Localization of angiotensin II receptors in ovarian follicles and the identification of angiotensin II in rat ovaries

Specific, high-affinity (K(d) ~ 0.6 nM), and saturable (3.3 fmol/mg of tissue, wet weight) binding of 125I-labeled [Sar1,Ile8[angiotensin II to rat ovarian membranes was observed. Displacement of 125I-labeled [Sar1,Ile8]angiotensin II binding to rat ovarian membranes by angiotensin II analogs and fragments resembled the potency order of these compounds on angiotensin II receptors in other tissues: [Sar1,Ile8]angiotensin II > angiotensin II > des-Asp-angiotensin II > angiotensin I > des-Asp1,Arg2-angiotensin II. Several unrelated peptides, including follicle-stimulating hormone at 10 μM, did not displace ovarian 125I-labeled [Sar1,Ile8]angiotensin II binding. Autoradiograms of 125I-labeled [Sar1,Ile8]angiotensin II binding to ovarian sections indicated that the angiotensin II receptor binding sites were localized exclusively to a subpopulation of follicles, occurring on the granulosa and theca interna cells. Other follicles were devoid of 125I-labeled [Sar1,Ile8]angiotensin II binding sites. Angiotensin II immunoreactive material was also identified in the ovary. The concentration of ovarian Ang II immunoreactivity was 8- to 75-fold greater than that of plasma, was not reduced in bilaterally nephrectomized rats, and was shown by high-pressure liquid chromatographic analysis to be the native angiotensin II octapeptide. The presence of angiotensin II and its receptor binding sites in the ovary suggests a role for angiotensin II as a regulator of ovarian function.