The importance of CTGF regulation by FSH, IGF1, and estradiol in bovine granulosa cells.

During the ovarian follicle growth of monovulatory species, the dominant follicle is characterized by a greater capacity for estradiol (E2) production mainly due to an increased granulosa cell (GC) CYP19A1 transcription level. The connective tissue growth factor (CTGF) has emerged as a potential novel and important player in the modulation of CYP19A1 expression in this cell type. To gain insight into how CTGF is regulated in GC and to better understand its role during GC differentiation into a more estrogenic phenotype, we have performed in the present study a series of experiments employing bovine GC cultures. We demonstrate herein that CTGF mRNA levels are downregulated by insulin-like growth factor 1 (IGF1) and E2, two critical regulators of follicle dominance establishment in vivo. In turn, CTGF suppresses CYP19A1 mRNA levels in bovine GC both in the presence or absence of FSH or IGF1, through a mechanism that seems to involve altering the phosphorylation pattern of AKT and the modulation of NR5A2, a critical transcription factor of CYP19A1. Overall, our study indicates that CTGF downregulation in GC may represent a critical step for enabling the increased CYP19A1 transcriptional activity of the dominant follicle in cattle.