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Characterization of Angiotensin I-Converting Enzyme (ACE)-Containing Follicles in the Rat Ovary during the Estrous Cycle and Effects of ACE Inhibitor on Ovulation^*

ADIL I. DAUD, F. MERLIN BUMPUS and AHSAN HUSAIN

Department of Heart and Hypertension Research, Research Institute of the Cleveland Clinic Foundation Cleveland, Ohio 44195-5071

Address all correspondence and requests for reprints to: Ahsan Husain, Ph.D., Department of Heart and Hypertension Research, Research Institute of the Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195-5071.

Abstract

Ovarian angiotensin I (Ang I)-converting enzyme (ACE), estimated by the specific binding of the ACE inhibitor [¹²⁵I]iodo-MK-351A, is localized on multiple ovarian structures, including follicular granulosa cells, corpora lutea, germinal epithelium, and ovarian blood vessels, but total ovarian ACE does not display a cyclic pattern of variation during the rat estrous cycle. We have previously shown that ACE is localized on the granulosa cell layer of a subpopulation of rat ovarian follicles. Our present study shows that ovarian granulosa cells contain high affinity [binding site affinity (K_d), -90 pM] and low capacity [binding site density (BmM), -12 fmol/2.5 x 105 cells] [¹²⁸I]iodo-MK-351A-binding sites and convert [¹²⁵I]iodo- Ang I to [¹²⁵I]iodo-Ang II (>85% of this conversion was inhibited by the ACE inhibitor captopril). Throughout the rat estrous cycle, 94-100% of developing follicles and 89-96% of atretic follicles contained high levels of ACE; however, ACE was either not observed or its levels were very low in preovulatory follicles. These findings indicate the presence of high levels of biologically active ACE on the surface of granulosa cells and suggest a potential role for follicular ACE in early stages of follicular maturation and atresia.

Although ACE is known to process a variety of peptides found within the ovary, and these peptides may have opposing effects on follicular maturation, we attempted to define the cumulative effect of ACE inhibition on follicular maturation. Short and long term (6- and 14-day) infusions of captopril (6-day, 30.5 ± 3.5 ova; 14-day, 28.5 ± 7.5 ova) in immature rats, in which ovulation was induced by sequential treatments with PMSG and hCG, did not significantly affect ovulation compared with that in vehicle-infused control rats (6-day, 22.4 ± 2.4 ova; 14-day, 20.8 ± 3.1 ova), suggesting that ACE inhibition does not modify the follicular selection process in a way that affects ovulation. This may explain the lack of any reports of adverse effects of clinically used ACE inhibitors on ovulation. (Endocrinology 126: 2927–2935, 1990)

Footnotes

^* This work was supported by a grant from the Reinberger Foundation and NIH Grant HD-23925.

Recipient of a fellowship from the American Heart Association, Northeast Ohio Affiliate.

Received January 16, 1990.

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