Ramos J G, Varayoud J, Kass L, Rodriguez H, Muñoz de Toro M, Montes G S, Luque E H
Department of Human Physiology, Faculty of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, C. C. 530, Paraje El Pozo, Ciudad Universitaria, 3000, Santa Fe, Argentina.
Steroids. 2000 Jul;65(7):409-14. doi: 10.1016/s0039-128x(00)00098-2.
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 17beta-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) 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 E(2) showed 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 invasion, 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 rise 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 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 E(2). Furthermore, the estrogen effect is blocked by P and this inhibition is reversed by RU-486.
大鼠子宫颈成熟涉及广泛的胶原溶解，其发生在嗜酸性粒细胞浸润之后。这些事件的激素控制尚不清楚。本研究的目的是探讨孕酮（P）和17β-雌二醇（E₂）调节嗜酸性粒细胞浸润的机制，并确定该事件是否由蛋白质合成介导。在妊娠后半期测量完整大鼠的子宫颈嗜酸性粒细胞浸润，并与用模拟妊娠水平剂量的P和E₂处理的去卵巢（O）假孕（PSP）大鼠的值进行比较。其他O-PSP大鼠用E₂拮抗剂（他莫昔芬）和抗孕激素RU-486处理。为了研究蛋白质合成在子宫颈嗜酸性粒细胞浸润中的作用，用放线菌素-D（mRNA合成抑制剂）处理大鼠，并在第21天或第22天处死动物以评估嗜酸性粒细胞浸润。用E₂处理的大鼠表现出高水平的浸润，他莫昔芬阻断了这种E₂效应。另一方面，P拮抗E₂对嗜酸性粒细胞浸润的刺激作用，然而，当用RU-486注射P和E₂处理的大鼠时，P的抑制作用被逆转。在完整的妊娠大鼠中，在血清P下降20小时后的第23天检测到嗜酸性粒细胞浸润急剧增加。最后，注射放线菌素-D的E₂处理大鼠没有嗜酸性粒细胞浸润。总之，雌激素引发的嗜酸性粒细胞浸润受经典雌激素受体拮抗剂他莫昔芬和mRNA合成阻滞剂放线菌素-D的影响，提示E₂的基因组作用。此外，雌激素作用被P阻断，这种抑制作用被RU-486逆转。
