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The majority of ovarian follicles undergo atresia through a mechanism involving apoptotic cell death. Although GnRH and its agonists have been shown to suppress ovarian growth and differentiation in hypophysectomized rats, studies on the induction of follicle atresia by GnRH are contradictory. In the present study, the direct effect of GnRH on the occurrence of apoptosis in the ovary was investigated in hypophysectomized estrogen-treated immature rats. Starting 2 days after operation and estrogen capsule implantation, rats were treated with a GnRH agonist (GnRHa; [desGly10,D-Phe6,Pro9-N-ethylamide] GnRH; 50 micrograms/injection, twice daily). Total ovarian DNA was isolated 48 h later, labeled at the 3'ends with [32P]dideoxy ATP, and size-fractionated. Compared to that in control animals, treatment with GnRHa increased DNA fragmentation in multiples of 180 basepairs, a hallmark of apoptosis …