The Effects of SOM230 on Cell Proliferation and Adrenocorticotropin Secretion in Human Corticotroph Pituitary Adenomas

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 11; pp. 4482 - 4488
• Main Authors: Batista, Dalia L., Zhang, Xun, Gejman, Roger, Ansell, Peter J., Zhou, Yunli, Johnson, Sarah A., Swearingen, Brooke, Hedley-Whyte, E. Tessa, Stratakis, Constantine A., Klibanski, Anne
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2006; Copyright by The Endocrine Society
• Subjects: ACTH-Secreting Pituitary Adenoma - drug therapy; Adenoma - drug therapy; Adolescent; Adrenocorticotropic Hormone - secretion; Adult; Biological and medical sciences; Cell Proliferation - drug effects; Child; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Immunohistochemistry; In Vitro Techniques; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary ACTH Hypersecretion - drug therapy; Receptors, Somatostatin - metabolism; RNA, Messenger - metabolism; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Somatostatin - therapeutic use; Tumor Cells, Cultured; Vertebrates: endocrinology; Endocrinopathy; Human; Cell proliferation; Adrenocorticotropic hormone; Adenohypophyseal hormone; Secretion; Adrenal hormone; Pituitary diseases; Pituitary Adenoma; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-1245

Context: There is no tumor-directed medical therapy available for Cushing’s disease. Objective: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. Design/Methods: Expression of somatostatin receptors (SSTR 1–5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. Results: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10–70%; P = 0.045–0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23–56%; P = 0.042–0.001). Conclusion: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.