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

Dalia L. Batista, Xun Zhang, Roger Gejman, Peter J. Ansell, Yunli Zhou, Sarah A. Johnson, Brooke Swearingen, E. Tessa Hedley-Whyte, Constantine A. Stratakis and Anne Klibanski

Neuroendocrine Unit (D.L.B., X.Z., P.J.A., Y.Z., S.A.J., A.K.), Neuropathology Unit (R.G., E.T.H.-W.), and Division of Neurosurgery (B.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; and Section on Endocrinology and Genetics (D.L.B., C.A.S.), Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 02892


Address all correspondence and requests for reprints to: Anne Klibanski, M.D. Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, BUL457, Boston, Massachusetts 02114. E-mail: aklibanski@partners.org.


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.



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