Abstract
Matrix metalloproteinases (MMP) are key enzymes involved in tissue remodeling. Within the ovary, they are believed to play a major role in ovulation, and have been linked to follicle atresia. To gain insight into the regulation of MMPs, we measured the effect of hormones and growth factors on MMP2 and MMP9 mRNA levels in non-luteinizing granulosa cells in serum-free culture. FSH and IGF1 both stimulated estradiol secretion and inhibited MMP2 and MMP9 mRNA abundance. In contrast, EGF and FGF2 both inhibited estradiol secretion but had no effect on MMP expression. At physiological doses, none of these hormones altered the proportion of dead cells. Although we cannot link MMP expression with apoptosis, the specific down regulation by the gonadotropic hormones FSH and IGF1 in vitro suggests that excess MMP2 and MMP9 expression is neither required nor desired for follicle development.
Highlights
Bovine antral follicles are composed of several cell types including granulosa and theca cells, fibroblasts and endothelial cells
The objective of the present study was to determine the effects of FSH and growth factors on granulosa cell matrix metalloproteinases (MMP) expression in bovine granulosa cells, and to determine if changes in Extracellular matrix (ECM) remodeling activity are associated with cell survival
Real-time PCR revealed the presence of MMP2 and MMP9 mRNA in granulosa cells
Summary
Bovine antral follicles are composed of several cell types including granulosa and theca cells, fibroblasts and endothelial cells. Plasmin is synthesized from plasminogen through plasminogen activators, and is an active protease that promotes degradation of components of the ECM in normal and malignant tissue as well as activation of matrix metalloproteinases (MMP) (Castellino and Ploplis, 2005; Rundhaug, 2005). The enzymes that degrade the protein material present in the ECM during its remodeling include the MMP and tissue plasminogen activator families. MMP gelatinase activity has been detected in cultured bovine theca and granulosa cells (Smith et al, 2005), the factors that control the expression of these proteins are unknown. The objective of the present study was to determine the effects of FSH and growth factors on granulosa cell MMP expression in bovine granulosa cells, and to determine if changes in ECM remodeling activity are associated with cell survival
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