title: The novel somatostatin ligand (SOM230) regulates human and rat anterior pituitary hormone secretion.
abstract: 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 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.
authors.affiliation: Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90048, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murray
authors.forename: Kiwon
authors.initials: K
authors.lastname: Kim
authors.forename: Song-Guang
authors.initials: SG
authors.lastname: Ren
authors.forename: Ian
authors.initials: I
authors.lastname: Lewis
authors.forename: Gisbert
authors.initials: G
authors.lastname: Weckbecker
authors.forename: Christian
authors.initials: C
authors.lastname: Bruns
authors.forename: Shlomo
authors.initials: S
authors.lastname: Melmed
mesh_terms: D000236:Adenoma; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D005333:Fetus; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D015282:Octreotide / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; C517782:pasireotide; C093733:somatostatin receptor 2; D015282:Octreotide