Grunert G, Neumann G, Porcia M, Tchernitchin A N
Department of Experimental Morphology, University of Chile Medical School, Santiago.
Biol Reprod. 1987 Oct;37(3):527-38. doi: 10.1095/biolreprod37.3.527.
The present study was designed to investigate the dose-response of clomiphene on several estrogenic responses in the immature rat uterus and to compare it to available data on estradiol-17 beta. A dissociation was demonstrated among the different estrogenic responses induced by clomiphene. Very high doses of clomiphene were needed to induce the 6-h uterine eosinophilia and deep endometrial edema, and maximal response levels were not reached at any dose studied. On the contrary, many genomic responses were induced with much lower doses of clomiphene, and maximal response levels were reached with at least the two highest doses of clomiphene. This dissociation is in agreement with the existence of separate groups of responses that are mediated by multiple and independent mechanisms of estrogen action involving different kind of receptors. Luminal epithelial, glandular epithelial, and myometrial hypertrophies were also found to differ with regard to the dose needed to induce this response in each cell type. The dissociation between genomic responses of the different uterine cell types supports the hypothesis of different estrogen receptors for each kind of cell. Clomiphene induces mitoses in the different cell types, but the proportion of mitoses in the cell types was different from that described for estradiol. It is suggested that these differences are also due to differences between receptors involved in cell proliferation.
本研究旨在探讨克罗米芬对未成熟大鼠子宫几种雌激素反应的剂量反应，并将其与有关17β-雌二醇的现有数据进行比较。结果表明，克罗米芬诱导的不同雌激素反应之间存在分离现象。诱导6小时子宫嗜酸性粒细胞增多和深层子宫内膜水肿需要非常高剂量的克罗米芬，在所研究的任何剂量下均未达到最大反应水平。相反，较低剂量的克罗米芬即可诱导许多基因组反应，至少在克罗米芬的两个最高剂量时达到最大反应水平。这种分离现象与由涉及不同类型受体的多种独立雌激素作用机制介导的不同反应组的存在相一致。还发现，管腔上皮、腺上皮和子宫肌层肥大在每种细胞类型中诱导这种反应所需的剂量方面存在差异。不同子宫细胞类型的基因组反应之间的分离支持了每种细胞具有不同雌激素受体的假说。克罗米芬可诱导不同细胞类型发生有丝分裂，但不同细胞类型中有丝分裂的比例与雌二醇所描述的不同。提示这些差异也归因于参与细胞增殖的受体之间的差异。
