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, immature hypophysectomized (hypox) rats were treated twice daily for four 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 hCG. RecFSH alone caused dose-dependent increases in ovarian weight and intraovarian estradiol (E2) but was unable to elevate circulating E2 levels. The number of antral follicles was also increased in a recFSH dose-dependent manner, and a gradual shift of small antral follicles to large preovulatory follicles was noted. The latter ovulated after a single bolus injection of 10 IU hCG. In comparison with follicles from hypox vehicle-treated animals, these follicles showed a diminished incidence of atresia, especially in the smallest size class of antral follicles. A total dose of > or = 10 IU recFSH increased uterine weight accompanied by endometrium proliferation. When 8 IU recFSH was supplemented with 0.2 to 5 IU hCG, ovarian weight was augmented in an hCG dose-dependent fashion, but no further increases in total number of antral follicles were noted except with the highest hCG dose given. Nevertheless, addition of relatively low doses of hCG caused considerable shifts of small follicles to large, preovulatory follicles. Furthermore, supplementation with hCG, especially low dosages of hCG (0.2 and 0.5 IU), reduced the incidence of atresia in antral follicles of all size classes. These data suggest that in the complete absence of LH activity, recFSH induces follicular growth up to the stage of mature preovulatory follicles and induces ovarian estradiol production and endometrium proliferation. The addition of small amounts of LH activity increases the percentage of healthy follicles.
Mannaerts
B
B
Medical R&D Unit, Organon International bv, Oss, The Netherlands.
Uilenbroek
J
J
Schot
P
P
De Leeuw
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005496:Follicular Atresia / Q000187:drug effects; D006801:Humans; D007016:Hypophysectomy; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000033:anatomy & histology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014599:Uterus / Q000033:anatomy & histology
D006063:Chorionic Gonadotropin; D011994:Recombinant Proteins; D004958:Estradiol; D005640:Follicle Stimulating Hormone