Dose dependent modulation of receptor dynamics and uterine growth in immature rat by estradiol: importance of an additional nuclear binding at 24 hr for long-term (72 hr) uterine growth.

Abstract

Administration of a low dose of estradiol (0.25 or 2.5 microgram/animal) to immature rats caused a pulsatile receptor translocation, resulting in a single nuclear receptor peak (1-3 hr) and maintenance of the uterine growth until 24 hr. At a higher dose (10.0 microgram/rat), maintaining the circulatory estradiol levels for a longer duration, a biphasic nuclear translocation occurred. The usual profile of nuclear receptor binding until 12 hr was followed by a second phase of receptor translocation, resulting in an additional nuclear receptor peak at 24 hr. The uterus continued to grow until 72 hr, reaching five times its original wet weight. The duration of receptor interaction and the magnitude of uterine stimulation would, therefore, appear to be largely dependent upon the period of bioavailability of estradiol. However, there are additional intracellular regulatory mechanisms not fully understood as yet, which seem to modulate the cytosol-nuclear receptor dynamics, thus influencing the extent of uterine stimulation.