Abstract.A number of endocrine and paracrine factors regulate the follicular growth and atresia, which are closely associated with granulosa cell survival and apoptosis. However, the molecular mechanisms underlying the intracellular events induced by these factors are poorly understood. Here, we describe the correlation of mitogen-activated protein kinase (MAPK) activities with granulosa cell survival and apoptosis, and the cellular functions of protein tyrosine phosphatases (PTPs) in these cells based on our recent data. MAPKs play key roles in various cellular responses because numerous extracellular stimuli are integrated into MAPKs. The protein phospho-Tyr level regulated by protein tyrosine kinases (PTKs) and PTPs is a major control mechanism for processes as diverse as cell survival, proliferation, differentiation, and metabolism. Although PTKs are critically involved in granulosa cell survival and proliferation, there are no reports indicating the roles of PTPs in the ovary except for ours. Information about MAPKs and PTPs in these cells will provide a basis for the understanding of the molecular mechanisms controlling the fate of follicles. Key words: Mitogen-activated protein kinase (MAPK), Protein tyrosine phosphatase (PTP), Granulosa cell, Apoptosis, Adenovirus (J. Reprod. Dev. 50: [47][48][49][50][51][52][53][54][55] 2004) ver 99% of ovarian follicles in mammals undergo a degenerative process called atresia, which is characterized by granulosa cell apoptosis [1,2]. In contrast, only a few follicles mature and reach ovulation under the cyclic gonadotropin stimulation. The selection of granulosa cell apoptosis or survival is a critical process in determining the fate of follicles. To date, a number of endocrine and paracrine factors have been shown as survival or apoptosis-inducing factors for these cells in vivo and in vitro [1,2], but the molecular mechanisms underlying the induced intracellular events are poorly understood. In this review, we describe the correlation of mitogenactivated protein kinase (MAPK) activities with granulosa cell survival and apoptosis, and the cellular functions of protein tyrosine phosphatases (PTPs) in granulosa cells based on our recent data [3][4][5]. Both MAPKs and PTPs are considered important regulators for granulosa cell survival, proliferation, differentiation and apoptosis as they are in other types of cells. Correlation of MAPK Activities with Granulosa Cell Survival and Apoptosis MAPK familyA vast number of extracellular stimuli are integrated into MAPKs that conversely affect many of the signaling pathways induced by these stimuli.
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