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Cedars Sinai Research Institute (R.D.M., K.K., S.-G.R., S.M.), University of California Los Angeles School of Medicine, Los Angeles, California 90048; and Novartis Pharma AG (I.L., G.W., C.B.), CH-4002 Basel, Switzerland
Address all correspondence and requests for reprints to: Shlomo Melmed, M.D., Room 2015, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu.
Currently available somatostatin analogs predominantly bind to the somatostatin receptor subtype (SSTR)2 subtype, and control GH and IGF-I secretion in approximately 65% of patients with acromegaly, their efficacy relating to receptor density and subtype expression. SOM230 is a somatostatin ligand with high affinity to four SSTR subtypes. In primary cultures of rat pituicytes, SOM230 dose-dependently inhibited GH release (P = 0.002) with an IC50 of 1.2 nM. Ten nanomoles SOM230 inhibited GH and TSH release by 40 ± 7% (P < 0.001) and 47 ± 21% (P = 0.09), respectively. No effect of SOM230 was observed on prolactin (PRL) or LH release. In cultures of human fetal pituitary cells, SOM230 inhibited GH secretion by 42 ± 9% (P = 0.002) but had no effect on TSH release. SOM230 inhibited GH release from GH-secreting adenoma cultures by 34 ± 8% (P = 0.002), PRL by 35 ± 4% from PRL-secreting adenomas (P = 0.01), and 
-subunit secretion from nonfunctioning pituitary adenomas by 46 ± 18% (P = 0.34). In contrast, octreotide inhibited GH, PRL, and -subunit from the respective adenoma by 18 ± 12 (P = 0.39), 22 ± 4 (P = 0.04), and 20 ± 10% (P = 0.34). In all culture systems, no significant difference in the inhibitory action of SOM230, octreotide, and somatostatin 14 on hormone release was observed. SOM230, similar to somatostatin, has high-affinity binding to SSTR1, 2, 3, and 5 and, in keeping with this, has an equivalent inhibitory effect on pituitary hormone secretion. As a consequence of its broader binding profile, SOM230 is likely to find clinical utility in treating tumors resistant to SSTR-2-preferential analogs.
This work was supported by grants from Novartis Pharma and the Doris Factor Molecular Endocrinology Laboratory.
Abbreviations: PRL, Prolactin; RT, reverse transcriptase; SRIF, somatostatin; SSTR, somatostatin receptor.
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