Inhibition of the nuclear localization of [3H]estradiol in rat uterine tissue in vitro.

The temperature coefficient (Q10) for the nuclear-cytoplasmic intracellular distribution of specifically-bound [3H]estradiol is approximately 1.0 over the interval 10-30 degrees C. However, this value increases to 3.19 for the temperature influence upon the nuclear-cytoplasmic localization of hormone between 30 degrees and 37 degrees C. A Q10 value of this magnitude is indicative of a biological, rather than physical, translocation event. In assessment of a biological basis for translocation, several antimicrotubular/antimicrofilamentous agents were used alone and in combination to ascertain their effects upon in vitro nuclear localization of labeled estradiol in the uterus. The incubation of uterine tissue in D2O-Locke-Ringer's solution containing 10(-4) M colchicine or vinblastine significantly reduced the nuclear localization of [3H]estradiol to nonspecific retention. Tissue uptake of the hormone, cytoplasmic binding and retention of estrogen, and the nucleophilic property of the receptor-estrogen complex (REC) were unaffected. Other drug treatments were without effect upon nuclear occupancy of the REC. The apparent inhibition of translocation by the above regimen could be due to an alteration in cellular architecture incompatible with hormone movement or the result of a direct effect upon cellular components which impede the dynamic interactions of REC in nuclei of whole tissue. Although these results do not necessarily imply that a functional cytoskeleton is required for translocation, we suggest that the estrogen-mediated nuclear occupancy of REC is a biological process susceptible to disruption.