Regulation and action of early growth response 1 in bovine granulosa cells

Abstract

Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF-response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased <i>EGR1</i> and <i>EGR3</i> mRNA levels, whereas FGF18 increased only <i>EGR1</i> mRNA abundance. No mRNA encoding <i>EGR2</i> or <i>EGR4</i> was detected. Overexpression of EGR1 increased <i>EGR3</i> mRNA levels as well as the FGF-response genes <i>SPRY2</i>, <i>NR4A1</i> and <i>FOSL1</i> and also increased the phosphorylation of MAPK3/1. Knockdown of EGR3 did not alter the ability of FGF8b to stimulate <i>SPRY2</i> mRNA levels. These data demonstrate the regulation of <i>EGR1</i> and <i>EGR3</i> mRNA abundance by FGFs in granulosa cells and suggest that EGR1 is likely an upstream component of FGF signaling in granulosa cells.