Kinetic Study of 17α-Estradiol Activity in Comparison with 17β-Estradiol and 17α-Ethynylestradiol

17 alpha-estradiol (alpha E2), an endogenous stereoisomer of the hormone 17 beta-estradiol (E2), is capable of binding to estrogen receptors (ER). We aimed to mathematically describe, using experimental data, the possible interactions between alpha E2 and sperm ER during the process of sperm capacitation and to develop a kinetic model. The goal was to compare the suggested kinetic model with previously published results of ER interactions with E2 and 17 alpha-ethynylestradiol (EE2). The HPLC-MS/MS method was developed to monitor the changes of alpha E2 concentration during capacitation. The calculated relative concentrations B-t were used for kinetic analysis. Rate constants k and molar ratio n were optimized and used for the construction of theoretical B(t) curves. Modifications in alpha E2-ER interactions were discovered during comparison with models for E2 and EE2. These new interactions displayed autocatalytic formation of an unstable adduct between the hormone and the cytoplasmic receptors. alpha E2 accumulates between the plasma membrane lipid bilayer with increasing potential, and when the critical level is reached, alpha E2 penetrates through the inner layer of the plasma membrane into the cytoplasm. It then rapidly reacts with the ER and creates an unstable adduct. The revealed dynamics of alpha E2-ER action may contribute to understanding tissue rejuvenation and the cancer-related physiology of alpha E2 signaling.