Somatostatin and its type 2 receptor expression in the pregnant and laboring myometrium.

Abstract

Uterine contractility is regulated by the interaction of myogenic, neurogenic, and hormonal mechanisms. The hormonal peptide somatostatin (SST) is significantly increased in human plasma during late pregnancy and term labor (TL). SST mediates its effects by a family of G-protein-coupled receptors (SSTR1-5). Activation of somatostatin receptor type 2 (SSTR2) facilitates the contractility of smooth muscles, including the human gut and nonpregnant pig uterus. We hypothesized that SST/SSTR2 play a role in labor contractions, both term and preterm. The expression and localization of SST/SSTR2 were studied in human, rat, and mouse pregnant and laboring uterine tissues. Rodents' uteri were collected throughout gestation, TL, and preterm labor (PTL). Human myometrial biopsies were collected from TL and PTL women undergoing cesarean section. Human and rodent uterine tissues were fixed in formalin for immunohistochemistry (n = 4-7/group). Immunostaining of human and rodent' myometrium revealed stronger SSTR2 protein expression by myocytes and tissue macrophages during TL and PTL, as compared with not-in-labor patients or rodents. To examine the SST/SSTR2 mechanism, human monocytes were isolated from maternal peripheral blood and differentiated into macrophages. Primary human myocytes were isolated from the myometrium, cultured, and subjected to static mechanical stretch in vitro. Proteins were extracted and analyzed by immunoblotting, and the results indicate stretch-induced upregulation of SSTR2 in myocytes. Cell-conditioned media were analyzed by SST enzyme-linked immunosorbent assay (ELISA), indicating that human myocytes are a source of SST. When treated with exogenous SST, human myocytes induced contraction of a collagen gel. We conclude that SST/SSTR2 signaling may play a role in the process of labor in humans.NEW & NOTEWORTHY We show for the first time that somatostatin receptor type 2 (SSTR2) expression is upregulated in human and rodent myometrium during term and preterm labor. SSTR2 is expressed by myocytes and resident macrophages and is induced by mechanical stretch and inflammatory conditions. Human myocytes secrete somatostatin (SST), and its binding to SSTR2 enhances myocyte contractility in collagen gels, revealing a stretch- and inflammation-responsive SST-SSTR2 axis that promotes uterine contraction.