Interaction of putative estrogens and the estrogen receptor system in Leydig cells in the BALB/c mouse testis resulting in the initiation of DNA synthesis

Continuous administration of estrogens for 7-9 months, both steroidal and nonsteroidal, to male BALB/c mice, leads to the formation of testicular Leydig cell tumors. Three days following the subcutaneous implantation of a pellet of estrogen in cholesterol, there is a peak in the incorporation of 3H-thymidine into the DNA of the interstitial cells. These effects are hypothesized to be mediated by the estrogen receptor system in the Leydig cell. Common experimental techniques for the measurement of hormone binding, such as dextran coated charcoal treatment, proved to be impossible to employ in this system, therefore a procedure was developed using hydroxyapatite to obtain binding data. The cytosolic estrogen receptor was found to have a dissociation constant for estradiol-17β of 6.5 x 10-8 M, while that of the nuclear estrogen receptor was 1.25 x 10-8 M. Competition assays were utilized to determine the cytosolic estrogen receptor's affinity for nonsteroidal estrogens, steroidal estrogens, and triphenylethylene