Ca²⁺ stores may regulate multiple components of the secretory pathway. We examined the roles of biochemically independent intracellular Ca²⁺ stores on acute and longterm growth hormone (GH) release, storage, and mRNA levels in goldfish somatotropes. Thapsigargin-evoked [Ca²⁺]_i signal amplitude was similar to the Ca²⁺ mobilizing agonist GnRH, but thapsigargin (2µM) did not acutely increase GH release, suggesting uncoupling between [Ca²⁺]_i and exocytosis. However, 2µM thapsigargin affected long-term secretory function. Thapsigargin-treated cells displayed a steady secretion of GH (2 h, 12h, 24h) which decreased GH content (12h, 24h), but not GH mRNA/production (24h). Contrasting the results with thapsigargin, activating the ryanodine receptor (RyR) with 1nM ryanodine transiently increased GH release (2h). Prolonged activation of RyR (24h) reduced GH release, contents and apparent production, without changing GH mRNA levels. Inhibiting RyR with 10µM ryanodine increased GH mRNA levels, production and storage (2h). Increasing [Ca²⁺]i independently of Ca²⁺ stores using 30mM KCl decreased GH mRNA. Collectively, these results suggest that parts of the secretory pathway can be controlled independently by function-specific Ca²⁺ stores.