INVOLVEMENT OF ANGIOTENSIN-II IN THE PROCESS OF GONADOTROPIN-INDUCED OVULATION IN RABBITS

In the present study we investigated the role of angiotensin II (Ang I I) receptor subtypes in gonadotropin-induced ovulation, oocyte maturat ion, and ovarian steroidogenesis and prostaglandin (PG) production in in vitro-perfused rabbit ovaries. The addition to the perfusate of PD1 23319, a nonpeptide Ang II antagonist with a high affinity for AT(2) r eceptors, inhibited hCG-induced ovulation in a dose-dependent manner, whereas CV-11974, a nonpeptide AT(1) receptor antagonist, had no effec t. The majority of ovulated ova and follicular oocytes resumed meiotic maturation in response to hCG; and PD123319, but not CV-11974, signif icantly inhibited hCG-induced oocyte maturation. The addition of both Ang II receptor antagonists to the perfusate had no significant effect on the concentration of progesterone in the perfusate of hCG-treated ovaries, whereas PD123319 inhibited the hCG-stimulated production of e stradiol. The production of PCE(2) and PGF(2 alpha) was significantly increased at 6 h in hCG-treated ovaries compared with ovaries before h CG administration. PD123319 inhibited the hCG-stimulated production of PGs by perfused rabbit ovaries in a dose-dependent manner, indicating that hCG-induced PG synthesis is mediated, at least in part, via the activation of AT(2) receptors. Ovulatory efficiency in ovaries perfuse d with or without PD123319 in the presence of hCG was significantly co rrelated with PG production by perfused rabbit ovaries 12 h after expo sure to hCG (r = 0.6553 for PGE(2), p < 0.001; r = 0.4758 for PGF(2 al pha), p < 0.05). In conclusion, Ang II exerts complex and coordinated control on at least two distinct aspects in the normal ovulatory proce ss, ovulation and oocyte maturation. Ang II produced locally by gonado tropin exposure may be a part of a novel intraovarian paracrine or aut ocrine control mechanism that operates via the AT(2) receptor in the o vary.