Induction of Delayed Implantation in Rats with Continuous but Not with Bolus Administration of Estriol1, 2

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Abstract
It has been suggested that estradiol-induced specific uterine protein is required for blastocyst implantation in laboratory rodents. Estriol has an anti-implantation effect which can be overcome by administration of estradiol. Recent data indicate, however, that the biological differences between estriol and estradiol are the result of the relatively short nuclear retention time of receptor-estriol complexes which can be overcome by repeated injections. To determine whether estriol administered repeatedly in small doses can be as effective as estradiol in inducing delayed nidation, several delayed implantation experiments in the rat have been performed. Termination of delayed implantation was observed in all oophorectomized, progesterone-treated rats following administration of 0.1 µg of estradiol in a single dose. Estriol, when administered as a single injection in doses ranging between 0.1 and 1.0 µg was significantly (P<0.01) less effective. However, if 0.8 µg of estriol was administered in eight divided doses over a period of 24 h, its effectiveness was comparable to that of estradiol. A similar implantation-promoting effect was achieved when estriol was released continuously from a s.c. capsule in a dose of 1.25 µg/24 h. When 1.0 µg of estriol was administered 1 h before 0.1 µg of estradiol was given, no antagonistic effect was observed. These data are consistent with recent reports indicating that the difference in biologic activity between estradiol and estriol is related to the brief nuclear retention time of the receptor-estriol complexes.