Estrogen Receptor Activation and the Dissociation Kinetics of Estradiol, Estriol, and Estrone*

The relationship among estrogen binding to the receptor of hormones of differing biological activities was investigated using estradiol, estriol, estrone, and the calf uterine estrogen receptor. For the three estrogens with different biological activities several kinetic parameters were similar. The association rate constants (k+1) at 25 C were 0.9–1.1 × 108 m−1 min−1. The rate constants of receptor activation (kact) were 2.1-3.1 × 107 m−1 min−1. The equilibrium association constants (Ka) at 0 C were: estradiol, 5.9 × 109 m−1; estriol, 3.8 × 109 m−1; and estrone, 1.3 × 109 m−1 (less than a 5-fold difference exists between estradiol and estrone). The dissociation rate constants were the only parameters distinguishing the three estrogens. The dissociation of estradiol and estriol from the estrogen receptor occurs in two exponential phases: the faster phase (k−1) from the nonactivated state of the receptor and the slower phase (k−2) from the activated state. Estrone dissociation from the receptor occurs as a...