Secretoneurin is a Neuropeptide Regulating Luteinizing Hormone Release from Pituitary Gonadotrophs

Secretoneurin (SN) is a major functional peptide derived from the secretogranin II (SgII) precursor, one of granin family members. Our previous studies revealed that SN had a stimulatory action on luteinizing hormone (LH) secretion from goldfish pituitary in vivo and in vitro. In my PhD thesis, I isolated and identified free SN peptide in goldfish brain and pituitary by using reversed phase HPLC and western blots. Immunocytochemical localization showed that SN immunoreactivity (IR) was found within magnocellular neurons of the hypothalamic nucleus preopticus, prolactin producing lactotrophs in rostral pars distalis (RPD) of the pituitary and nerve fibres in pituitary neurointennediate lobe (NIL). These studies indicated the production of SN in goldfish brain and pituitary. I furthermore explored SN production under the regulation of hypothalamic gonadotropin releasing hormone (GnRH). Treatment of dispersed goldfish pituitary cells in vitro with GnRH increased both gene and protein expression of SgII and SgII-derived peptides which were significantly associated with that of prolactin. In vitro treatment with SN stimulated LH release from dispersed goldfish pituitary cells. Immunoneutralization experiments indicated that pituitary-sourced endogenous SN not only plays a paracrine role but also acts as a potential transduction factor to mediate GnRH-induced LH release in goldfish pituitary. In mouse LbetaT2 gonadotrophs, SN is able to up-regulate both LH secretion and the mRNA levels of multiple gonadotropin subunits. In LbetaT2 cells, SN also activates a mitogen-activated protein kinase (MAPK) cascade leading to phosphorylation of extracellular signal-regulated kinase (ERK). Further studies should focus on the isolation and localization of SN receptors in pituitary to expand the hypothesis that SN is a newly-identified hormone in the neuroendocrine system.