The study by Jensen et al. investigates the interaction of estradiol with rat uterus, revealing a two-step mechanism involving the formation of a 9.5S complex and a 5S complex. The 9.5S complex, which is extranuclear, facilitates the uptake of estradiol by uterine cells, while the 5S complex, formed from the 9.5S complex, is responsible for hormone retention and growth initiation. The 9.5S complex is not saturated even at hyperphysiological levels of estradiol, indicating its significant role in initial uptake. The 5S complex formation requires the presence of the 9.5S complex in the supernatant fraction, suggesting that estradiol must be presented to the nucleus in this form. The study also highlights the temperature-dependent nature of these processes and the potential involvement of an enzyme-catalyzed reaction in the transformation of the 9.5S complex into the 5S complex.The study by Jensen et al. investigates the interaction of estradiol with rat uterus, revealing a two-step mechanism involving the formation of a 9.5S complex and a 5S complex. The 9.5S complex, which is extranuclear, facilitates the uptake of estradiol by uterine cells, while the 5S complex, formed from the 9.5S complex, is responsible for hormone retention and growth initiation. The 9.5S complex is not saturated even at hyperphysiological levels of estradiol, indicating its significant role in initial uptake. The 5S complex formation requires the presence of the 9.5S complex in the supernatant fraction, suggesting that estradiol must be presented to the nucleus in this form. The study also highlights the temperature-dependent nature of these processes and the potential involvement of an enzyme-catalyzed reaction in the transformation of the 9.5S complex into the 5S complex.