Serotonin interferes with Ca2+ and PKC signaling to reduce gonadotropin-releasing hormone-stimulated GH secretion in goldfish pituitary cells.
In goldfish, two endogenous gonadotropin-releasing hormones (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), are thought to stimulate growth hormone (GH) release via protein kinase C (PKC) and subsequent increases in intracellular Ca(2+) levels ([Ca(2+)](i)). In contrast, the signaling mechanism for serotonin (5-HT) inhibition of GH secretion is still unknown. In this study, whether 5-HT inhibits GH release by actions at sites along the PKC and Ca(2+) signal transduction pathways leading to hormone release were examined in primary cultures of goldfish pituitary cells. Under static incubation and column perifusion conditions, 5-HT reduced basal, as well as sGnRH- and cGnRH-II-stimulated, GH secretion. 5-HT also suppressed GH responses to two PKC activators but had no effect on the GH-releasing action of the Ca(2+) ionophore ionomycin. Ca(2+)-imaging studies with identified somatotropes revealed that 5-HT did not alter basal [Ca(2+)](i) but attenuated the magnitude of the [Ca(2+)](i) responses to the two GnRHs. Prior treatment with 5-HT and cGnRH-II reduced the magnitude of the [Ca(2+)](i) responses induced by depolarizing levels of K(+). Similar inhibition, however, was not observed with prior treatment of 5-HT and sGnRH. These results suggest that 5-HT, by direct actions at the somatotrope level, interferes with PKC and Ca(2+) signaling pathways to reduce the GH-releasing effect of GnRH. 5-HT action may occur at the level of PKC activation or its downstream signaling events prior to the subsequent rise in [Ca(2+)](i.). The differential Ca(2+) responses by depolarizing doses of K(+) is consistent with our previous findings that sGnRH and cGnRH-II are coupled to overlapping and yet distinct Ca(2+)-dependent mechanisms.
Yu
Yi
Y
Department of Biological Sciences, CW-405, Biological Science Building, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
Wong
Anderson O L
AO
Chang
John P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006054:Goldfish; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D012701:Serotonin; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone; D011493:Protein Kinase C; D002118:Calcium