THE STEROID ANTAGONIST RU486 GIVEN AT PRO-ESTRUS INDUCES HYPERSECRETION OF FOLLICLE-STIMULATING-HORMONE FROM ESTRUS AFTERNOON TO EARLY METESTRUS IN THE RAT

Administration of the steroid antagonist RU486 to cyclic rats at pro-o estrus blunts the preovulatory surge of LH and suppresses the first an d second surges of FSH, In addition, administration of oestradiol to R U486-treated rats reactivates the LH surge the following day. The pres ent study explored the effects of RU486 (4 mg/0.2 ml oil), administere d at 0800 h on the day of pro-oestrus, on serum FSH and LH concentrati ons through oestrus and early metoestrus. RU486 induced a hypersecreti on of FSH, which started at 1400 h on the day of oestrus and was maint ained until 0800 h on the day of metoestrus. Because the timing and ma gnitude of this secretion of FSH were similar to those of the periovul atory secretion of FSH during pro-oestrus and early oestrus in intact cyclic rats, we investigated the effects of: 1) LHRH antagonist (LHRHa ) injected at either 0900 h or 2000 h on the day of oestrus, 2) oestra diol benzoate injected at 1600 h on the day of prooestrus and at 0900 h on the day of oestrus, 3) bovine follicular fluid (bFF) given either at 1100 h or at 2000 h on the day of oestrus, or 4) adrenalectomy (AD X) at 1100 h on the day of oestrus, on serum FSH and LH concentrations at 1800 h on the day of oestrus and at 0200 h on the day of metoestru s in rats injected with RU486 at pro-oestrus. The results showed that 1) both components (late oestrus and early metoestrus) of FSH hypersec retion in RU486-injected rats in pro-oestrus were inhibited by oestrad iol benzoate and bFF, 2) the metoestrous component was not affected by LHRHa, whereas the oestrous component was partially reduced, and 3) A DX partially reduced serum FSH concentrations only on the day of metoe strus, possibly because, as the serum concentrations of corticosterone reflected, the antiglucocorticoid activity of 4 mg RU486 lasted only 24 h, The results support the hypothesis that blockade of progesterone actions at pro-oestrus results in the maintenance of the daily neural signal that activates the release of gonadotrophins. Whereas the expr ession of LH secretion requires high levels of oestradiol, FSH secreti on is expressed against a background of low oestradiol levels. The res ults of this study also indicate that the release of FSH during oestru s and metoestrus in rats injected with RU486 at pro-oestrus is a conse quence of the lack of ovarian negative feedback inhibition on the pitu itary.