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Original Studies |
Department of Endocrinology (M.K., A.B.G.), Academic Department of Surgery (S.A.B.), and Department of Histopathology (S.J., D.G.L.), St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, United Kingdom EC1A 7BE; Department of Biochemistry, National Cardiovascular Center Institute (M.K., K.K.), Suita, Osaka 565-8565, Japan; and Pharmaceutical Sciences Institute (E.F.A.), Aston University, Birmingham B4 7ET, United Kingdom
Address all correspondence and requests for reprints to: Ashley Grossman, M.D., Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, United Kingdom EC1A 7BE. E-mail: a.b.grossmann{at}mds.qmw.ac.uk
Ghrelin is a recently identified endogenous ligand of the GH secretagogue (GHS) receptor. It was originally isolated from the stomach, but has also been shown to be present in the rat hypothalamus. It is a 28-amino acid peptide with an unusual octanoylated serine 3 at the N-terminal end of the molecule, which is crucial for its biological activity. Synthetic GHSs stimulate GH release via both the hypothalamus and the pituitary, and the GHS receptor (GHS-R) has been shown by us and others to be present in the pituitary. We investigated whether ghrelin messenger ribonucleic acid (mRNA) and peptide are present in the normal human hypothalamus and in normal and adenomatous human pituitary.
RNA was extracted from pituitary tissue removed at autopsy and transsphenoidal surgery (n = 62), and ghrelin and GHS-R type 1a and 1b mRNA levels were investigated using real-time RT-PCR. Both ghrelin and GHS-R mRNA were detected in all samples. Corticotroph tumors showed significantly less expression of ghrelin mRNA, whereas GHS-R mRNA levels were similar to those in normal pituitary tissue. Gonadotroph tumors showed a particularly low level of expression of GHS-R mRNA. Immunohistochemistry, using a polyclonal antibody against the C-terminal end of the ghrelin molecule, revealed positive staining in the homolog of the arcuate nucleus in the human hypothalamus and in both normal and abnormal human pituitary. Pituitary tumor ghrelin peptide content was demonstrated using two separate RIA reactions for the N-terminal and C-terminal ends of the molecule. Both forms were present in normal and abnormal pituitaries, with 5 ± 2.5% octanoylated (active) ghrelin (mean ± SD) present as a percentage of the total. We suggest that the presence of ghrelin mRNA and peptide in the pituitary implies that the locally synthesized hormone may have an autocrine/paracrine modulatory effect on pituitary hormone release.
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A. P. Goldstone, E. L. Thomas, A. E. Brynes, G. Castroman, R. Edwards, M. A. Ghatei, G. Frost, A. J. Holland, A. B. Grossman, M. Korbonits, et al. Elevated Fasting Plasma Ghrelin in Prader-Willi Syndrome Adults Is Not Solely Explained by Their Reduced Visceral Adiposity and Insulin Resistance J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1718 - 1726. [Abstract] [Full Text] [PDF]
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J. P. Camina, M. C. Carreira, S. El Messari, C. Llorens-Cortes, R. G. Smith, and F. F. Casanueva Desensitization and Endocytosis Mechanisms of Ghrelin-Activated Growth Hormone Secretagogue Receptor 1a Endocrinology, February 1, 2004; 145(2): 930 - 940. [Abstract] [Full Text] [PDF]
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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]
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 K. L.J. Ellacott and R. D. Cone The Central Melanocortin System and the Integration of Short- and Long-term Regulators of Energy Homeostasis Recent Prog. Horm. Res., January 1, 2004; 59(1): 395 - 408. [Abstract] [Full Text]
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G. Arnaldi, T. Mancini, B. Kola, G. Appolloni, S. Freddi, C. Concettoni, I. Bearzi, A. Masini, M. Boscaro, and F. Mantero Cyclical Cushing's Syndrome in a Patient with a Bronchial Neuroendocrine Tumor (Typical Carcinoid) Expressing Ghrelin and Growth Hormone Secretagogue Receptors J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5834 - 5840. [Abstract] [Full Text] [PDF]
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J. E. Caminos, R. Nogueiras, M. Blanco, L. M. Seoane, S. Bravo, C. V. Alvarez, T. Garcia-Caballero, F. F. Casanueva, and C. Dieguez Cellular Distribution and Regulation of Ghrelin Messenger Ribonucleic Acid in the Rat Pituitary Gland Endocrinology, November 1, 2003; 144(11): 5089 - 5097. [Abstract] [Full Text] [PDF]
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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]
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G. S. Tannenbaum, J. Epelbaum, and C. Y. Bowers Interrelationship between the Novel Peptide Ghrelin and Somatostatin/Growth Hormone-Releasing Hormone in Regulation of Pulsatile Growth Hormone Secretion Endocrinology, March 1, 2003; 144(3): 967 - 974. [Abstract] [Full Text] [PDF]
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N. Moller, J. Nygren, T. K. Hansen, H. Orskov, J. Frystyk, and K. S. Nair Splanchnic Release of Ghrelin in Humans J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 850 - 852. [Abstract] [Full Text] [PDF]
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 M. Volante, E. Allia, E. Fulcheri, P. Cassoni, E. Ghigo, G. Muccioli, and M. Papotti Ghrelin in Fetal Thyroid and Follicular Tumors and Cell Lines: Expression and Effects on Tumor Growth Am. J. Pathol., February 1, 2003; 162(2): 645 - 654. [Abstract] [Full Text] [PDF]
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 H. Hosoda, M. Kojima, and K. Kangawa Ghrelin and the Regulation of Food Intake and Energy Balance Mol. Interv., December 1, 2002; 2(8): 494 - 503. [Abstract] [Full Text]
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H. Iwakura, K. Hosoda, R. Doi, I. Komoto, H. Nishimura, C. Son, J. Fujikura, T. Tomita, K. Takaya, Y. Ogawa, et al. Ghrelin Expression in Islet Cell Tumors: Augmented Expression of Ghrelin in a Case of Glucagonoma with Multiple Endocrine Neoplasm Type I J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4885 - 4888. [Abstract] [Full Text] [PDF]
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H. Tamura, J. Kamegai, T. Shimizu, S. Ishii, H. Sugihara, and S. Oikawa Ghrelin Stimulates GH But Not Food Intake in Arcuate Nucleus Ablated Rats Endocrinology, September 1, 2002; 143(9): 3268 - 3275. [Abstract] [Full Text] [PDF]
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M. Volante, E. Fulcheri, E. Allia, M. Cerrato, A. Pucci, and M. Papotti Ghrelin Expression in Fetal, Infant, and Adult Human Lung J. Histochem. Cytochem., August 1, 2002; 50(8): 1013 - 1021. [Abstract] [Full Text] [PDF]
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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]
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C. Ghe, P. Cassoni, F. Catapano, T. Marrocco, R. Deghenghi, E. Ghigo, G. Muccioli, and M. Papotti The Antiproliferative Effect of Synthetic Peptidyl GH Secretagogues in Human CALU-1 Lung Carcinoma Cells Endocrinology, February 1, 2002; 143(2): 484 - 491. [Abstract] [Full Text] [PDF]
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N. Kanamoto, T. Akamizu, H. Hosoda, Y. Hataya, H. Ariyasu, K. Takaya, K. Hosoda, M. Saijo, K. Moriyama, A. Shimatsu, et al. Substantial Production of Ghrelin by a Human Medullary Thyroid Carcinoma Cell Line J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4984 - 4990. [Abstract] [Full Text] [PDF]
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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]
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