title: Insulin-like growth factor binding protein-3 inhibits gonadotropin-induced ovulation, oocyte maturation, and steroidogenesis in rabbit ovary.
abstract: The effects of insulin-like growth factor binding proteins (IGFBPs) on human CG (hCG)-induced oocyte maturation, ovulation, steroidogenesis, and intrafollicular plasminogen activator (PA) activity were investigated in rabbit ovaries perfused in vitro. The addition of IGFBP-3, but not IGFBP-1, to the perfusate dose dependently inhibited hCG-induced ovulation, whereas ovulation failed to occur in any ovaries perfused with medium or IGFBP-3 alone. IGFBP-3 (100 ng/ml) significantly inhibited the resumption of meiosis in ovulated ova and follicular oocytes in hCG-treated ovaries, as well as the hCG-stimulated production of estradiol (E2), but not progesterone, by the perfused ovaries. Intrafollicular PA activity increased significantly within 1 h after exposure to hCG, reaching a maximum at 4 h; IGFBP-3 significantly inhibited hCG-stimulated intrafollicular PA activity. The blockade of hCG-induced ovulation by IGFBP-3 correlated with the reduction in intrafollicular PA activity. Treatment with hCG induced a 2.5-fold increase in intrafollicular IGF-I messenger RNA levels at 4 h. Although ovulation failed to occur in ovaries treated with IGF-I (100 ng/ml) in the absence of gonadotropin, IGF-I significantly increased the mean diameter of preovulatory follicles and stimulated the resumption of meiosis in follicular oocytes. These effects of IGF-I on follicular growth and oocyte maturation were significantly inhibited by IGFBP-3 (100 ng/ml). Furthermore, IGFBP-3 significantly inhibited the IGF-I-stimulated production of E2. In conclusion, IGFBP-3, but not IGFBP-1, blocked the stimulatory effects of hCG in the ovulatory process. These findings suggest that IGFBP-3 may contribute to the regulation of intrafollicular PA activity during follicular development and ovulation evoked by gonadotropin exposure, at least in part, via neutralizing endogenously produced IGF-I.
authors.affiliation: Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: S
authors.initials: S
authors.lastname: Nagamatsu
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: M
authors.initials: M
authors.lastname: Iwashita
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: Y
authors.initials: Y
authors.lastname: Katsumata
authors.forename: S
authors.initials: S
authors.lastname: Shiokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010060:Ovulation; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
chemical_list: D006063:Chorionic Gonadotropin; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D004958:Estradiol; D007334:Insulin-Like Growth Factor I