Endocrinology, Vol 137, 438-446, Copyright © 1996 by Endocrine Society

ARTICLES

Insulin-like growth factor binding protein-3 inhibits gonadotropin- induced ovulation, oocyte maturation, and steroidogenesis in rabbit ovary

Y Yoshimura, S Nagamatsu, M Ando, M Iwashita, T Oda, Y Katsumata, S Shiokawa and Y Nakamura
Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan.

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.

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