左旋18-甲基炔诺酮和米非司酮对分泌中期人子宫内膜HOXA11基因表达的影响

目的:通过口服孕激素类(左旋18-甲基炔诺酮,Levenorgestrel,LNG)和抗孕激素类(米非司酮,RU486)避孕药,研究孕激素对分泌中期人子宫内膜HOXA11基因表达的影响。方法:30名自愿者,于正常月经周期排卵后d7,刮取内膜组织做自身对照;实验周期在排卵前或排卵后2d,口服小剂量LNG(18例)或RU486(12例),同样在排卵后d7刮取内膜组织。用原位杂交方法检测服药子宫内膜HOXA11基因表达的变化。结果:对照组(分泌中期)内膜,间质细胞普遍表达HOXA11mRNA,而腺上皮HOXA11的表达则呈弱阳性或阴性。口服LNG后,子宫内膜形态变化不明显;内膜腺上皮HOXA11表达量进一步下降或无明显变化(即用药前后均表达阴性);间质细胞HOXA11表达增强。服用RU486后,内膜发育明显延迟,腺上皮HOXA11表达强度普遍大于对照组,而间质细胞的表达变化无明显规律。结论:孕激素对内膜腺上皮HOXA11基因的表达起负调控作用;正常分泌中期,内膜腺上皮HOXA11表达减弱或消失是内膜分化成熟的标志。

The Effect of Levenorgestrel and Mifepristone on HOXA11 Gene Expression in Human Endometrium

Objective:To investigate the effect of progesterone on HOXA11 gene expression in human endometri-um by oral administration of levenorgestrel (LNG) and mifepristone (RU486). Methods : Thirty healthy female volunteers with normal menstrual cycles were given a low dose of levenorgestrel or mifepristone pre- or post-ovulation. Endometrial biopsies in the control and treatment cycles were collected on the 7th day after the plasma luteinizing hormone (LH) surge. In situ hybridization was used to examine HOXA11 gene expression. Results:In the control group (midsecretory endometrium), HOXAll expression in stro-mal cells was strongly or moderately positive while it was weakly positive or negative in the glandular epithelium. After treatment of LNG, the expression increased in stromal cells, though no change in glandular epithelial expression was observed. After the oral intake of RU486, the endometrial development was delayed and HOXAll expression was increased in glandular cells, while it was not regular in stromal cells. Conclusion: Progesterone negatively regulates HOXAll gene expression in endometrial glandular epithelium, and the normal down-regulated expression of HOXAll gene in glandular epithelium at midsecretory phase is a sign of endometrial development and maturation.