Anovulation in female rats induced by neonatal administration of the catechol estrogens, 2-hydroxy-estradiol and 4-hydroxy-estradiol

The effects of estradiol (E2) and its 2- and 4-hydroxylated metabolites on gonadotrophin regulation in the female rat brain were examined. Neonatal female rats were injected from day 1 through 5 with E2, 2-OHE2 and 4-OHE2, at doses of 0.1, 1 and 10 micrograms/day. At 2, 6 and 24 h after the last estrogen injection, some animals from each treatment group were killed and the concentration of estrogen receptors (ERn) in their brain cell nuclei determined. The remaining animals were allowed to mature. Their vaginal smear patterns were examined from 7 to 9 and from 15 to 17 weeks of age. They were then ovariectomized and tested for their capacity to exhibit a luteinizing hormone (LH) surge in response to estrogen and progesterone injections. In a parallel series of experiments, the affinities of the three test estrogens for alpha-fetoprotein (AFP) were determined from in vitro competition studies with fetal rat serum. All three estrogens increased brain cell nuclear ERn concentrations, measured at 2 h after the final injection. E2 was more potent in this respect than either 4-OHE2 or 2-OHE2. E2 and 4-OHE2 competed for binding to AFP to an approximately equal extent. 2-OHE2, however, was a much weaker competitor for AFP than either of the other two compounds. The neonatal E2 and 4-OHE2 treatments reduced the number of animals showing regular cyclic vaginal smears, at all three doses tested. In contrast, 2-OHE2 significantly affected vaginal cyclicity only at a dose of 10 micrograms/day.(ABSTRACT TRUNCATED AT 250 WORDS)