IGF Potentiation of Nkb- and Nkbrp-Induced Somatolactin α Gene Expression Via up-Regulation of NK3 Receptor Expression and Functional Crosstalk in Post-Receptor Signaling in Carp Pituitary Cells

Presentation Number: SAT 436
Date of Presentation: April 1st, 2017

Guangfu Hu, Mu-Lan He, Wendy K.W. Ko and Anderson O L Wong*
University of Hong Kong, Hong Kong, China

Abstract

Neurokinin B (NKB)/NK3 receptor (NK3R) system has recently emerged as a key component of reproductive functions in mammals. In our recent study, the carp TAC3 gene products, namely NKB and NKB-related peptide (NKBRP), were shown to be novel stimulators for somatolactin α (SLα) synthesis and secretion via NK3R activation in grass carp pituitary cells. In this study, we seek to examine if NK3R expression can serve as a regulatory target in the carp pituitary and contribute to NKB/NKBRP interactions with other SLα regulators. As a first step, grass carp NK3R was cloned and confirmed to be expressed at high level in the carp pituitary. Functional expression of carp NK3R in HEK293 cells also revealed that the newly cloned receptor exhibited ligand binding selectivity and post-receptor signaling highly comparable to its mammalian counterpart. In carp pituitary cells, NK3R mRNA expression could be elevated by IGF1 and IGF2 via IGF1 receptor coupled to PI3K/Akt and MAPK pathways. Interestingly, IGF1/2 co-treatment was found to markedly enhance NKB/NKBRP-induced SLα mRNA expression and the potentiating effect was dependent on NK3R expression and activation of cAMP/PKA, PLC/IP3/PKC, Ca2+/CaM/CaMK-II cascades. Besides, SLα mRNA expression mediated by cAMP/PKA signaling but not PKC/Ca2+-dependent mechanisms could be potentiated by IGF co-treatment and IGF1-induced Akt phosphorylation but not MEK1/2, ERK1/2 and P38 MAPK phosphorylation was notably enhanced by NK3R activation. These results, taken together, suggest that the synergistic effect on SLα gene expression by IGFs and TAC3 gene products was mediated by NK3R up-regulation and functional crosstalk of post-receptor signaling in the carp pituitary.

 

Nothing to Disclose: GH, MLH, WKWK, AOLW