Effects of somatostatin analogs on a growth hormone-releasing hormone secreting bronchial carcinoid, in vivo and in vitro studies. 2009

M van Hoek, and L J Hofland, and Y B de Rijke, and F H van Nederveen, and R R de Krijger, and P M van Koetsveld, and S W J Lamberts, and A J van der Lely, and W W de Herder, and R A Feelders
Department of Internal Medicine-Bd289, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. m.vanhoek@erasmusmc.nl

BACKGROUND A 56-yr-old woman presented with acromegaly, a pulmonary mass, and elevated levels of GHRH, GH, and IGF-I. Histological examination revealed a bronchial carcinoid with positive staining for GHRH. Somatostatin analogs (SAs) can play an important role in the treatment of neuroendocrine tumors, dependent on the somatostatin receptor subtype (sst) expression pattern. The sst pattern in bronchial carcinoids and effects of SAs have not been extensively investigated, particularly not for the recently developed universal SA SOM230 (Pasireotide) that has high affinity for sst1, 2, 3, and 5. OBJECTIVE Our objective was to investigate the in vivo response of a GHRH-producing bronchial carcinoid to octreotide (OCT), its sst-expression profile, and in vitro responses to different SAs, including SOM230. METHODS In vivo, 50 microg OCT was administered, and plasma GH and GHRH responses were determined. In vitro, the expression of ssts was analyzed by quantitative PCR. Furthermore, the effects of SOM230 and OCT on GHRH secretion were evaluated in primary cell cultures of the carcinoid tissue. RESULTS In vivo, OCT administration fully suppressed GH and GHRH levels. In vitro, sst1 mRNA was most abundant, followed by sst2 and sst5. Both SOM230 and OCT inhibited GHRH production dose dependently (SOM230 100 nm vs. control, P = 0.01; OCT 110 nm vs. control, P = 0.05). CONCLUSIONS In this case of a GHRH-producing bronchial carcinoid, we demonstrated that SOM230 was a potent inhibitor of GHRH production in vitro and was at least equally potent compared with OCT. Therefore, SOM230 may be a potential therapeutic agent to control GHRH secretion in ectopic acromegaly.

UI MeSH Term Description Entries
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D001984 Bronchial Neoplasms Tumors or cancer of the BRONCHI. Neoplasms, Bronchial,Bronchial Neoplasm,Neoplasm, Bronchial
D002276 Carcinoid Tumor A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182) Argentaffinoma,Carcinoid,Carcinoid, Goblet Cell,Argentaffinomas,Carcinoid Tumors,Carcinoids,Carcinoids, Goblet Cell,Goblet Cell Carcinoid,Goblet Cell Carcinoids,Tumor, Carcinoid,Tumors, Carcinoid
D005260 Female Females
D006729 Hormones, Ectopic Hormones released from neoplasms or from other cells that are not the usual sources of hormones. Ectopic Hormone,Ectopic Hormones,Hormone, Ectopic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000172 Acromegaly A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80) Inappropriate Growth Hormone Secretion Syndrome (Acromegaly),Somatotropin Hypersecretion Syndrome (Acromegaly),Inappropriate GH Secretion Syndrome (Acromegaly),Hypersecretion Syndrome, Somatotropin (Acromegaly),Hypersecretion Syndromes, Somatotropin (Acromegaly),Somatotropin Hypersecretion Syndromes (Acromegaly),Syndrome, Somatotropin Hypersecretion (Acromegaly),Syndromes, Somatotropin Hypersecretion (Acromegaly)
D013004 Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal. Cyclic Somatostatin,Somatostatin-14,Somatotropin Release-Inhibiting Hormone,SRIH-14,Somatofalk,Somatostatin, Cyclic,Somatotropin Release-Inhibiting Factor,Stilamin,Somatostatin 14,Somatotropin Release Inhibiting Factor,Somatotropin Release Inhibiting Hormone
D013007 Growth Hormone-Releasing Hormone A peptide of 44 amino acids in most species that stimulates the release and synthesis of GROWTH HORMONE. GHRF (or GRF) is synthesized by neurons in the ARCUATE NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, GHRF stimulates GH release by the SOMATOTROPHS in the PITUITARY GLAND. Growth Hormone-Releasing Factor,Somatocrinin,Somatotropin-Releasing Factor 44,Somatotropin-Releasing Hormone,GHRH 1-44,GRF 1-44,Growth Hormone-Releasing Factor 44,Human Pancreatic Growth Hormone-Releasing Factor,Somatoliberin,hpGRF 44,Growth Hormone Releasing Factor,Growth Hormone Releasing Factor 44,Growth Hormone Releasing Hormone,Somatotropin Releasing Factor 44,Somatotropin Releasing Hormone
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

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