title: Agonist-specific Ca2+ signaling systems, composed of multiple intracellular Ca2+ stores, regulate gonadotropin secretion.
abstract: Ca2+ signals regulate many cellular functions, including hormone secretion. Agonist-specific Ca2+ signaling may arise from the differential mobilization of multiple Ca2+ stores. Although they act through the same receptor subtype, two gonadotropin-releasing hormones (sGnRH and cGnRH-II) generate quantifiably different Ca2+ signals in goldfish gonadotropes, suggesting that their Ca2+-dependent signaling cascades may differ. We combined electrophysiology, Ca2+ imaging, and radioimmunoassay detection of gonadotropin (GTH-II) secretion to determine the role of intracellular Ca2+ stores in GnRH-stimulated exocytosis. Our findings suggest that voltage-gated Ca2+ channels do not mediate acute GnRH-signaling. Instead, both sGnRH- and cGnRH-II-stimulated GTH-II releases are dependent on Ca2+ 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 Ca2+ availability increase GTH-II release by mobilizing Ca2+ stores. Our results are the first to suggest that several classes of intracellular Ca2+ stores differentially participate in agonist signaling and homeostasis in gonadotropes.
authors.affiliation: Department of Biological Sciences, Biological Sciences Building, University of Alberta, CW 405, Edmonton, Alberta, Canada T6G 2E9.
authors.forename: J D
authors.initials: JD
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: VanGoor
authors.forename: R M
authors.initials: RM
authors.lastname: Jobin
authors.forename: C J
authors.initials: CJ
authors.lastname: Wong
authors.forename: J I
authors.initials: JI
authors.lastname: Goldberg
authors.forename: J P
authors.initials: JP
authors.lastname: Chang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002614:Chelating Agents; D003952:Diagnostic Imaging; D016257:Fura-2; D006054:Goldfish; D007987:Gonadotropin-Releasing Hormone / Q000187:drug effects / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000819:agonists* / Q000378:metabolism; D006706:Homeostasis; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology; D011863:Radioimmunoassay
chemical_list: D015220:Calcium Channels; D002614:Chelating Agents; D006065:Gonadotropins, Pituitary; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium; D016257:Fura-2