Signal transduction mechanisms for autocrine/paracrine regulation of somatolactin-α secretion and synthesis in carp pituitary cells by somatolactin-α and -β

Abstract

Pituitary hormones can act locally via autocrine/paracrine mechanisms to modulate pituitary functions, which represents an interesting aspect of pituitary regulation other than the traditional hypothalamic input and feedback signals from the periphery. Somatolactin, a member of the growth hormone (GH)/prolactin (PL) family, is a pleiotropic hormone with diverse functions, but its pituitary actions are still unknown. Recently, two SL isoforms, SLα and SLβ, have been cloned in grass carp. Based on the sequences obtained, recombinant proteins of carp SLα and SLβ with similar bioactivity in inducing pigment aggregation in carp melanophores were produced. In carp pituitary cells, SLα secretion and cell content were elevated by static incubation with recombinant carp SLα and SLβ, respectively. These stimulatory actions occurred with a parallel rise in SLα mRNA level with no changes in SLβ secretion, cell content, and gene expression. In contrast, SLα mRNA expression could be reduced by removing endogenous SLα and SLβ with immunoneutralization. At the pituitary cell level, SLα release, cell content, and mRNA expression induced by carp SLα and SLβ could be blocked by inhibiting JAK2/STAT5, PI3K/Akt, MEK1/2, and p38 MAPK, respectively. Furthermore, SLα and SLβ induction also triggered rapid phosphorylation of STAT5, Akt, MEK1/2, ERK1/2, MKK3/6, and p38 MAPK. These results suggest that 1) SLα and SLβ produced locally in the carp pituitary can serve as novel autocrine/paracrine stimulators for SLα secretion and synthesis and 2) SLα production induced by local release of SLα and SLβ probably are mediated by the JAK2/STAT5, PI3K/Akt, and MAPK signaling pathways.