| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1999: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Research Abstract |
Although the vast majority of ovarian follicles undergo a degenerative process termed atresia, the fundamental mechanism of this atretic process is largely unknown. Survival and apoptosis of ovarian granulosa cells (GCs) play a crucial role in determining the number of follicles destined to ovulate. Follicle-stimulating hormone (FSH) is thought to be a critical factor for the survival of GCs and follicular growth. Our laboratory recently found that FSH-induced activation of extracellular-regulated kinase (ERK), which is first identified MAP kinase, is changed in a cAMP-dependent to a cAMP-independent pathway during follicular development. The aim of this study is to examine the pathway of FSH-induced ERK activation in more detail, involving the meaning of the change in the dependency on cAMP.
We have obtained the following results.
1. Lysophosphatidic acid, a component of the serum, induced the change in the dependency on cAMP.
2. Activation of phospholipase C was essential for FSH-elicited ERK activation in both differentiated and undifferentiated GCs prepared from mature and immature follicles, respectively, which is inconsistent with previous reports.
3. cAMP was not necessary for the survival of differentiated GCs, rather promoted apoptosis.
4. FSH-dependent survival of GCs requires the activities of ERK and p38, another type of MAP kinases. Interestingly, p38 activation is also implicated in apoptosis of GCs induced by oxidative stress.
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