THERAPUETIC APPLICATION OF AROMATASE INHIBITOR FOR LEIOMYOMA OF THE UTERUS AND ENDOMETRIOSIS

1. 子宫平滑肌瘤表达雌激素合成酶（芳香化酶）并原位合成雌激素。术前GnRH激动剂治疗除消除卵巢中的芳香化酶表达外，还消除平滑肌瘤组织中的原位芳香化酶表达。这种联合抑制可以解释为什么GnRH激动剂比自然绝经更迅速、更深刻地诱导平滑肌瘤收缩。添加雄烯二酮刺激培养的平滑肌瘤细胞增殖。这种生长刺激作用被芳香化酶抑制剂（法唑）预处理完全取消。口服法唑（1mg/kg/天，bbb10 1周）诱导大鼠无排卵状态。停药后1周内恢复发情周期。口服法德唑（2mg/天）诱导平滑肌瘤快速而深刻的消退，并解决围绝经期妇女的体积相关症状。阐述了芳香化酶抑制剂的潜在用途。AF-1/AD4BP结合最近端芳香化酶启动子（PII）的核半位点，上调子宫内膜异位症细胞芳香化酶的转录。因此，芳香化酶PII启动子的顺式元件在子宫内膜异位症和卵巢之间的调控存在很大差异，这表明芳香化酶的表达可能存在组织特异性和启动子特异性调节。

1. Leiomyoma of the uterus expresses estrogen synthetase (aromatase) and synthesize estrogen in situ. Preoperative GnRH agonist therapy abolishes aromatase expression in leiomyoma tissues in situ in addition to aromatase expression in the ovary. This combined suppression may explain why GnRH agonists induced shrinkage of leiomyoma more rapidly and more profoundly than natural menopause.2. Addition of androstenedione stimulates cell proliferation of leiomyoma cells in culture. This growth stimulatory action was completely canceled by the pretreatment with an aromatase inhibitor (fadrozole).3. Oral administration of fadrozole (1mg/kg/day,>1 weeks) induced anovulatory state in rats. Estrus cycles were recovered within 1 week after the discontinuation of fadrozole.4. Oral fadrozole (2mg/day) induced rapid and profound regression of leiomyoma and resolved bulk-related symptoms of a perimenopausal woman. The potential uses of aromatase inhibitors was demonstrated.5. AF-1/AD4BP binds to a nuclear half site of the most proximal promoter of aromatase (PII) and up-regulates the transcription of aromatase in endometriosis cells. Cis elements of PII promoter of aromatase, therefore its regulation, were quite different between endometriosis and the ovary, suggesting that tissues-specific and promoter-specific modulation of aromatase expression is possible.