Exogenous Secreted Frizzled-Related Protein-4 Modulates Steroidogenesis of Rat ‎Granulosa Cells Through Wnt/Bcatenin and PI3K/AKT Signaling Pathways‎

It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis.
GCs were firstly stimulated with Follicle-Stimulating Hormone (FSH) named as FSH-primed cells then were treated with luteinizing hormone (LH). Then estradiol (E2) and progesterone (P4) production levels were assessed in the absence or presence of rhSFRP-4 treatment. The expression levels of activated -catenin, pAKTser473, pGSK3ser9 were assessed by western blot or immuno-fluoresence.
In the presence of rhSFRP-4, there was 38% decreased E2 levels compared to untreated FSH-primed cells (p Taken together, our results showed that rhSFRP-4 could directly induce terminal differentiation in GCs via the modulation of β-catenin and PKB/AKT pathways and that it does so in a dose-dependent manner.