The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion

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 IC(50) 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 alpha-subunit secretion from nonfunctioning pituitary adenomas by 46 +/- 18% ( P = 0.34). In contrast, octreotide inhibited GH, PRL, and alpha-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.