Calcium buffering activity of mitochondria controls basal growth hormone secretion and modulates specific neuropeptide signaling.
Goldfish somatotropes contain multiple functionally distinct classes of non-mitochondrial intracellular Ca(2+) stores. In this study, we investigated the role of mitochondrial Ca(2+) handling in the control of hormone secretion. Inhibition of mitochondrial Ca(2+) uptake with 10 microM ruthenium red (RR) and 10 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP) caused a small and reversible increase in cytosolic [Ca(2+)]. Despite relatively modest global Ca(2+) signals, RR and CCCP stimulated robust GH secretion under basal culture conditions. CCCP-stimulated hormone release was abolished in cells pre-incubated with 50 microM BAPTA-AM, suggesting that elevations in cytosolic [Ca(2+)] mediate this release of GH. Both caffeine-sensitive intracellular Ca(2+) stores and L-type Ca(2+) channels can be the source of the Ca(2+) buffered by mitochondria in somatotropes. The stimulatory effect of RR on caffeine-stimulated GH release was enhanced dramatically in the presence of ryanodine, pointing to a complex interaction between these three Ca(2+) stores. Inhibition of mitochondrial Ca(2+) uptake with RR augmented GH release evoked by only one of the two endogenous gonadotropin-releasing hormones. Thus, we provide the first evidence that mitochondrial Ca(2+) buffering is differentially involved in specific agonist Ca(2+) signaling pathways and plays an important role in the control of basal GH release.
Johnson
James D
JD
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Chang
John P
JP
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D006054:Goldfish; D013006:Growth Hormone / Q000378:metabolism*; D006706:Homeostasis; D008928:Mitochondria / Q000378:metabolism*; D009570:Nitriles; D010902:Pituitary Gland / Q000166:cytology; D012430:Ruthenium Red; D015398:Signal Transduction
D002021:Buffers; D009570:Nitriles; D012430:Ruthenium Red; C100076:mesoxalonitrile; D013006:Growth Hormone; D002118:Calcium