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      Differential Inhibition of Growth Hormone Secretion by Analogs Selective for Somatostatin Receptor Subtypes 2 and 5 in Human Growth-Hormone-Secreting Adenoma Cells in vitro

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          Somatostatin (SRIH), a cyclic tetradecapeptide hormone originally isolated from mammalian hypothalamus, is a potent suppressor of pituitary growth hormone (GH) secretion. SRIH acts through a family of G-protein-coupled membrane receptors containing seven transmembrane domains. Five genes encoding distinct SRIH receptor (SSTR) subtypes have so far been cloned in human and other species and termed SSTR1–5. In human somatotrophe pituitary adenomas GH secretion is controlled by both SSTR2 and SSTR5. However, in clinical practice only somatostatin analogs selective for SSTR2 (octreotide and lanreotide) are available. This may explain why clinical and in vitro responses to these analogs in acromegaly are only partial. In this study, we investigated the inhibitory effect of two new SRIH analogs with high selectivity for SSTR2 (NC-4-28B) and SSTR5 (BIM-23268) and compared it to that of native somatostatin (SRIH-14) on a large number of GH-secreting adenomas obtained by transphenoidal neurosurgery. Tissues from 16 adenomas were enzymatically dispersed and plated in 24-well dishes at 50,000 cells/well. After 3 days, groups of three wells were incubated for 4 h with medium alone, SRIH-14 or analogs NC-4-28B or BIM-23268, at the concentrations of 0.01, 0.1 and 1 µ M. Our results show that 9 out of 16 adenomas were responsive (GH suppression: 20–40% vs. control, p < 0.05) to SRIH. In this group only 4 adenomas showed similar responses to both selective analogs, with 2 nonresponders (expression of other SRIH receptor subtypes) and 2 responders (concomitant expression of SSTR2 and SSTR5) to both analogs. GH release was selectively inhibited by NC-4-28B in 3 adenomas and by BIM-23268 in the remaining 2 adenomas, suggesting predominant expression of SSTR2 and SSTR5, respectively. SRIH failed to inhibit GH release in 7 adenomas (43%). Interestingly, in that group a better inhibitory effect was obtained with BIM-23268 (5 out of 7 adenomas) than with NC-4-28B, suggesting expression of a few SSTR5 receptors only, or of both SSTR2 and SSTR5, respectively. We conclude that the availability of somatostatin analogs selective for SSTR5 will enhance the treatment potency and spectrum in acromegaly.

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          Most cited references 10

          • Record: found
          • Abstract: not found
          • Article: not found

          Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human

           A Giustina (1998)
            • Record: found
            • Abstract: not found
            • Article: not found

            Criteria for Cure of Acromegaly: A Consensus Statement 

             A Giustina (2000)
              • Record: found
              • Abstract: not found
              • Article: not found

              Molecular biology of somatostatin receptors

               T Reisine (1995)

                Author and article information

                S. Karger AG
                May 2001
                31 May 2001
                : 73
                : 5
                : 344-351
                aEndocrine Section, Department of Internal Medicine, bInstitute of Microbiology, cNeurosurgery, University of Brescia; dDivisions of Neurosurgery Hospital of Treviso; ePoliclinico Gemelli, Roma; fOspedale Maggiore, Verona, and gDivision of Endocrinology, Niguarda Hospital, Milano, Italy, and hPeptide Laboratory, Tulane University, New Orleans, La., USA
                54651 Neuroendocrinology 2001;73:344–351
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 4, Tables: 2, References: 33, Pages: 8
                Regulation of Anterior Pituitary Secretion


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