This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Korbonits, M. Articles by Grossman, A. B. Search for Related Content PubMed PubMed Citation Articles by Korbonits, M. Articles by Grossman, A. B.

Expression of the Growth Hormone Secretagogue Receptor in Pituitary Adenomas and Other Neuroendocrine Tumors¹

Department of Endocrinology (M.K., R.A.J., S.J.B.A., J.M.B., P.L.M.D., J.P.M., P.J.T., S.L.C., G.M.B., A.B.G.), St. Bartholomew’s Hospital, London, United Kingdom EC1A 7BE; and Neurochirurgische Klinik der Universität Erlangen-Nürnberg (J.H., R.F.), 91054 Erlangen, Germany

Address all correspondence and requests for reprints to: Prof. A. B. Grossman, Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, United Kingdom EC1A 7BE. E-mail: a.b.grossman{at}mds.qmw.ac.uk

Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide mimetics) stimulate GH release, activate the hypothalamo-pituitary-adrenal axis, and release PRL in vivo. Patients with acromegaly show an exuberant GH response to GHSs, whereas patients with pituitary-dependent ACTH-secreting tumors show an exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3 insulinomas, and a nonsecreting thymic carcinoid as well as in 7 normal pituitary glands. Certain pituitary tumors were also studied by in vitro cell culture with measurement of secreted GH, ACTH, PRL, FSH, LH, -subunit, and TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R expression.

All the somatotroph adenomas (n = 8) showed a 2–10 times higher expression of the GHS-R gene compared to normal pituitaries. Higher than normal expression was shown in 5 of 18 tumors from patients with ACTH-secreting pituitary adenomas and in 1 of 3 ectopic ACTH-secreting carcinoid tumors. Two of the pituitary ACTH-secreting adenoma samples showed completely absent expression of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and 3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors showed a very low level of expression. One of 4 prolactinoma samples showed a high level of expression, 1 showed expression similar to that of normal pituitary, and 2 samples showed a very low level of expression. Nonfunctioning pituitary adenoma samples showed either absent or very low level expression of the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of normal pituitary tissue, whereas 3 insulinomas showed low level expression of the GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable expression.

In summary, although GHS-R messenger RNA is abundant in human somatotroph adenomas, it is also present in other pituitary adenomas, particularly ACTH-secreting tumors. These findings may explain the in vivo responses to GHSs in patients harboring such tumors. It also appears from our study that GHS-R may be expressed in other neuroendocrine tumors.

This article has been cited by other articles:

				M. C. Machado, S. Valeria de Sa, M. L. Correa-Giannella, R. R. Giorgi, M. A. A. Pereira, V. A. S Cescato, D. Giannella-Neto, and L. R. Salgado Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing's syndrome patients Eur. J. Endocrinol., May 1, 2008; 158(5): 605 - 613. [Abstract] [Full Text] [PDF]

				M. Kidd, B. Nadler, S. Mane, G. Eick, M. Malfertheiner, M. Champaneria, R. Pfragner, and I. Modlin GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR Physiol Genomics, August 20, 2007; 30(3): 363 - 370. [Abstract] [Full Text] [PDF]

				H D. Falls, B. D Dayton, D. G Fry, C. A Ogiela, V. G Schaefer, S. Brodjian, R. M Reilly, C. A Collins, and W. Kaszubska Characterization of ghrelin receptor activity in a rat pituitary cell line RC-4B/C. J. Mol. Endocrinol., August 1, 2006; 37(1): 51 - 62. [Abstract] [Full Text] [PDF]

				S Pekic, M Doknic, D Miljic, M Joksimovic, J Glodic, M Djurovic, C Dieguez, F Casanueva, and V Popovic Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly. Eur. J. Endocrinol., May 1, 2006; 154(5): 659 - 666. [Abstract] [Full Text] [PDF]

				A. H. Yeh, P. L. Jeffery, R. P. Duncan, A. C. Herington, and L. K. Chopin Ghrelin and a Novel Preproghrelin Isoform Are Highly Expressed in Prostate Cancer and Ghrelin Activates Mitogen-Activated Protein Kinase in Prostate Cancer Clin. Cancer Res., December 1, 2005; 11(23): 8295 - 8303. [Abstract] [Full Text] [PDF]

				A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin Endocr. Rev., June 1, 2004; 25(3): 426 - 457. [Abstract] [Full Text] [PDF]

