Rumpel E, Michna H, Kühnel W
Institut für Anatomie, Medizinischen Universität zu Lübeck, Deutschland.
Ann Anat. 1993 Apr;175(2):141-9. doi: 10.1016/s0940-9602(11)80170-6.
The effects of long-term treatment with the progesterone antagonists ZK 98.299 and ZK 112.993 on the uterus of intact mature rats were investigated with light and electron microscopy. After 3-4 weeks treatment with both progesterone antagonists, the uterine luminal epithelium showed ongoing mitotic activity, increased apoptosis and invasion by granulocytes. Many uteri showed metaplastic areas with stratified squamous epithelium. Basically, the same changes occurred, but to a lesser extent, in the glandular epithelium. At the ultrastructural level, the epithelial cells displayed the morphological features of a certain degree of differentiation. The dissociation of collagen fibres, infiltration by granulocytes and dilatation of small vessels were observed in the subepithelial connective tissue. The myometrium increased in thickness and electron microscopic examination revealed hypertrophic myocytes with a well developed granular endoplasmic reticulum. Most of the morphological reactions may be regarded as due to the direct inhibitory action of progesterone antagonists at the level of the different uterine tissues and the resulting unopposed action of estrogen. The metaplastic changes and the suppression of the anti-proliferative action of progesterone on uterine epithelial cells should be taken into account when treating women in their reproductive years with these drugs for long periods of time, as may be necessary for the endocrine treatment of mammary cancer and endometriosis.
采用光镜和电镜研究了孕激素拮抗剂ZK 98.299和ZK 112.993对未切除卵巢的成熟大鼠子宫的长期作用。在用这两种孕激素拮抗剂治疗3 - 4周后，子宫腔上皮显示有持续的有丝分裂活性、凋亡增加以及粒细胞浸润。许多子宫出现了化生区域，有复层鳞状上皮。基本上，腺上皮也发生了同样的变化，但程度较轻。在超微结构水平上，上皮细胞表现出一定程度分化的形态特征。在皮下结缔组织中观察到胶原纤维解离、粒细胞浸润和小血管扩张。子宫肌层厚度增加，电镜检查显示肌细胞肥大，粗面内质网发达。大多数形态学反应可能被认为是由于孕激素拮抗剂在不同子宫组织水平上的直接抑制作用以及由此产生的雌激素无对抗作用。在对育龄妇女长期使用这些药物进行治疗时，如乳腺癌和子宫内膜异位症的内分泌治疗可能需要的那样，应考虑到化生变化以及孕激素对子宫上皮细胞抗增殖作用的抑制。
