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Studies on the Progesterone Receptor Content and Steroid Metabolism in Normal and Pathological Human Breast Tissues^*

RICARDO V. LLOYD

Department of Pathology, University of Wisconsin Hospitals, Madison, Wisconsin 53706

Breast tissues from 44 patients who had normal tissues (9) or pathologic tissues designated as fibrocystic disease (8), fibroadenoma (1), and carcinoma (26) were examined for receptor content and metabolism of progesterone. The last 7-consecutive cases of carcinoma were also examined for testosterone metabolism. When the dextran-coated charcoal assay technique was used to analyze the progesterone receptor content of the cytosols, 3 of 9 normal breast tissues (33%), 1 of 8 tissues with fibrocystic disease (12%), and 10 of 26 breast carcinomas (38%) had progesterone receptor levels greater than 10 fmol/mg protein. In the presence of 30% glycerol and 1 µM cortisol, the dissociation constant for the [³H]progesterone-receptor complex was 1.9 ± 1.1 (SE) nM. Although 4 of 5 cases analyzed by sucrose density gradient sedimentation showed only a 4S peak for the progesterone receptor complex, 1 of 5 cases studied with [³H]progesterone and the 2 cases studied with [³H]R5020 (³Hlabeled 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) had radioactive peaks in the 7-8S and the 4S regions of the sucrose gradients.

After incubation of minced tissues with [³H]progesterone, 5 pregnane-3,20-dione, 3-hydroxy-5-pregnan-20-one, 20-hydroxy-pregn-4-en-3-one, 20-hydroxy-5-pregnan-3-one, and 5 pregnane-3-20-diol were found, indicating the presence of 5 reductase, 20-hydroxysteroid dehydrogenase, and 3-hydroxysteroid dehydrogenase activities. Normal breast tissues had the lowest levels of all three enzyme activities, while tissues with fibrocystic disease had the highest 5-reductase activity. Carcinoma tissues had intermediate levels of 5-reductase and the highest levels of the other two enzyme activities. There was increased production of 5-reduced metabolites with increasing epithelial cellularity.

After incubation of breast carcinoma tissues with [³H]testosterone, 5-androstane-3, 17β-diol, 17β-hydroxy-5-androstan-3-one, and androstenedione were found. The presence of NADPH in the incubation medium increased the amounts of 5 reduced products formed.

5-Dihydroprogesterone, the principal metabolite of progesterone in these studies, competed for the progesterone receptor in 2-h competition studies using the dextran-coated charcoal method, but with lower affinity than R5020 or progesterone.

These results indicate that detectable levels of progesterone receptors are present in normal as well as pathologic breast tissues and that 5a-reductase and other enzyme activities are present in variable amounts in different types of breast tissues. (J Clin Endocrinol Metab 48: 585, 1979)

^* This work was supported by PHS Grant 5T32-GM-07194-03 and Institutional Research Grant IN-35-Q.

Recipient of a fellowship from the American Cancer Society.

Received September 7, 1978.

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