ANGIOTENSIN-II INDUCES OVULATION AND OOCYTE MATURATION IN RABBIT OVARIES VIA THE AT(2) RECEPTOR SUBTYPE

The present study was undertaken to investigate the role of angiotensi n II (Ang II) in ovulation and ovarian steroidogenesis and prostagland in (PG) production via the Ang II receptors in rabbit ovaries. In in v itro perfused rabbit ovaries, PD123319, a selective nonpeptide antagon ist for AT(2) receptors, reduced the Ang II-induced ovulation in a dos e-dependent manner, whereas CV-11974, a selective nonpeptide antagonis t for AT(1) receptor, did not affect the Ang II-induced ovulation. Ang II also significantly stimulated the meiotic maturation of ovulated o va and follicular oocytes in the absence of gonadotropin. The addition of PD123319 at 10(-6) M to the perfusate significantly inhibited the Ang II-induced oocyte maturation. Ang II did not stimulate the product ion of progesterone by perfused rabbit ovaries but Significantly stimu lated the production of estradiol (E(2)) and PGs. When PD123319 at 10( -6) M was added to the perfusate 30 min before the onset of Ang II adm inistration, the Ang II-stimulated production of E(2) and PGs was sign ificantly blocked. Saralasin, a peptide analog of Ang II, inhibited th e specific binding of [I-125]iodo-[Sar(1),Ile(8)] Ang II to rabbit ova rian membranes in a concentration-dependent manner, yielding an inhibi tory constant (IC50) value of 1.58 x 10(-9) M. PD123319 and CV-11974 a lso inhibited the binding of [I-125]iodo-[Sar(1),Ile(8)] Ang II; howev er, PD123319 and CV-11974 were 15 and 40 times less potent than sarala sin, respectively. Autoradiographic study revealed that an intense loc alization of Ang II receptors in the rabbit ovaries was present in the granulosa cell layers and the stroma of the preovulatory follicles. A T(2) receptors were predominantly located in granulosa cells, whereas AT(1) receptors were more concentrated in the stroma and thecal cell l ayers. In summary, Ang II induced ovulation and oocyte maturation and stimulated the production of E(2) and PG by perfused rabbit ovary in v itro via the AT(2) receptor. Thus, locally produced Ang II may be part of a novel intraovarian paracrine or autocrine control mechanism duri ng the ovulatory process.