RECOMBINANT FSH (ORG32489) INDUCES FOLLICLE GROWTH AND OVULATION IN THE ADULT CYCLIC RAT

The effects of a single injection of recombinant human FSH (rhFSH; Org 32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioest rus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ov ulation rate on the day of expected oestrus. However, an additional, p recocious ovulation resulting in a normal number of corpora lutea (13. 3 +/- 0.4, n=6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vagi nal plugs the next morning, was observed at this ovulation. Follicle c ounts showed a loss of large antral follicles due to ovulation and inc reased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as we ll as additional recruitment of new antral follicles. The endogenous s erum FSH concentration on the subsequent day of oestrus (65 h after rh FSH injection) as well as recruitment of small antral follicles were l ower in the rhFSH-treated rats than in saline-treated controls. The ov ulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group. Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH p reparation (i.e. metrodin). Furthermore, the direct induction of ovula tion by rhFSH or metrodin could not be prevented by the injection of a n LHRH antagonist. It was concluded that rhFSH can induce acute ovulat ion in rats, and stimulates follicular development directly or indirec tly through increased FSH levels after ovulation. It induces antral fo llicle growth and decreases early atresia in small antral follicles.