The localization of androgens in two lines of transplantable mouse mammary tumors, one androgen dependent and the other autonomous, has been studied after the i.v. administration of 200 µCi (1.4 µg) of Δ4-androsten-17β-ol-3-one-1,2-3H to tumor-bearing mice. Whereas at 30 min the uptake of radioactivity was approximately equal in intact, dependent, and autonomous tumors, the level of radioactivity was almost 4 times higher in nuclei of dependent cells than in nuclei of autonomous cells. Metabolites of δ4-androsten-17β-ol-3-one-1,2-3H were identified by thin-layer and gas-liquid chromatography, and no appreciable differences were found in the intracellular concentrations of δ4-androsten-17β-ol-3-one and 5α-androstan-17β-ol-3-one. Steroid-binding protein was precipitated from the 105,000 × g supernatant fraction of cytoplasm (cytosol) with ammonium sulfate, and binding was measured by gel filtration. The amount of steroid bound to the receptors was 4 times higher in cytosol of dependent cells than in cytosol of autonomous cells, and there was a corresponding difference in the specific activities of the binding proteins. These results are consistent with the view that the impaired incorporation of androgens into nuclei of autonomous cells is related to a reduced concentration of cytoplasmic receptors.
This project was financed by grants from the Medical Research Council of Canada (MA 3729), the National Cancer Institute of Canada, and the Ontario Cancer Treatment and Research Foundation.