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

Abstract

Ripening of the rat cervix involves widespread collagenolysis that follows an eosinophilic leukocyte infiltration. The hormonal control of these events is not well understood. The aims of this study were to investigate the mechanism through which progesterone (P) and 17β-estradiol (E2) 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 E2 in doses that mimicked the levels of pregnancy. Other O-PSP rats were treated with an E2 antagonist (tamoxifen) and the antiprogestin RU-486. To study the role of protein synthesis in eosinophilic invasion of the cervix, rats were treated with actinomycin-D (an inhibitor of mRNA synthesis), and animals were sacrificed on D21 or D22 to evaluate eosinophilic invasion. Rats treated with E2 showed high levels of infiltration and tamoxifen blocked this E2 effect. On the other hand, P antagonized the stimulatory effects of E2 on eosinophilic invasion, however when the P and E2 treated rats were injected with RU-486 the inhibitory effect of P was reversed. In intact pregnant rats a sharp rise in eosinophilic infiltration was detected on D23, 20 h after the fall of serum P. Finally, E2 treated rats injected with actinomycin-D had no invasion of eosinophils. In conclusion, the estrogen-triggered eosinophil invasion is affected by the classic estrogen receptor antagonist tamoxifen and by the mRNA synthesis blocker actinomycin-D suggesting a genomic action of E2. Furthermore, the estrogen effect is blocked by P and this inhibition is reversed by RU-486. Copyright (C) 2000 Elsevier Science Inc.