Estrogen and progesterone modulation of eosinophilic infiltration of the rat uterine cervix

Ripening of the rat cervix involves widespread collagenolysis that follows an eosinophilic leukocyte infiltration. The hormonal control of these event s is not well understood. The aims of this study were to investigate the me chanism through which progesterone (P) and 17 beta-estradiol (E-2) modulate eosinophilic invasion and to determine if this event is protein synthesis mediated. Cervical eosinophilic invasion was measured in intact rats during the second half of pregnancy and compared with values from ovariectomized (O) pseudopregnant (PSP) rats treated with P and E-2 in doses that mimicked the levels of pregnancy. Other O-PSP rats were treated with an E-2 antagon ist (tamoxifen) and the antiprogestin RU-486. To study the role of protein synthesis in eosinophilic invasion of the cervix, rats were treated with ac tinomycin-D (an inhibitor of mRNA synthesis), and animals were sacrificed o n D21 or D22 to evaluate eosinophilic invasion. Rats treated with E-2 showe d high levels of infiltration and tamoxifen blocked this E-2 effect. On the other hand, P antagonized the stimulatory effects of E-2 on eosinophilic i nvasion, however when the P and E-2 treated rats were injected with RU-486 the inhibitory effect of P was reversed. In intact pregnant rats a sharp ri se in eosinophilic infiltration was detected on D23, 20 h after the fall of serum P. Finally, E-2 treated rats injected with actinomycin-D had no inva sion of eosinophils. In conclusion, the estrogen-triggered eosinophil invas ion is affected by the classic estrogen receptor antagonist tamoxifen and b y the mRNA synthesis blocker actinomycin-D suggesting a genomic action of E -2. Furthermore, the estrogen effect is blocked by P and this inhibition is reversed by RU-486. (C) 2000 Elsevier Science Inc. All rights reserved.