Figure 11.

A working model of the mechanism of action of WNT5a in GCs. Left: canonical WNTs act in tandem with gonadotropin/PKA signaling in the GCs of growing follicles to stabilize CTNNB1 and CREB, resulting in the transcriptional activation of CTNNB1 and FSH/LH target genes. Right: WNT5a may antagonize canonical WNTs by competing for their receptor complex. The resultant disinhibition of GSK3β leads to the degradation of CTNNB1 and CREB, thereby antagonizing gonadotropin action. Whether GSK3β promotes CREB degradation through direct phosphorylation remains to be determined.