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Administration of 4 mg of the antiprogestagen RU486 to 4-day cyclic rats during proestrus induced a 1-day shortening of the ovarian cycle, a reduction in ovulatory rate that was reversed by an injection of exogenous human (h)FSH in the evening of proestrus, and the absence of the LH-inhibiting effect of exogenous estradiol resulting in a 24-h advancement of the preovulatory LH surge. These effects were not present when RU486 was injected during estrus. RU486 injected during either proestrus or estrus increased serum levels of LH and estradiol-17 beta in diestrus and reduced the magnitude of the preovulatory surge of gonadotropins. Only rats treated with RU486 during estrus showed increased follicular size and acceleration of oocyte maturation on proestrous afternoon. These results demonstrate that in 4-day cyclic rats receiving an injection of RU486 during proestrus, the low ovulatory rate is a consequence of a reduced secondary FSH surge-induced follicular recruitment in the afternoon of estrus and that the shortening of the estrous cycle is the result of an advanced desensitization to the negative feedback of estradiol on LH secretion. Furthermore, since the administration of RU486 during proestrus blocks both follicular and luteal progesterone actions whereas injection during estrus blocks only luteal progesterone actions, we suggest that, in 4-day cyclic rats, the actions of progesterone during diestrus retard maturation of follicles via the lowering of serum LH concentrations and that the actions of progesterone in proestrous evening delay the desensitization to the negative estrogen feedback on LH secretion.

Follicular and Luteal Progesterone Play Different Roles Synchronizing Pituitary and Ovarian Events in the 4-Day Cyclic Rat1