Journal of Clinical Endocrinology & Metabolism, Vol 71, 1421-1426, Copyright © 1990 by Endocrine Society

ARTICLES

Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase

A Spada, M Arosio, D Bochicchio, N Bazzoni, L Vallar, M Bassetti and G Faglia
Institute of Endocrine Sciences, University of Milan, Italy.

Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH- secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine- induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.

This article has been cited by other articles:

				T. Miyoshi, F. Otsuka, H. Otani, K. Inagaki, J. Goto, M. Yamashita, T. Ogura, Y. Iwasaki, and H. Makino Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells J. Endocrinol., April 1, 2008; 197(1): 159 - 169. [Abstract] [Full Text] [PDF]

				S. L. Asa, R. DiGiovanni, J. Jiang, M. L. Ward, K. Loesch, S. Yamada, T. Sano, K. Yoshimoto, S. J. Frank, and S. Ezzat A Growth Hormone Receptor Mutation Impairs Growth Hormone Autofeedback Signaling in Pituitary Tumors Cancer Res., August 1, 2007; 67(15): 7505 - 7511. [Abstract] [Full Text] [PDF]

				I. Donangelo, S. Gutman, E. Horvath, K. Kovacs, K. Wawrowsky, M. Mount, and S. Melmed Pituitary Tumor Transforming Gene Overexpression Facilitates Pituitary Tumor Development Endocrinology, October 1, 2006; 147(10): 4781 - 4791. [Abstract] [Full Text] [PDF]

				S. Bhayana, G. L. Booth, S. L. Asa, K. Kovacs, and S. Ezzat The Implication of Somatotroph Adenoma Phenotype to Somatostatin Analog Responsiveness in Acromegaly J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6290 - 6295. [Abstract] [Full Text] [PDF]

				R Chetty and S L Asa Pancreatic endocrine tumour with cytoplasmic keratin whorls. Is the term "rhabdoid" appropriate? J. Clin. Pathol., October 1, 2004; 57(10): 1106 - 1110. [Abstract] [Full Text] [PDF]

				A. Lania, G. Mantovani, and A. Spada Genetics of Pituitary Tumors: Focus on G-Protein Mutations Experimental Biology and Medicine, October 1, 2003; 228(9): 1004 - 1017. [Abstract] [Full Text] [PDF]

				A. Lania, M. Filopanti, S. Corbetta, M. Losa, E. Ballare, P. Beck-Peccoz, and A. Spada Effects of Hypothalamic Neuropeptides on Extracellular Signal-Regulated Kinase (ERK1 and ERK2) Cascade in Human Tumoral Pituitary Cells J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1692 - 1696. [Abstract] [Full Text] [PDF]

				Ph. Caron, A. Beckers, D. R. Cullen, M. I. Goth, B. Gutt, P. Laurberg, A. M. Pico, M. Valimaki, and W. Zgliczynski Efficacy of the New Long-Acting Formulation of Lanreotide (Lanreotide Autogel) in the Management of Acromegaly J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 99 - 104. [Abstract] [Full Text] [PDF]

				L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting Endocr. Rev., October 1, 2001; 22(5): 675 - 705. [Abstract] [Full Text] [PDF]

				R. D. Kineman, L. T. Teixeira, G. V. Amargo, K. T. Coschigano, J. J. Kopchick, and L. A. Frohman The Effect of GHRH on Somatotrope Hyperplasia and Tumor Formation in the Presence and Absence of GH Signaling Endocrinology, September 1, 2001; 142(9): 3764 - 3773. [Abstract] [Full Text] [PDF]

				E. Ballare, L. Persani, A. G. Lania, M. Filopanti, E. Giammona, S. Corbetta, S. Mantovani, M. Arosio, P. Beck-Peccoz, G. Faglia, et al. Mutation of Somatostatin Receptor Type 5 in an Acromegalic Patient Resistant to Somatostatin Analog Treatment J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3809 - 3814. [Abstract] [Full Text] [PDF]

				A. Peri, B. Conforti, S. Baglioni-Peri, P. Luciani, F. Cioppi, L. Buci, S. Corbetta, E. Ballaré, M. Serio, and A. Spada Expression of Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Responsive Element Binding Protein and Inducible-cAMP Early Repressor Genes in Growth Hormone-Secreting Pituitary Adenomas with or without Mutations of the Gs{{alpha}} Gene J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2111 - 2117. [Abstract] [Full Text]

				A. Barlier, I. Pellegrini-Bouiller, G. Gunz, A. J. Zamora, P. Jaquet, and A. Enjalbert Impact of gsp Oncogene on the Expression of Genes Coding for Gs{alpha}, Pit-1, Gi2{alpha}, and Somatostatin Receptor 2 in Human Somatotroph Adenomas: Involvement in Octreotide Sensitivity J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2759 - 2765. [Abstract] [Full Text]

				C. J. McCabe, N. J. Gittoes, M. C. Sheppard, and J. A. Franklyn Thyroid Receptor {alpha}1 and {alpha}2 Mutations in Nonfunctioning Pituitary Tumors J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 649 - 653. [Abstract] [Full Text]

				S. L. Asa and S. Ezzat The Cytogenesis and Pathogenesis of Pituitary Adenomas Endocr. Rev., December 1, 1998; 19(6): 798 - 827. [Abstract] [Full Text]

				A. Barlier, G. Gunz, A. J. Zamora, I. Morange-Ramos, D. Figarella-Branger, H. Dufour, A. Enjalbert, and P. Jaquet Pronostic and Therapeutic Consequences of Gs{alpha} Mutations in Somatotroph Adenomas J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1604 - 1610. [Abstract] [Full Text]

				A. Lania, L. Persani, E. Ballaré, S. Mantovani, M. Losa, and A. Spada Constitutively Active Gs{alpha} Is Associated with an Increased Phosphodiesterase Activity in Human Growth Hormone-Secreting Adenomas J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1624 - 1628. [Abstract] [Full Text]

				I. Yang, S. Park, J. Woo, S. Kim, J. Kim, Y. Kim, and Y. Choi Growth Hormone Response to the Hypothalamic Somatostatinergic Activity in Acromegalic Patients J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2492 - 2496. [Abstract] [Full Text] [PDF]

				I. Shimon and S. Melmed Pituitary Tumor Pathogenesis J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1675 - 1681. [Full Text] [PDF]

				N. J. L. Gittoes, C. J. McCabe, J. Verhaeg, M. C. Sheppard, and J. A. Franklyn Thyroid Hormone and Estrogen Receptor Expression in Normal Pituitary and Nonfunctioning Tumors of the Anterior Pituitary J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1960 - 1967. [Abstract] [Full Text] [PDF]

				C. L. Boguszewski, G. Johannsson, B.-A. Bengtsson, A. Johansson, B. Carlsson, and L. M. S. Carlsson Circulating Non-22-Kilodalton Growth Hormone Isoforms in Acromegalic Men before and after Transsphenoidal Surgery J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1516 - 1521. [Abstract] [Full Text] [PDF]