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Estrogen-Induced Progesterone Receptor in the Syrian Hamster Kidney. I. Modulation by Antiestrogens and Aindrogens^*

Research and Endocrine Services, Veterans Administration Hospital, 55417; and Departments of Pharmacology and Medicine, University of Minnesota Medical School Minneapolis, Minnesota, 55455

Address requests for reprints to: Dr. Jonathan J. Li, Veterans Administration Hospital, 54th Street and 48th Avenue South, Minneapolis, Minnesota 55417.

Abstract

Our previous studies demonstrated a specific progesterone receptor in the estrogen-induced and -dependent hamster renal carcinoma and provided evidence that estrogen treatment induces a 4S progesterone- binding component in renal cytosol of the hamster. This latter finding represented the first physiological change thus far reported during the induction period of estrogen renal tumorigenesis. The present studies indicated that the earliest appreciable increase in specific progesterone binding in kidneys of estrogen-primed hamsters occurred after 3 weeks of hormone treatment. The hormone specificity of the progesterone receptor in renal cytosol of estrogenized hamsters was ascertained by competitive binding assay and sucrose gradient centrifugation. These data indicate that the progesterone receptor is specific, since estrogens, androgens, and most progesterone metabolites did not compete appreciably for this receptor at 100-fold excess, whereas unlabeled progesterone markedly inhibited the binding at corresponding concentrations. Binding equilibrium measurements (K_a = 1.25–1.36 x 10⁹ M^-1) for the estrogeninduced progesterone receptor in the hamster kidney were similar to those obtained for the hamster uterus and renal carcinoma. Prolonged estrogen treatment did not influence the apparent minimal quantities of specific progesterone binding in hamster liver, lung, heart, or serum as well as in rat kidney. The amount of specific progesterone binding induced by estrogen in the hamster kidney (40–50 fmol/ml protein) was approximately 30 times greater than untreated levels. On the other hand, the concentration of progesterone receptor in the renal carcinoma (1,050 fmol/mg protein) is at least 520- fold higher than unprimed levels and approximately 17–20 times greater than estrogen-primed levels. Data presented herein also show that antiestrogens, such as nafoxidine and enclomiphene, but not MER-25 block the induction of specific progesterone binding by estrogen in the hamster kidney. Furthermore, androgen treatment is as effective as antiestrogens in inhibiting the increase in progesterone binding by estrogen. Similarly, hamsters previously treated with estrogen alone for 3-4 months and then subsequently treated with either nafoxidine, enclomiphene, or androgens with continued estrogen treatment resulted in the suppression of the estrogen-induced progesterone receptor response. These results are consistent with previous reports concerning the inability of estrogen to induce renal carcinoma in the hamster in the presence of antiestrogens or androgens.

Footnotes

^* This work was supported by Grant CA-22008 from the National Cancer Institute, NIH, DHEW and by the General Medical Research Fund, Research Service, V.A. Hospital. It was presented in part at the 59th Annual Meeting of The Endocrine Society, Chicago, IL, June 8–10, 1977.

Received February 6, 1978.

This article has been cited by other articles:

				J. J. Li, S. J. Weroha, M. F. Davis, O. Tawfik, X. Hou, and S. A. Li ER and PR in Renomedullary Interstitial Cells During Syrian Hamster Estrogen-Induced Tumorigenesis: Evidence for Receptor-Mediated Oncogenesis Endocrinology, September 1, 2001; 142(9): 4006 - 4014. [Abstract] [Full Text] [PDF]

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