This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Ferone, D. Articles by Hofland, L. J. Search for Related Content PubMed PubMed Citation Articles by Ferone, D. Articles by Hofland, L. J.

In Vitro Characterization of Somatostatin Receptors in the Human Thymus and Effects of Somatostatin and Octreotide on Cultured Thymic Epithelial Cells

Departments of Internal Medicine III (D.F., P.M.v.H., P.M.v.K., J.Z., D.M.M., E.G.R.L.-K.), Immunology (P.M.v.H.) and Cardiothoracic Surgery (A.J.J.C.B.), Erasmus University, Rotterdam, The Netherlands; and Department of Molecular & Clinical Endocrinology and Oncology (D.F., A.C., G.L.), "Federico II" University, Naples, Italy

Address all correspondence and requests for reprints to: Leo J. Hofland, University Hospital Dijkzigt, Department of Internal Medicine III, Room Bd277, Dr Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands. E-mail: hofland{at}inw3.azr.nl

Somatostatin (SS) and its analogs exert inhibitory effects on secretive and proliferative processes of various cells via high affinity SS receptors (SS-R). SS analogs bind with different affinity to the five cloned SS-R subtypes. Octreotide, an octapeptide SS analog, binds with high affinity to the SS-R subtype 2 (sst₂). SS-R have been demonstrated in vivo and in vitro on cells from endocrine and immune systems. Among the lymphatic tissues, the thymus has been shown to contain the highest amount of SS, suggesting a local functional role of the peptide.

We investigated the SS distribution and SS-R expression pattern in the normal human thymus using autoradiography, membrane homogenate binding studies, and RT-PCR. In addition, the effect of SS and octreotide on growth of cultured thymic epithelial cells (TEC) was studied.

By autoradiography, binding of [¹²⁵I-Tyr⁰]-SS-28 and [¹²⁵I-Tyr³]-octreotide was detected in all seven thymuses studied. Specific [¹²⁵I-Tyr³]-octreotide binding was shown on membrane preparations from thymuses, while not from cultured thymocytes. RT-PCR showed the expression of sst₁, sst_2A and sst₃ messenger RNA (mRNA) in the thymic tissue, whereas sst₁ and sst_2A mRNAs were found in isolated TEC. SS mRNA was present in thymic tissue and in isolated TEC. SS and octreotide significantly inhibited ³H-thymidine incorporation in 3 of 3 and 6 of 6 TEC cultures, respectively. The percent inhibition ranged from 38.8 to 66.8% for SS and from 19.1 to 59.5% for octreotide.

In conclusion, SS mRNA and sst₁, sst_2A, and sst₃ mRNAs are expressed in the normal human thymus. Cultured TEC selectively express sst₁ and sst_2A mRNA and respond in vitro to SS and octreotide administration with an inhibition of cell proliferation. These data suggest a paracrine/autocrine role of SS and its receptors in the regulation of cell growth in thymic microenvironment.

This article has been cited by other articles:

				E. Resmini, P. Dadati, J.-L. Ravetti, G. Zona, R. Spaziante, A. Saveanu, P. Jaquet, M. D. Culler, F. Bianchi, A. Rebora, et al. Rapid Pituitary Tumor Shrinkage with Dissociation between Antiproliferative and Antisecretory Effects of a Long-Acting Octreotide in an Acromegalic Patient J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1592 - 1599. [Abstract] [Full Text] [PDF]

				D. Ferone, M. Arvigo, C. Semino, P. Jaquet, A. Saveanu, J. E. Taylor, J.-P. Moreau, M. D. Culler, M. Albertelli, F. Minuto, et al. Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1044 - E1050. [Abstract] [Full Text] [PDF]

				L. J Hofland, J. van der Hoek, R. Feelders, M. O van Aken, P. M van Koetsveld, M. Waaijers, D. Sprij-Mooij, C. Bruns, G. Weckbecker, W. W de Herder, et al. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5 Eur. J. Endocrinol., April 1, 2005; 152(4): 645 - 654. [Abstract] [Full Text] [PDF]

				R. Pivonello, D. Ferone, W. W. de Herder, R. R. de Krijger, M. Waaijers, D. M. Mooij, P. M. van Koetsveld, A. Barreca, M. L. Del Basso De Caro, G. Lombardi, et al. Dopamine Receptor Expression and Function in Human Normal Adrenal Gland and Adrenal Tumors J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4493 - 4502. [Abstract] [Full Text] [PDF]

