Impact of growth hormone-releasing hormone (GHRH) antagonist on Decidual stromal cell growth and apoptosis in vitro

Biol Reprod. 2021 Nov 18:ioab214. doi: 10.1093/biolre/ioab214. Online ahead of print.ABSTRACTEndometrial stromal cells remodeling is critical during human pregnancy. GHRH and its functional receptor have been shown to be expressed in gynecological cancer cells and eutopic endometrial stromal cells. Recent studies have demonstrated the potential clinical uses of antagonists of GHRH as effective antitumor agents because of its directly antagonistic effect on the locally produced GHRH in gynecological tumors. However, the impact of GHRH antagonists on normal endometrial stromal cell growth remained to be elucidated. The aim of this study was to investigate the effect of a GHRH antagonist (JMR-132) on cell proliferation and apoptosis of human decidual stromal cells and the underlying molecular mechanisms. Our results showed that GHRH and the splice variant 1 (SV1) of GHRH receptor (GHRH-R SV1) are expressed in human decidual stromal cells isolated from the decidual tissues of early pregnant women receiving surgical abortion. In addition, treatment of stroma cells with JMR-132 induced cell apoptosis with increasing cleaved caspase-3 and caspase-9 activities, and decrease cell viability in a time- and dose-dependent manner. Using a dual inhibition approach (pharmacological inhibitors and siRNA-mediated knockdown), we showed that JMR-132-induced activation of apoptotic signals are mediated by the activation of ERK1/2 and JNK signaling pathways and the subsequent upregulation of GADD...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research