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 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.
Murray
Robert D
RD
Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90048, USA.
Kim
Kiwon
K
Ren
Song-Guang
SG
Lewis
Ian
I
Weckbecker
Gisbert
G
Bruns
Christian
C
Melmed
Shlomo
S
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
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; C517782:pasireotide; C093733:somatostatin receptor 2; D015282:Octreotide