Kisspeptin induction of somatolactin- release in goldfish pituitary cells: functional role of cAMP/PKA-, PLC/PKC-, and Ca /calmodulin-dependent cascades

Jiang Q, He M, Ko WK, Wong AO. Kisspeptin induction of somatolactinrelease in goldfish pituitary cells: functional role of cAMP/PKA-, PLC/PKC-, and Ca /calmodulin-dependent cascades. Am J Physiol Endocrinol Metab 307: E872–E884, 2014. First published September 2, 2014; doi:10.1152/ajpendo.00321.2014.— Although the importance of kisspeptin in the pituitary is firmly established, the signaling mechanisms for the pituitary actions of kisspeptin are still largely unknown. Somatolactin (SL), a member of the growth hormone (GH)/prolactin (PRL) family, is a pituitary hormone with pleiotropic functions in fish, but its regulation by kisspeptin has not been examined. To investigate the functional role of kisspeptin in SL regulation, expression of two paralogues of goldfish Kiss1 receptors (Kiss1ra and Kiss1rb) were confirmed in immunoidentified SL but not SL cells isolated by RT-PCR coupled with laser capture microdissection. In goldfish pituitary cells prepared from neurointermediate lobe (NIL), synthetic goldfish Kiss decapeptides (gKiss1-10 and gKiss2-10) could increase SL release. Consistent with the lack of Kiss1r expression in SL cells, SL release was not altered by kisspeptin stimulation. In parallel experiments, goldfish gKiss1-10 could elevate cyclic adenosine monophosphate (cAMP) production, upregulate protein kinase A (PKA) and protein kinase C (PKC) activities, and trigger a rapid rise in intracellular Ca levels in goldfish NIL cells. Using a pharmacological approach, cAMP/PKA and phospholipase C (PLC)/PKC pathways and subsequent activation of Ca /calmodulin (CaM)-dependent cascades were shown to be involved in SL release induced by gKiss1-10. Apparently, the Ca -dependent cascades were triggered by extracellular Ca entry via voltage-sensitive Ca channels and mobilization of inositol trisphosphate-sensitive intracellular Ca stores. Our results demonstrate that gKiss1-10 can act directly at the pituitary level to trigger SL release via a complex network of post-receptor signaling mechanisms.