Secretoneurin stimulates the production and release of luteinizing hormone in mouse LβT2 gonadotropin cells

Secretoneurin (SN) is a functional secretogranin II (SgII)-derived peptide that stimulates luteinizing hormone (LH) production and its release in the goldfish. However, the effects of SN on the pituitary of mammalian species and the underlying mechanisms remain poorly understood. To study SN in mammals, we adopted the mouse LβT2 gonadotropin cell line that has characteristics consistent with normal pituitary gonadotrophs. Using radioimmunoassay and real-time RT-PCR, we demonstrated that static treatment with SN induced a significant increment of LH release and production in LβT2 cells in vitro. We found that GnRH increased cellular SgII mRNA level and total SN-immunoreactive protein release into the culture medium. We also report that SN activated the extracellular signal-regulated kinases (ERK) in either 10-min acute stimulation or 3-h chronic treatment. The SN-induced ERK activation was significantly blocked by pharmacological inhibition of MAPK kinase (MEK) with PD-98059 and protein kinase C (PKC) with bisindolylmaleimide. SN also increased the total cyclic adenosine monophosphate (cAMP) levels similarly to GnRH. However, SN did not activate the GnRH receptor. These data indicate that SN activates the protein kinase A (PKA) and cAMP-induced ERK signaling pathways in the LH-secreting mouse LβT2 pituitary cell line.