Journal of Clinical Endocrinology & Metabolism, Vol 79, 1457-1464, Copyright © 1994 by Endocrine Society

ARTICLES

Presence of somatostatin receptors negatively coupled to adenylate cyclase in ectopic growth hormone-releasing hormone- and alpha-subunit- secreting tumors from acromegalic patients responsive to octreotide

J Bertherat, G Turpin, C Rauch, JY Li, J Epelbaum, G Sassolas and G Schaison
Peptide Biology Laboratory, Salk Institute, La Jolla, California 92186- 5800.

The functional study of SRIH receptors was performed in ectopic GHRH- secreting tumors from two patients with acromegaly; patient 1 presented with multiple endocrine neoplasia type 1 with GHRH- and insulin- secreting pancreatic tumors, and patient 2 presented with a multihormone-secreting carcinoid tumor (including GHRH and alpha- subunit secretion, as demonstrated by clinical and immunohistochemical studies). In both cases, plasma GH levels were responsive to octreotide. In patient 2, plasma GHRH and alpha-subunit levels were responsive to octreotide. In vitro perifusion studies of a tumor fragment from patient 1 also showed inhibition of GHRH secretion by SRIH. A high density of specific SRIH-binding sites was visualized by autoradiography in GHRH tumors from both patients. SRIH specific binding was much higher in the GHRH tumors (6.6-8.4 fmol/surface unit) than in the insulinoma (1.9 fmol/surface unit). The binding inhibition constant (IC50) was in the nanomolar range (0.9-3 nmol/L) in the GHRH tumors. SRIH-14 inhibited forskolin-stimulated adenylate cyclase in the GHRH tumors from both patients, but not in the insulinoma. The functional SRIH receptors negatively coupled to adenylate cyclase present in ectopic GHRH-secreting tumors mediate the inhibitory effect of octreotide on GHRH secretion and on previously underrecognized ectopic alpha-subunit secretion from carcinoid tumors.

This article has been cited by other articles:

				K. M A Dreijerink, A. P van Beek, E. G W M Lentjes, J. G Post, R. B van der Luijt, M. R C.-v. Dijk, and C. J M Lips Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease Eur. J. Endocrinol., December 1, 2005; 153(6): 741 - 746. [Abstract] [Full Text] [PDF]

				M. C. Zatelli, P. Maffei, D. Piccin, C. Martini, F. Rea, D. Rubello, A. Margutti, M. D. Culler, N. Sicolo, and E. C. d. Uberti Somatostatin Analogs in Vitro Effects in a Growth Hormone-Releasing Hormone-Secreting Bronchial Carcinoid J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2104 - 2109. [Abstract] [Full Text] [PDF]

				J. Bertherat, F. Tenenbaum, K. Perlemoine, C. Videau, J. L. Alberini, B. Richard, B. Dousset, X. Bertagna, and J. Epelbaum Somatostatin Receptors 2 and 5 Are the Major Somatostatin Receptors in Insulinomas: An in Vivo and in Vitro Study J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5353 - 5360. [Abstract] [Full Text] [PDF]

				A. Van den Bruel, J. Fevery, J. Van Dorpe, L. Hofland, and R. Bouillon Hormonal and Volumetric Long Term Control of a Growth Hormone-Releasing Hormone-Producing Carcinoid Tumor J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3162 - 3169. [Full Text]

				P. Chanson, J. Pantel, J. Young, B. Couzinet, J.-M. Bidart, and G. Schaison Free Luteinizing-Hormone Beta-Subunit in Normal Subjects and Patients with Pituitary Adenomas J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1397 - 1402. [Abstract] [Full Text] [PDF]