Characterization of angiotensin II receptor type 2 during differentiation and apoptosis of rat ovarian cultured granulosa cells

We examined the change in the content of angiotensin II (AII) receptor type 2 (AT₂) during differentiation and apoptosis of rat ovarian granulosa cells in culture. The AT₂ content was not changed by follicle stimulating hormone (FSH), a differentiation factor of granulosa cells, but was markedly increased in FSH-free media. The cells cultured without FSH underwent internucleosomal DNA fragmentation characteristic of apoptosis, which occurs during follicle atresia. AII augmented the increase in the AT₂ content in the absence of FSH. This AII-induced augmentation was suppressed by the AT₂-selective antagonist PD123319 but not by Dup753, an antagonist specific for type 1 receptor, suggesting that AII up-regulates the AT₂ expression via AT₂ itself. These data strongly support the hypothesis that AT₂ might modulate the onset and progression of follicle atresia involving apoptosis of granulosa cells.