Jiang Q, Wong AO. Signal transduction mechanisms for autocrine/paracrine regulation of somatolactin-␣ secretion and synthesis in carp pituitary cells by somatolactin-␣ and -. Am J Physiol Endocrinol Metab 304: E176 -E186, 2013. First published November 27, 2012 doi:10.1152/ajpendo.00455.2012.-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, SL␣ and SL, have been cloned in grass carp. Based on the sequences obtained, recombinant proteins of carp SL␣ and SL with similar bioactivity in inducing pigment aggregation in carp melanophores were produced. In carp pituitary cells, SL␣ secretion and cell content were elevated by static incubation with recombinant carp SL␣ and SL, respectively. These stimulatory actions occurred with a parallel rise in SL␣ mRNA level with no changes in SL secretion, cell content, and gene expression. In contrast, SL␣ mRNA expression could be reduced by removing endogenous SL␣ and SL with immunoneutralization. At the pituitary cell level, SL␣ release, cell content, and mRNA expression induced by carp SL␣ and SL could be blocked by inhibiting JAK2/STAT5, PI3K/Akt, MEK1/2, and p38 MAPK, respectively. Furthermore, SL␣ and SL induction also triggered rapid phosphorylation of STAT5, Akt, MEK1/2, ERK1/2, MKK3/6, and p38 MAPK. These results suggest that 1) SL␣ and SL produced locally in the carp pituitary can serve as novel autocrine/ paracrine stimulators for SL␣ secretion and synthesis and 2) SL␣ production induced by local release of SL␣ and SL probably are mediated by the JAK2/STAT5, PI3K/Akt, and MAPK signaling pathways.somatolactin; autocrine/paracrine regulation; signal transduction; pituitary; grass carp SOMATOLACTIN, a member of the growth hormone (GH)/prolactin (PRL) family, is originally identified in the pars intermedia of the Atlantic cod (30). Based on comparative synteny and sequence homology analysis, it is commonly accepted that SL is derived from the ancestral GH during the early phase of gnathostome evolution by gene duplication (20). Two SL isoforms, SL␣ and SL, have been report in bony fish (16,52). Similar to GH and PRL, SL is a member of the class I cytokines with the typical feature of four ␣-helixes arranged in an up-up-down-down topography (16). To date, SL has been associated with diverse functions in fish models, including reproduction (29, 36), stress (21), lipid metabolism (40), background adaptation (53, 55), phosphate transport (25), melanosome aggregation (28, 54), and immune responses (4). Although most of the above-mentioned functions attributed to SL were based on correlational studies, the functional role of SL in color presentation has been unequivocally demo...