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In order to assess prostatic tissue as a target for receptor-mediated estrogen action, we have examined the regulation of estrogen (ER) and progestin receptors (PgR) by estrogen, antiestrogen, and progesterone in cytosolic and nuclear fractions of the R3327H (Dunning) prostatic adenocarcinoma of the rat. Twenty micrograms diethylstilbestrol (DES) with or without 800 micrograms tamoxifen (Tam) were injected s.c. in oil 5 times weekly for 2 weeks. Controls were given oil only. Estrogen receptor assays were carried out using [3H]estradiol and a hydroxylapatite exchange method. Progestin receptors were assayed using [3H]R5020 and dextran-coated charcoal to separate free and bound steroid. All binding data were evaluated by using Scatchard analysis. Treatment with DES depleted cytosolic ER, promoted association of ER with the nuclear fraction, and concomitantly increased PgR concentrations in amounts proportional to nuclear ER. Treatment with Tam alone resulted in higher nuclear ER concentrations than treatment with DES, but induced only one-fifth the amount of PgR. Treatment with DES plus Tam resulted in similar nuclear ER concentrations as with Tam alone, but PgR concentrations were intermediate between those observed with DES alone and Tam alone. Thus Tam exhibited both estrogenic and antiestrogenic properties. In this experiment, the same cytosolic and nuclear extracts were also assayed for ER by using monoclonal antibodies to the receptor in an enzyme immunoassay. No significant differences were observed between the results obtained by the radioligand and enzyme immunoassay methods in the cytosol and nuclear fractions from the control and DES-treated tumors. However in both Tam-treated groups, the ER values obtained by the enzyme immunoassay method were significantly higher than those obtained by the radioligand method in both cytosolic and nuclear fractions. This confirms the observations made by others in female target organs, that monoclonal antibody to ER reacts differently with the Tam-bound ER complex than with the estradiol-bound ER complex. In a separate experiment, administration of progesterone with DES decreased the concentration of nuclear ER to less than one-half that observed after administration of DES alone, with proportional decreases in both cytosolic and nuclear PgR. All these observations indicate that the control of ER and PgR concentrations in this prostatic tumor is identical to that observed in female rat target organs. Use of an immunohistochemical method for the detection of ER in frozen sections indicated that the receptor was localized in the glandular epithelium in both control and DES-treated tumors.
B G Mobbs, and
I E Johnson, and
E R DeSombre, and
J Toth, and
A Hughes
December 1979,
The Journal of clinical endocrinology and metabolism,
B G Mobbs, and
I E Johnson, and
E R DeSombre, and
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A Hughes
August 1977,
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B G Mobbs, and
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B G Mobbs, and
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July 1983,
Canadian journal of biochemistry and cell biology = Revue canadienne de biochimie et biologie cellulaire,
B G Mobbs, and
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June 1981,
Endocrinology,
B G Mobbs, and
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March 1977,
Annals of the New York Academy of Sciences,
B G Mobbs, and
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B G Mobbs, and
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E R DeSombre, and
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