Human chorionic gonadotropin-dependent up-regulation of epiregulin and amphiregulin in equine and bovine follicles during the ovulatory process

Molecular characterization of a disintegrin and metalloprotease-17 (ADAM17) in granulosa cells of bovine preovulatory follicles

“…In the present study, results showed the ability of ERK1/2 inhibitor U0126 to suppress FSK-dependent ADAM17 promoter activity and transcript expression in bovine granulosa cells, in keeping with similar inhibitory effects observed on bovine ADAMTS1 and RGS2 gene expression (Sayasith et al, 2013a(Sayasith et al, , 2014, suggesting that ERK1/2 acts downstream of the PKA signaling pathway (Seger et al, 2001). Previous studies revealed the upregulation of AREG and EREG (ADAM17 substrates) in bovine preovulatory follicles after hCG stimulation in vivo and in bovine granulosa cells stimulated with FSK in vitro (Sayasith et al, 2013b).…”

“…Interestingly, recent studies revealed that levels of ADAM17 mRNA in primary cultures of bovine granulosa cells were unaffected by LH stimulation alone, but transiently increased by a co-treatment with LH and angiotensin-2 (Portela et al, 2011). In the present study, FSK was used as an agonist to avoid issues related to variations in LH receptor expression in bovine granulosa cells maintained in cultures, and because of its ability to reproduce in vitro the gonadotropindependent induction of ovulatory genes observed in vivo in bovine and rodent preovulatory follicles (Liu et al, 1999;Panigone et al, 2008;Sayasith et al, 2004Sayasith et al, , 2013aSayasith et al, , 2013bShimada et al, 2006). Results showed that the FSK-dependent up-regulation of ADAM17 mRNA in granulosa cells in vitro was similar to that observed after hCG treatment in vivo, thus validating the use of this cell culture system for further investigating the molecular control of ADAM17 gene expression in bovine ovarian cells.…”

“…A recent study using a developmental series of equine preovulatory follicles collected before and after hCG treatment showed that levels of follicular ADAM17 mRNA were high prior to hCG and remained unchanged throughout the ovulatory process (Sayasith et al, 2013b). In contrast, using a similar model (hCG-dependent induction of ovulation), the present study documents a different pattern of expression in bovine preovulatory follicles, as levels of ADAM17 transcripts were very low prior to hCG (0 h), markedly up-regulated 6-12 h post-hCG, and returned to low baseline levels at 24 h Fig.…”

“…Indeed, amphiregulin (AREG) and epiregulin (EREG) are two major EGFR ligands that are structurally and functionally related (Harris et al, 2003). The expression of both genes is rapidly induced by LH or human chorionic gonadotropin (hCG) in mural granulosa cells of preovulatory follicles (Ashkenazi et al, 2005;Park et al, 2004;Sayasith et al, 2013b). As cumulus cells express EGFR, and its activation by binding with AREG and EREG was required for successful ovulation (Ashkenazi et al, 2005;Orly et al, 1994;Panigone et al, 2008;Park et al, 2004), LH-induced AREG and EREG in mural granulosa cells are thought to act as endogenous messengers to diffuse signals throughout the follicles prior to ovulation (Conti et al, 2006;Panigone et al, 2008).…”

Regulation of ovulatory genes in bovine granulosa cells: lessons from siRNA silencing of PTGS2

“…For instance, explants of preovulatory mice follicles treated with LH and AG14780 (EGFR kinase inhibitor) showed no expression of Ptgs2 (Ashkenazi et al 2005). Similarly, reduced PTGS2 was noted when bovine GCs that were treated with the FRS, an adenylyl cyclase activator and an inhibitor of EGFR tyrosine kinase activity (Sayasith et al 2013). In a recent study, EGFR knockdown has resulted in reduced expression of PTGS2 and decreased PGE2 (Fang et al 2013).…”