Agonist-specific Ca 2+ signaling systems, composed of multiple intracellular Ca 2+ stores, regulate gonadotropin secretion

Abstract

Ca 2+ signals regulate many cellular functions, including hormone secretion. Agonist-specific Ca 2+ signaling may arise from the differential mobilization of multiple Ca 2+ stores. Although they act through the same receptor subtype, two gonadotropin-releasing hormones (sGnRH and cGnRH-II) generate quantifiably different Ca 2+ signals in goldfish gonadotropes, suggesting that their Ca 2+-dependent signaling cascades may differ. We combined electrophysiology, Ca 2+ imaging, and radioimmunoassay detection of gonadotropin (GTH-II) secretion to determine the role of intracellular Ca 2+ stores in GnRH-stimulated exocytosis. Our findings suggest that voltage-gated Ca 2+ channels do not mediate acute GnRH-signaling. Instead, both sGnRH- and cGnRH-II-stimulated GTH-II releases are dependent on Ca 2+ mobilized from TMB–8/CPA-sensitive compartments. However, sGnRH, but not cGnRH-II, utilizes intracellular stores sensitive to caffeine and xestospongin C. We also identified a homeostatic mechanism where reduced extracellular Ca 2+ availability increase GTH-II release by mobilizing Ca 2+ stores. Our results are the first to suggest that several classes of intracellular Ca 2+ stores differentially participate in agonist signaling and homeostasis in gonadotropes.