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Resistance of the Ovary to Blockade of Aromatization with Aminoglutethimide^*

Department of Medicine, Division of Endocrinology, Specialized Cancer Center of The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania 17033; the Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710

Address requests for reprints to: Dr. Richard J. Santen, Division of Endocrinology, Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033.

Aminoglutethimide (AG) is a potent inhibitor of aromatization in placental microsomes and in peripheral tissues in postmenopausal women. Aromatase inhibitors have been used to block estrogen production and induce breast tumor regression in rodents. To inhibit ovarian estrogen production, we administered various doses of AG and its highly potent D-stereoisomer to premenopausal women with breast carcinoma. However, at no dose level did AG consistently lower estrone and estradiol concentrations in plasma below those observed in normal menstruating women. Uniform increments in LH and FSH were also not observed. Only during the luteal phase were the levels of estradiol (but not estrone) significantly suppressed. These observations are best explained by the possibility that aromatase enzymes in the ovary, as opposed to those in the placenta and in peripheral tissues, are partially resistant to the effects of AG.

^* This work was supported in part by Contract NCI-53851 and Specialized Cancer Center Grant 1–P30-CA-18450 from the NCI and Grant RR-30 from the Division of Research Resources, NIH, Bethesda, MD.

Received December 24, 1979.

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