Dissociation of uterine eosinophilia and water imbibition from other estrogen-induced responses by nafoxidine pretreatment

We investigated the effect of pretreatment of immature rats with 5 or 50 micrograms nafoxidine (UA), or with 0.05 micrograms 17 beta-estradiol (E2) on several uterine responses elicited by treatment with a test injection of 15 micrograms E2, administered 48 h after pretreatment. Early (6 h) and late (24 h) responses were measured, including wet weight, RNA, protein and glycogen content and number of blood eosinophils per uterus. The results showed that, like a 24 h pretreatment with 5 micrograms UA, a 48 h pretreatment with either of the UA doses dissociated the early wet weight response from the late responses to E2 treatment, only the former being restored. In the case of E2 pretreatment, both types of response to E2 treatment were reinstalled. By contrast, uterine eosinophilia, induced 6 and 24 h after E2 treatment, was not only restored but even markedly amplified following any of the 3 pretreatments. This was obtained without amplification of the early wet weight response and with various levels of the other parameters at the time of administration of the test E2 injection (i.e. due to the pretreatment alone). From this it may be concluded that if the previously documented correlation between estrogen-induced eosinophilia and edema actually reflects the existence of a causal link between the 2 responses, as postulated by Tchernitchin in 1972, this would be with eosinophils controlling edema, rather than the reverse. Testable working hypotheses for the mechanism of amplification of the eosinophil response are proposed.