Differential effects of catechol estrogens, progestins and CI-628 administered by constant infusion on the central and peripheral action of estradiol.

By means of continuous infusion by Alzet minipumps, we tested the ability of the catechol estrogens, 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2), as well as two progestins and the anti-estrogen, CI-628, to block the action of estradiol (E2) on sexual behavior, LH surge frequency, uterine weight increase and glucose-6-phosphate dehydrogenase (G6PDH) activity in the uterus and pituitary of ovariectomized rats. Neither catechol estrogen produced inhibitory effects, whereas the potent progestin, R-5020 (5 micrograms/h), and CI-628 (50 micrograms/h) inhibited the E2-induced increase in the LH surge frequency and lordosis response. Progesterone at 20 micrograms/h and CI-628 at 5 micrograms/h did not influence these end points. In the pituitary and uterus, the concurrent administration of R-5020 and E2 attenuated the increase of G6PDH activity. As expected, CI-628 inhibited the action of E2 on G6PDH but was more effective in doing so at the lower of the two doses. CI-628 (50 micrograms/h) also blocked the neuroendocrine and behavioral effects of 2-OHE2 (1 microgram/h) and 4-hydroxyestradiol (0.1 microgram/h). Taken together with our previous studies, these results are consistent with the notion that the catechol estrogens exert effects on sexual behavior and LH surge frequency by virtue of their estrogenic properties rather than by other means.