Abstract

Abstract Disclosure: C. Ye: None. X. Qin: None. M. He: None. A.O. Wong: None. Phoenixin (PNX), a novel peptide identified by bioinformatics, is known to have pleiotropic functions mediated by its receptor GPR173. At present, very little is known for PNX regulation and the intracellular signaling for PNX expression is still unclear. Recently, PNX and GPR173 were cloned in grass carp and found to be co-expressed in carp lactotrophs. In carp pituitary cells, PNX was also confirmed to be a novel autocrine/paracrine factor maintaining/stimulating prolactin (PRL) synthesis & secretion. To unveil the functional role of PNX in PRL regulation, a systematic screening of >40 neuroendocrine factors/local growth factors was conducted in the same cell model to look for regulators with modulatory functions for both PNX and PRL in carp pituitary. Based on our study, IGF-I & -II were shown to elevate PNX mRNA level with parallel rise in PRL gene expression in carp pituitary cells whereas the opposite was true for the functional agonist of LH, namely hCG. In parallel experiment, PRL mRNA expression induced by IGF-I was negated by removing endogenous PNX using immunoneutralization with PNX antiserum. Besides, hCG inhibition on PNX & PRL gene expression could be mimicked by parallel treatment of LH but not FSH, whereas removal of endogenous LH by LH antiserum immunoneutralization could lead to the opposite effects. Of note, hCG co-treatment not only attenuated the PNX and PRL responses induced by IGF-I but also triggered notable suppression of IGF-I receptor (IGF1R) gene expression at pituitary cell level. In our study, IGF1R & insulin receptor (InsR) expressed in carp pituitary cells were both activated by IGF-I treatment, but IGF-I induced PNX and PRL mRNA expression could be blocked only by the inactivators for IGF1R but not InsR. Using a pharmacological approach, the gene expression of PNX and PRL induced by IGF-I was confirmed to be mediated through the PI3K/Akt and MEK1/2/ERK1/2 but not P38MAPK pathways. Our findings, as a whole, suggest that (i) IGF signals can induce PRL gene expression in carp pituitary via IGF1R coupled to PI3K/Akt & MAPK cascades and this stimulatory effect is mediated via local production of PNX, and (ii) LH released in the pituitary can act locally to inhibit both basal & IGF-induced PRL expression and these inhibitory actions are mediated by blocking pituitary expression of PNX & IGF1R. Presentation: Friday, June 16, 2023

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