Activated receptor tyrosine kinases in granulosa cells of ovulating follicles in mice

Abstract

Successful ovulation requires the actions of gonadotropins along with those mediated by growth factors binding to their receptor tyrosine kinases (RTKs). There are several growth factors such as epidermal growth factor family ligands and interleukins that play a role during ovulation initiated by the preovulatory surge of luteinizing hormone (LH). The aim of this project was to analyze growth factor signaling pathways induced by LH in mouse granulosa cells. Immature female mice were treated with equine chorionic gonadotropin (eCG) followed 48 hr later by human chorionic gonadotropin (hCG) to induce follicular growth and ovulation. We performed protein array analysis where we identified higher phosphorylation of insulin-like growth factor 1 receptor (IGF1R), the fibroblast growth factor receptor 2 (FGFR2) and ephrin receptor B1 (EPHB1) in granulosa cells at 4 hr post-hCG compared to 0 hr hCG (p < 0.05). We report both a significant increase in transcript abundance (p < 0.05) and the phosphorylation level (p < 0.05) of the IGF1R in granulosa cells at hCG4h. The mRNA abundance of the Fgfr2 and Ephb1 receptors remained unaltered upon hCG treatment. Nonetheless, transcript abundance of the fibroblast growth factor 2 (Fgf2) ligand was elevated at hCG4h (p < 0.01). Based on these results we conclude that the preovulatory LH surge activates signaling pathways of IGF1R through increase in the expression of the Igf1r gene in granulosa cells of ovulating follicles in mice. The LH surge also appears to activate FGFR2 IIIc and EPHB1 signaling, although further investigation is required.

Tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K/AKT signaling

“…SHP2 may also regulate the AKT signaling pathway through some RTKs in GCs, e.g. IGF1 receptor showed a significantly increased transcript abundance and phosphorylation level in GCs treated with equine chorionic gonadotropin ( Schuermann et al., 2018 ). In addition, through its phosphatase activity, SHP2 can positively or negatively regulate various cellular signaling pathways, such as the Ras/MAPK, Nrf2/NF-κB, and JAK/STAT signaling pathways.…”

Repairing effects of glucosamine sulfate in combination with etoricoxib on articular cartilages of patients with knee osteoarthritis

“…TGF-β is a crucial cartilage repair factor, which can maintain the normal structure and function of articular cartilage. The higher the level of TGF-β is, the more favorable the repair of knee osteoarticular injury will be [17]. IGF-1 can accelerate the proliferation of chondrocytes and the formation of chondrocyte colonies by stimulating chondrocytes to synthesize protein polysaccharides and collagen type II.…”

Repairing effects of glucosamine sulfate in combination with etoricoxib on articular cartilages of patients with knee osteoarthritis

“…TGF-β is a crucial cartilage repair factor, which can maintain the normal structure and function of articular cartilage. The higher the level of TGF-β is, the more favorable the repair of knee osteoarticular injury will be [13]. IGF-1 can accelerate the proliferation of chondrocytes and the formation of chondrocyte colonies by stimulating chondrocytes to synthesize protein polysaccharides and collagen type II.…”