Somatostatin and its type 2 receptor expression in the pregnant and labouring myometrium

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 labour (TL). SST mediates its effects by a family of G-protein-coupled receptors (SSTR1-5). Activation of SSTR2 facilitates the contractility of smooth muscles, including the human gut and non-pregnant pig uterus. We hypothesized that SST/SSTR2 play a role in labour contractions, both term and preterm. The expression and localization of SST/SSTR2 was studied in human, rat, and mouse pregnant and labouring uterine tissues. Rodents' uteri were collected throughout gestation, TL and preterm labour (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 to not-in-labour 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 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 signalling may play a role in the process of labour in humans.