				R. Pivonello, D. Ferone, W. W. de Herder, J. M. Kros, M. L. Del Basso De Caro, M. Arvigo, L. Annunziato, G. Lombardi, A. Colao, L. J. Hofland, et al. Dopamine Receptor Expression and Function in Corticotroph Pituitary Tumors J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2452 - 2462. [Abstract] [Full Text] [PDF]

				P. J. Loehrer Sr, W. Wang, D. H. Johnson, and D. S. Ettinger Octreotide Alone or With Prednisone in Patients With Advanced Thymoma and Thymic Carcinoma: An Eastern Cooperative Oncology Group Phase II Trial J. Clin. Oncol., January 15, 2004; 22(2): 293 - 299. [Abstract] [Full Text] [PDF]

				V. A.S.H. Dalm, L. J. Hofland, C. M. Mooy, M. A. Waaijers, P. M. van Koetsveld, A. W. Langerak, F. T.J. Staal, A.-J. van der Lely, S. W.J. Lamberts, and M. P. van Hagen Somatostatin Receptors in Malignant Lymphomas: Targets for Radiotherapy? J. Nucl. Med., January 1, 2004; 45(1): 8 - 16. [Abstract] [Full Text] [PDF]

				L. J. Hofland, S. W.J. Lamberts, P. M. van Hagen, J.-C. Reubi, J. Schaeffer, M. Waaijers, P. M. van Koetsveld, A. Srinivasan, E. P. Krenning, and W. A.P. Breeman Crucial Role for Somatostatin Receptor Subtype 2 in Determining the Uptake of [111In-DTPA-D-Phe1]Octreotide in Somatostatin Receptor-Positive Organs J. Nucl. Med., August 1, 2003; 44(8): 1315 - 1321. [Abstract] [Full Text] [PDF]

				V. A. S. H. Dalm, P. M. van Hagen, P. M. van Koetsveld, S. Achilefu, A. B. Houtsmuller, D. H. J. Pols, A.-J. van der Lely, S. W. J. Lamberts, and L. J. Hofland Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E344 - E353. [Abstract] [Full Text] [PDF]

				V. A. Dalm, P. M. van Hagen, P. M. van Koetsveld, A. W. Langerak, A.-J. van der Lely, S. W. Lamberts, and L. J. Hofland Cortistatin Rather Than Somatostatin as a Potential Endogenous Ligand for Somatostatin Receptors in the Human Immune System J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 270 - 276. [Abstract] [Full Text] [PDF]

				D. Ferone, R. Pivonello, P. M. van Hagen, V. A. S. H. Dalm, E. G. R. Lichtenauer-Kaligis, M. Waaijers, P. M. van Koetsveld, D. M. Mooy, A. Colao, F. Minuto, et al. Quantitative and functional expression of somatostatin receptor subtypes in human thymocytes Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E1056 - E1066. [Abstract] [Full Text] [PDF]

				N. J. Olsen, G. Olson, S. M. Viselli, X. Gu, and W. J. Kovacs Androgen Receptors in Thymic Epithelium Modulate Thymus Size and Thymocyte Development Endocrinology, March 1, 2001; 142(3): 1278 - 1283. [Abstract] [Full Text] [PDF]

				D. Ferone, R. Pivonello, P. M. Van Hagen, M. Waaijers, J. Zuijderwijk, A. Colao, G. Lombardi, A. J. J. C. Bogers, S. W. J. Lamberts, and L. J. Hofland Age-related decrease of somatostatin receptor number in the normal human thymus Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E791 - E798. [Abstract] [Full Text] [PDF]

				W. Savino and M. Dardenne Neuroendocrine Control of Thymus Physiology Endocr. Rev., August 1, 2000; 21(4): 412 - 443. [Abstract] [Full Text] [PDF]

				A. C. Lambooij, R. W. A. M. Kuijpers, E. G. R. van Lichtenauer–Kaligis, M. Kliffen, G. S. Baarsma, P. M. van Hagen, and C. M. Mooy Somatostatin Receptor 2A Expression in Choroidal Neovascularization Secondary to Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2329 - 2335. [Abstract] [Full Text]

				D. Ferone, M. P. van Hagen, D. J. Kwekkeboom, P. M. van Koetsveld, D. M. Mooy, E. Lichtenauer-Kaligis, A. Schönbrunn, A. Colao, S. W. J. Lamberts, and L. J. Hofland Somatostatin Receptor Subtypes in Human Thymoma and Inhibition of Cell Proliferation by Octreotide in Vitro J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1719 - 1726. [Abstract] [Full Text]