NK3R Mediates the EGF-Induced SLα Secretion and mRNA Expression in Grass Carp Pituitary.

Xiangfeng Qin,Guangfu Hu,Xiaoyun Zhou,Jingyi Jia,Cheng Ye,Qiongyao Hu,Shaohua Xu

doi:10.3390/ijms20010091

Xiangfeng Qin, Guangfu Hu + Show 5 more

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https://doi.org/10.3390/ijms20010091

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Abstract

Epidermal growth factor (EGF) is a potent regulator of cell function in many cell types. In mammals, the EGF/EGFR system played an important role in both pituitary physiology and pathology. However, it is not clear about the pituitary action of EGF in lower vertebrates. In this study, using grass carp as a model, we found that EGF could stimulate NK3R mRNA and protein expression through pituitary ErbB1 and ErbB2 coupled to MEK/ERK and PI3K/Akt/mTOR pathways. In addition, EGF could also induce pituitary somatolactin α (SLα) secretion and mRNA expression in a dose- and time-dependent manner in vivo and in vitro. The stimulatory actions of EGF on SLα mRNA expression were also mediated by PI3K/Akt/mTOR and MEK/ERK pathways coupled to ErbB1 and ErbB2 activation. Our previous study has reported that neurokinin B (NKB) could also induce SLα secretion and mRNA expression in carp pituitary cells. In the present study, interestingly, we found that EGF could significantly enhance NKB-induced SLα mRNA expression. Further studies found that NK3R antagonist SB222200 could block EGF-induced SLα mRNA expression, indicating an NK3R requirement. Furthermore, cAMP/PKA inhibitors and PLC/PKC inhibitors could both abolish EGF- and EGF+NKB-induced SLα mRNA expression, which further supported that EGF-induced SLα mRNA expression is NK3R dependent.

Highlights

Epidermal growth factor (EGF) is a member of EGF family that includes other EGF-like ligands, such as heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor α (TGF α) and betacellulin (BTC)
Previous studies have reported that ErbBs and its ligands are all abundantly expressed in pituitary corticotroph cells [9], and functional studies confirm a role of EGF/ErbB system in corticotroph proliferation and hormone secretion both in a direct and paracrine fashion [10]
Tissue distribution displayed that EGF, HB-EGFa, ErbB1a, ErbB1b, ErbB2a, ErbB2b and ErbB3b could all be detected in grass carp pituitary (Figure 1C)

Summary

Introduction

Epidermal growth factor (EGF) is a member of EGF family that includes other EGF-like ligands, such as heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor α (TGF α) and betacellulin (BTC). Previous studies have reported that ErbBs and its ligands are all abundantly expressed in pituitary corticotroph cells [9], and functional studies confirm a role of EGF/ErbB system in corticotroph proliferation and hormone secretion both in a direct and paracrine fashion [10]. ErbB and its ligands are detected in lacto-somatotroph cells and have a functional role in prolactin (PRL) regulation at both gene and protein levels [13,14,15], far, EGF has been shown to have little effect on growth hormone (GH) regulation [16]. EGF and ErbB are both distributed in the pituitary, but they do not have effects on follicle stimulating hormone β (FSHβ), LHβ and GH mRNA expression in primary cultured pituitary cells [17]. Little is known about the functional role of EGF in other pituitary hormone secretion and mRNA expression in teleost

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