				F. Gaytan, M. L. Barreiro, J. E. Caminos, L. K. Chopin, A. C. Herington, C. Morales, L. Pinilla, R. Paniagua, M. Nistal, F. F. Casanueva, et al. Expression of Ghrelin and Its Functional Receptor, the Type 1a Growth Hormone Secretagogue Receptor, in Normal Human Testis and Testicular Tumors J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 400 - 409. [Abstract] [Full Text] [PDF]

				P. U. Freda, C. M. Reyes, I. M. Conwell, R. E. Sundeen, and S. L. Wardlaw Serum Ghrelin Levels in Acromegaly: Effects of Surgical and Long-Acting Octreotide Therapy J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2037 - 2044. [Abstract] [Full Text] [PDF]

				M. Korbonits, H. S. Chahal, G. Kaltsas, S. Jordan, Y. Urmanova, Z. Khalimova, P. E. Harris, W. E. Farrell, F.-X. Claret, and A. B. Grossman Expression of Phosphorylated p27Kip1 Protein and Jun Activation Domain-Binding Protein 1 in Human Pituitary Tumors J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2635 - 2643. [Abstract] [Full Text] [PDF]

				M. Volante, E. AllIa, P. Gugliotta, A. Funaro, F. Broglio, R. Deghenghi, G. Muccioli, E. Ghigo, and M. Papotti Expression of Ghrelin and of the GH Secretagogue Receptor by Pancreatic Islet Cells and Related Endocrine Tumors J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1300 - 1308. [Abstract] [Full Text] [PDF]

				M. Papotti, P. Cassoni, M. Volante, R. Deghenghi, G. Muccioli, and E. Ghigo Ghrelin-Producing Endocrine Tumors of the Stomach and Intestine J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 5052 - 5059. [Abstract] [Full Text] [PDF]

				S. Petersenn, A. C. Rasch, M. Penshorn, F. U. Beil, and H. M. Schulte Genomic Structure and Transcriptional Regulation of the Human Growth Hormone Secretagogue Receptor Endocrinology, June 1, 2001; 142(6): 2649 - 2659. [Abstract] [Full Text] [PDF]

				P. Cassoni, M. Papotti, C. Ghè, F. Catapano, A. Sapino, A. Graziani, R. Deghenghi, T. Reissmann, E. Ghigo, and G. Muccioli Identification, Characterization, and Biological Activity of Specific Receptors for Natural (Ghrelin) and Synthetic Growth Hormone Secretagogues and Analogs in Human Breast Carcinomas and Cell Lines J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1738 - 1745. [Abstract] [Full Text]

				X.-d. Peng, S. Park, M. R. Gadelha, K. T. Coschigano, J. J. Kopchick, L. A. Frohman, and R. D. Kineman The Growth Hormone (GH)-Axis of GH Receptor/Binding Protein Gene-Disrupted and Metallothionein-Human GH-Releasing Hormone Transgenic Mice: Hypothalamic Neuropeptide and Pituitary Receptor Expression in the Absence and Presence of GH Feedback Endocrinology, March 1, 2001; 142(3): 1117 - 1123. [Abstract] [Full Text] [PDF]

				M. Korbonits, S. A. Bustin, M. Kojima, S. Jordan, E. F. Adams, D. G. Lowe, K. Kangawa, and A. B. Grossman The Expression of the Growth Hormone Secretagogue Receptor Ligand Ghrelin in Normal and Abnormal Human Pituitary and Other Neuroendocrine Tumors J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 881 - 887. [Abstract] [Full Text]

				M. Papotti, C. Ghè, P. Cassoni, F. Catapano, R. Deghenghi, E. Ghigo, and G. Muccioli Growth Hormone Secretagogue Binding Sites in Peripheral Human Tissues J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3803 - 3807. [Abstract] [Full Text]

				K. Lidhar, M. Korbonits, S. Jordan, Z. Khalimova, G. Kaltsas, X. Lu, R. N. Clayton, P. J. Jenkins, J. P. Monson, G. M. Besser, et al. Low Expression of the Cell Cycle Inhibitor p27Kip1 in Normal Corticotroph Cells, Corticotroph Tumors, and Malignant Pituitary Tumors J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3823 - 3830. [Abstract] [Full Text] [PDF]

				P. L. M. Dahia and A. B. Grossman The Molecular Pathogenesis of Corticotroph Tumors Endocr. Rev., April 1, 1999; 20(2): 136 - 155. [Abstract] [Full Text]