Time course of behavioral, physiological, and morphological changes after estradiol treatment of ovariectomized rats

Previous studies showed that treatment with 17-β-estradiol-3-benzoate (EB) reduces isoproterenol (ISOP) stimulated water intake by ovariectomized rats. This effect was observed 48h after the second of two EB injections, suggesting that the attenuation is attributable to classic EB actions to alter gene expression. However, in addition to classic, slowly-occurring, genomic effects, estrogens have more rapidly-occurring effects that may be nongenomic or 'nonclassical' genomic effects. Thus, it is possible that the EB attenuation of water intake stimulated by ISOP is genomic, nongenomic, or both. Accordingly, we measured ISOP-induced water intake by OVX rats at different times after EB injections, using time points likely to indicate classic genomic effects (48h or 24h) or nonclassical genomic or nongenomic effects (90min). We also examined EB effects on body weight, uterine weight, and plasma volume and Na⁺ concentration in the same animals using the same time points and EB dose. EB treatment decreased water intake stimulated by ISOP in both the 24-h and 48-h groups; however, water intake in the 90-min group was not affected by EB. Uterine weight was unchanged 90min after EB, but was increased 24h after the first injection of EB. In contrast, body weight decreased after EB, but not until 48h after the second EB injection. Finally, EB did not alter plasma Na⁺ concentration or hematocrit, though plasma protein concentration increased transiently 24h after EB treatment. Taken together, these findings suggest that the behavioral, morphological, and physiological effects of EB likely are attributable to slowly-occurring, classic genomic actions of estrogens. Moreover, the time course of the observed effects varied, suggesting tissue-specific differences in estrogen receptor density or subtype, or in co-activators or co-repressors that, ultimately, determine the timing and direction of EB effects.