Abstract

Epidermal growth factor (EGF) is a member of the EGF-like ligands family, which plays a vital role in cell proliferation, differentiation, and folliculogenesis through binding with EGF receptors, including ErbB1 (EGFR/HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4). In mammals, many functional roles of EGF have been reported in the ovaries and breasts. However, little is known about the functions of EGF in the pituitary, especially in teleost. In this study, using grass carp pituitary cells as the model, we try to examine the direct pituitary actions of EGF in teleost. Firstly, transcriptomic analysis showed that 599 different expressed genes (DEGs) between the control and EGF-treatment group were mainly involved in cell proliferation, cell migration, signal transduction, and transcriptional regulation. Then, we further confirmed that EGF could significantly induceUTS1,EGR1, andMMP13mRNA expression in a time-and dose-dependent manner. The stimulatory actions of EGF onUTS1andEGR1mRNA expression were mediated by the MEK1/2/ERK1/2and PI3K/AKT/mTOR pathways coupled with both ErbB1 and ErbB2 in grass carp pituitary cells. The receptor specificity and signal transductions for the corresponding responses onMMP13mRNA expression were also similar, except that the ErbB2 and PI3K/AKT/mTOR pathway were not involved. As we know,MMP13could release EGF from HB-EGF. Interestingly, our data also showed that the MMPs inhibitor BB94 could suppress EGF-inducedUTS1andEGR1mRNA expression. These results, taken together, suggest that the stimulatory actions of EGF onUTS1andEGR1mRNA expression could be enhanced by EGF-inducedMMP13expression in the pituitary.Keywords:signal transduction;pituitary cells;pharmacological test;ErbB;grass carp