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Regulation of nuclear factor-kappaB (NF-kappaB) activity and apoptosis by estradiol in bovine granulosa cells.

Although atresia of bovine follicles is associated with apoptosis of granulosa cells, the signals initiating this cell death have not been resolved. NF-kappaB has been implicated as an important regulator of genes controlling apoptosis, and previous studies indicate that estradiol may modulate NF-kappaB activation. We hypothesized that estradiol activates NF-kappaB, and thus, inhibits apoptosis in granulosa cells of dominant follicles. Dominant follicles were collected on Days 4, 6, and 8 of the first follicular wave following ovulation and assayed for NF-kappaB activity. Concentrations of estradiol in follicular fluid decreased on Day 6 compared to Day 4 of the wave. NF-kappaB activity in granulosa cells was lower on Day 8 compared to Days 4 and 6. In vitro, NF-kappaB activity and minimal incidence of apoptosis (<4%), as measured by Annexin V and TUNEL assays, were associated with production of estradiol. However, inhibition of NF-kappaB in vitro led to a suppression of apoptosis. These results indicate that follicular NF-kappaB activation is associated with estradiol production. However, whether NF-kappaB is playing a pro- or anti-apoptotic role in granulosa cells of the dominant bovine follicle remains to be elucidated.