FOLLICULOGENESIS IN HYPOPHYSECTOMIZED RATS AFTER TREATMENT WITH RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE

To examine the role of FSH and LH in follicular growth and atresia, im mature hypophysectomized (hyper) rats were treated twice daily for fou r days with a total dose either of 2.5 to 40 IU recombinant human FSH (recFSH; Org 32489) or of 8 IU recFSH supplemented with 0.2 to 5 IU hC G. RecFSH alone caused dose-dependent increases in ovarian weight and intraovarian estradiol (E(2)) but was unable to elevate circulating E( 2) levels. The number of antral follicles was also increased in a recF SH dose-dependent manner, and a gradual shift of small antral follicle s to large preovulatory follicles was noted. The tatter ovulated after a single bolus injection of 10 IU hCG. In comparison with follicles f rom hyper vehicle-treated animals, these follicles showed a diminished incidence of atresia, especially in the smallest size class of antral follicles. A total dose of greater than or equal to 10 IU recFSH incr eased uterine weight accompanied by endometrium proliferation. When 8 IU recFSH was supplemented with 0.2 to 5 IU hCG, ovarian weight was au gmented in an hCG dose-dependent fashion, but no further increases in total number of antral follicles were noted except with the highest hC G dose given. Nevertheless, addition of relatively low doses of hCG ca used considerable shifts of small follicles to large, preovulatory fol licles. Furthermore, supplementation with hCG, especially low dosages of hCG (0.2 and 0.5 IU), reduced the incidence of atresia in antral fo llicles of all size classes. These data suggest that in the complete a bsence of LH activity, recFSH induces follicular growth up to the stag e of mature preovulatory follicles and induces ovarian estradiol produ ction and endometrium proliferation. The addition of small amounts of LH activity increases the percentage of healthy follicles.