Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone

This report describes the unexpected observation that testosterone-estradiol binding globulin (TeBG) binds 2-methoxyestradiol better than it binds either testosterone or 17 beta-estradiol. As determined by competitive displacement of 3H-testosterone from TeBG adsorbed onto a solid phase matrix of Con A-Sepharose, the relative binding activities of 2-methoxyestradiol, testosterone and 17 beta-estradiol for TeBG were 2.0, 1.0 and 0.32, respectively. In contrast, 2-methoxyestradiol, which is known to bind with low affinity to estrogen receptors, had only low affinity binding to the androgen receptor, as determined by competitive displacement of 3H-dihydrotestosterone using 64-24 rat mammary tumor cells. 2-Methoxyestradiol is the first example of a naturally occurring steroid which binds with high affinity to TeBG but with low affinity to both androgen and estrogen receptors.