Function-specific calcium stores selectively regulate growth hormone secretion, storage, and mRNA level

Abstract

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

A Gonadotropin‐Releasing Hormone Insensitive, Thapsigargin‐Sensitive Ca2+ Store Reduces Basal Gonadotropin Exocytosis and Gene Expression: Comparison with Agonist‐Sensitive Ca2+ Stores

“…In the present study, the acute inhibitory GTH‐II release response is specific to Tg‐sensitive Ca 2+ stores, since it is not mimicked by other treatments that affect goldfish gonadotrope Ca 2+ stores (Ry, cyclopiazonic acid) (22, 23). In addition, the growth hormone release response measured under identical conditions is not inhibited by Tg (47, 48), suggesting cell specificity. To our knowledge, this is the first demonstration of an intracellular Ca 2+ store that specifically blocks basal hormone release when perturbed, without affecting agonist‐evoked exocytosis.…”

PKC and ERK are differentially involved in gonadotropin-releasing hormone-induced growth hormone gene expression in the goldfish pituitary

“…Our results indicate that conventional and novel PKCs are not likely to be involved in GnRH-stimulated GH gene expression, suggesting that the signal transduction pathways mediating GnRH effects on GH gene expression are different from those regulating GH secretion in the goldfish pituitary. Indeed, previous studies in goldfish examining the regulation of GH secretion, storage, and gene expression by multiple intracellular Ca 2ϩ stores appear to support the hypothesis that secretion and gene expression can be independently controlled by function-specific signaling (26).…”

Seasonal effects of GnIH on basal and GnRH-induced goldfish somatotrope functions

“…Additionally, results from our previous investigations have indicated that gGnIH is also able to uncouple lhb mRNA expression and LH secretion . Post-receptor signaling mechanisms mediating differential actions of gGnIH on GH release and gene expression remain to be studied in the future, but differential use of pharmacologically distinct intracellular Ca 2C pools, protein kinase C, and ERK have been indicated to be factors enabling selective modulation of GH secretion and synthesis in goldfish (Johnson et al 2002.…”