Subplasmalemmal hydrogen peroxide triggers calcium influx in gonadotropes

摘要: Gonadotropin-releasing hormone (GnRH) stimulation of its eponymous receptor on the surface endocrine anterior pituitary gonadotrope cells (gonadotropes) initiates multiple signaling cascades that culminate in secretion luteinizing and follicle-stimulating hormones, which have critical roles fertility reproduction. Enhanced biosynthesis, a necessary event for ovulation, requires pathway characterized by calcium influx through L-type channels subsequent activation mitogen-activated protein kinase extracellular signal-regulated (ERK). We previously reported highly localized subplasmalemmal microdomains produced (calcium sparklets) play an essential part GnRH-dependent ERK activation. Similar to calcium, reactive oxygen species (ROS) are ubiquitous intracellular molecules whose subcellular localization determines their specificity. To investigate potential influence oxidant gonadotropes, here we examined impact ROS generation channel function. Total internal reflection fluorescence (TIRF) microscopy revealed GnRH induces spatially restricted sites gonadotrope-derived αT3-1 cells. Furthermore, required hydrogen peroxide these primary mouse gonadotropes. NADPH oxidase mitochondrial were each GnRH-mediated channels. Congruently, increased oxidation within mitochondria, activity correlated strongly with presence adjacent mitochondria. Collectively, our results provide compelling evidence mitochondria-derived fundamental role