Crosstalk Among Multiple Signaling Pathways Controlling Ovarian Cell Death.
Ovarian cell death is an essential process for the homeostasis of ovarian function in human and other mammalian species. It ensures the selection of the dominant follicle and the demise of excess follicles. In turn, this process minimizes the possibility of multiple embryo development during pregnancy and assures the development of few but healthy embryos. Degeneration of the old corpora lutea in each estrous/menstrual cycle by programmed cell death is essential to maintain the normal cyclicity of ovarian steroidogenesis. Although there are multiple pathways that can determine cell death or survival, crosstalk among endocrine, paracrine and autocrine factors, as well as among protooncogenes, tumor suppressor genes, survival genes and death genes, plays an important role in determining the fate of ovarian somatic and germ cells. The establishment of immortalized rat and human steroidogenic granulosa cell lines and the investigation of pure populations of primary granulosa cells allows systematic studies of the mechanisms that control steroidogenesis and apoptosis of granulosa cells. These cells are the most abundant type of somatic follicular cell. Moreover, crosstalk between p53 and extracellular matrix components such as laminin, fibronectin and basic fibroblast growth factor, between cAMP- and p53-generated signals and between steroid hormones and Bcl-2, can explain some of the fine tuning that controls ovarian steroidogenesis and apoptosis. Further study of the mechanisms of ovarian cell death will lead to a better understanding of the processes involved and permit the formulation of novel strategies for the treatment of ovarian malfunctions, such as polycystic ovarian syndrome and ovarian cancer.
Amsterdam
A
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Gold
RS
Hosokawa
K
Yoshida
Y
Sasson
R
Jung
Y
Kotsuji
F