–696. doi: 10.1038/340692a0. [DOI] [PubMed] [Google Scholar]
  13. Leveston S. A., McKeel D. W., Jr, Buckley P. J., Deschryver K., Greider M. H., Jaffe B. M., Daughaday W. H. Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor. J Clin Endocrinol Metab. 1981 Oct;53(4):682–689. doi: 10.1210/jcem-53-4-682. [DOI] [PubMed] [Google Scholar]
  14. Lin C., Lin S. C., Chang C. P., Rosenfeld M. G. Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth. Nature. 1992 Dec 24;360(6406):765–768. doi: 10.1038/360765a0. [DOI] [PubMed] [Google Scholar]
  15. Lin S. C., Lin C. R., Gukovsky I., Lusis A. J., Sawchenko P. E., Rosenfeld M. G. Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature. 1993 Jul 15;364(6434):208–213. doi: 10.1038/364208a0. [DOI] [PubMed] [Google Scholar]
  16. Lloyd R. V., Jin L., Chang A., Kulig E., Camper S. A., Ross B. D., Downs T. R., Frohman L. A. Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis. Am J Pathol. 1992 Oct;141(4):895–906. [PMC free article] [PubMed] [Google Scholar]
  17. Mayo K. E., Hammer R. E., Swanson L. W., Brinster R. L., Rosenfeld M. G., Evans R. M. Dramatic pituitary hyperplasia in transgenic mice expressing a human growth hormone-releasing factor gene. Mol Endocrinol. 1988 Jul;2(7):606–612. doi: 10.1210/mend-2-7-606. [DOI] [PubMed] [Google Scholar]
  18. Mayo K. E. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992 Oct;6(10):1734–1744. doi: 10.1210/mend.6.10.1333056. [DOI] [PubMed] [Google Scholar]
  19. Rivier J., Spiess J., Thorner M., Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982 Nov 18;300(5889):276–278. doi: 10.1038/300276a0. [DOI] [PubMed] [Google Scholar]
  20. Saeed uz Zafar M., Mellinger R. C., Fine G., Szabo M., Frohman L. A. Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity. J Clin Endocrinol Metab. 1979 Jan;48(1):66–71. doi: 10.1210/jcem-48-1-66. [DOI] [PubMed] [Google Scholar]
  21. Seifert H., Perrin M., Rivier J., Vale W. Binding sites for growth hormone releasing factor on rat anterior pituitary cells. Nature. 1985 Feb 7;313(6002):487–489. doi: 10.1038/313487a0. [DOI] [PubMed] [Google Scholar]
  22. Seifert H., Perrin M., Rivier J., Vale W. Growth hormone-releasing factor binding sites in rat anterior pituitary membrane homogenates: modulation by glucocorticoids. Endocrinology. 1985 Jul;117(1):424–426. doi: 10.1210/endo-117-1-424. [DOI] [PubMed] [Google Scholar]
  23. Thorner M. O., Perryman R. L., Cronin M. J., Rogol A. D., Draznin M., Johanson A., Vale W., Horvath E., Kovacs K. Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. J Clin Invest. 1982 Nov;70(5):965–977. doi: 10.1172/JCI110708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vallar L., Spada A., Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature. 1987 Dec 10;330(6148):566–568. doi: 10.1038/330566a0. [DOI] [PubMed] [Google Scholar]
  25. Wajnrajch M. P., Gertner J. M., Harbison M. D., Chua S. C., Jr, Leibel R. L. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet. 1996 Jan;12(1):88–90. doi: 10.1038/ng0196-88. [DOI] [PubMed] [Google Scholar]
  26. Zysk J. R., Gaylinn B. D., Lyons C. E., Johnson B., Eppler C. M., Baumbach W. R., Thorner M. O. Purification of the growth hormone releasing hormone receptor with a C-terminal, biotinylated affinity ligand. Biochem Biophys Res Commun. 1996 Apr 5;221(1):133–139. doi: 10.1006/bbrc.1996.0540. [DOI] [PubMed] [Google Scholar]

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