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Progesterone and Progesterone Receptors in Experimental Breast Cancer¹

Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78284

The synthetic progestin, R5020, has been used to demonstrate a progesterone receptor (PGR) in 7,12-dimethylbenz()anthracene-induced rat mammary tumors which binds hormone with high affinity (K_d 1 nM) and migrates at 7S and 4S on sucrose density gradients. Rats bearing growing tumors were ovariectomized-adrenalectomized at proestrus, tumors were biopsied 24 hr later, and estrogen receptor and PGR were determined by a single, saturating-dose dextran-coated charcoal assay. PGR values averaged 247 ± 27 fmoles/mg cytosol protein. When rats received injections of progesterone plus estradiol, biopsied tumors resumed growth and PGR levels were maintained. PGR was also unchanged in tumors growing on estradiol alone. Tumors regressed after withdrawal of progesterone + estradiol or of estradiol alone, and PGR uniformly fell to basal levels (<50 fmoles/mg cytosol protein). Estrogen treatment of regressed tumors restored both tumor growth and PGR.

In sum, castration with adrenalectomy induced rapid tumor regression and loss of PGR. Estradiol administration prevented tumor regression and PGR loss or restored PGR in regressed tumors. Progesterone alone failed to sustain tumor growth despite the initial presence of PGR.

¹ Supported in part by National Cancer Institute Grants CA 11378 and CB 23862, the American Cancer Society, and the Robert A. Welch Foundation.

² To whom requests for reprints should be addressed.

Received 9/27/76. Accepted 3/15/77.

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