An aminopeptidase inhibitor, bestatin, enhances gonadotrophin-stimulated ovulation in mice.

The role of aminopeptidases in follicular growth and/or ovulation in vivo was examined. We injected an inhibitor of cell-surface aminopeptidases, bestatin (4 mg/ml, 100 microliters), i.p. four times during 2 days into 20 day old female ICR mice, in which follicular growth and ovulation were stimulated by pregnant mare's serum gonadotrophin (PMSG, 5 IU) and human chorionic gonadotrophin (HCG, 5 IU). The number of ovulated oocytes was estimated by counting the number of oocytes in the oviduct 19 h after HCG injection. The mean +/- SD number of ovulated oocytes in bestatin-treated mice was significantly higher than that in control mice [47.00 +/- 18.13 (n = 26) versus 35.90 +/- 10.14 (n = 28), P < 0.01]. To confirm the direct effect of bestatin on the ovary, bestatin (2 mg/ml, 3 microliters) or its stereoisomer (2 mg/ml, 3 microliters) with very weak inhibitory activity was unilaterally injected into the ovarian bursa 24 h before the administration of PMSG. As a control, buffer (3 microliters) was injected into the contralateral bursa. In some experiments, bestatin (2 mg/ml, 3 microliters) was injected just before HCG administration. The administration of bestatin via the ovarian bursa prior to PMSG administration significantly increased the number of ovulated oocytes per oviduct from the treated compared with the contralateral ovary [23.70 +/- 9.61 versus 17.10 +/- 5.83 (n = 25), P < 0.01], whereas its stereoisomer elicited no significant effects. The administration of bestatin just before HCG administration also had no effect. These findings indicate that membrane-bound peptidase(s) present on murine ovarian cells is an important regulating factor(s) of follicular growth and/or ovulation.