Autocrine/paracrine regulation of somatolactin {alpha} production in carp pituitary cells by local release of somatolactin {alpha} and {beta}: functional role of Jak2/Stat5, PI3K/Akt and MAPK signaling cascades

Abstract

Pituitary hormones can act locally via autocrine/paracrine mechanisms to modulate pituitary functions, which represent an interesting aspect of pituitary regulation other than the traditional hypothalamic control and feedback signals from peripheral tissues. Somatolactin (SL), a member of the growth hormone/prolactin family, is a pleiotropic hormone with diverse functions in fish models, but its pituitary actions have not been previously examined. Recently, two SL isoforms, SLα and SLβ, have been cloned in grass carp. Based on the sequences obtained, recombinant proteins of grass carp SLα and SLβ with bioactivity in inducing pigment aggregation in carp melanophores were produced. In carp pituitary cells, SLα secretion and cellular content were elevated by static incubation with carp SLα and SLβ, respectively. These stimulatory actions occurred with a parallel raise in SLα mRNA levels with no significant changes in SLβ protein content and gene expression. In parallel experiments, SLα mRNA expression could be reduced by removing endogenous SLα and SLβ using immunoneutralization with the respective SL antisera. At the pituitary cell level, SLα 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 treatment could also trigger rapid phosphorylation of STAT5b, Akt, MEK1/2, Erk1/2, MKK3, and P38 MAPK. These results, as a whole, suggest that (i) SLα and SLβ produced locally in the carp pituitary can serve as novel autocrine/paracrine stimulators for SLα release and synthesis, and (ii) SLα production caused by SLα and SLβ stimulation probably are mediated by SLα gene expression via activation of the JAK2/STAT5, PI3K/Akt and MAPK signaling pathways.