Kraml J, Kolínská J, Kadlecová L, Zákostelecká M, Hirsová D, Schreiber V
First Department of Medical Chemistry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
J Steroid Biochem Mol Biol. 1995 Mar;52(3):251-7. doi: 10.1016/0960-0760(94)00171-h.
The antigestagen-antiglucocorticoid onapristone (ZK 98.299) was tested on three glucocorticoid-sensitive systems after hydrocortisone (HC) administration to suckling male rats, by determining onapristone (ZK)-induced inhibition of HC-provoked (1) increase of activities of intestinal brush-border enzymes, (2) desialylation of brush-border components and (3) thymolysis. HC acetate (75 mg/kg body weight (b.w.)) was injected s.c. on postnatal days 9 and 10, and ZK (150 mg/kg b.w.) on days 9, 10 and 11. The animals were killed on day 12 for assessing the early effect, or on days 15-17 for determining the delayed effect of HC and ZK. In all three systems the glucocorticoid effects were antagonized by ZK. The most sensitive to HC were systems 1 and 3, which exhibited both the early and the delayed effects. The most sensitive to the counteraction of ZK against administered HC was system 1, where HC was antagonized in both its early and delayed effects, whereas only delayed antagonistic action against administered HC was found in system 2. ZK alone had an early inhibitory effect on the activities of several brush-border enzymes and produced an early increase in thymus weight, accompanied by an increased DNA-protein ratio. No delayed effects of ZK alone on the three systems were observed.
在给雄性乳鼠注射氢化可的松（HC）后，通过测定孕三烯酮（ZK）诱导的对HC引发的以下三种糖皮质激素敏感系统的抑制作用，来测试抗孕激素-抗糖皮质激素药物孕三烯酮（ZK 98.299）：（1）肠刷状缘酶活性增加；（2）刷状缘成分去唾液酸化；（3）胸腺溶解。在出生后第9天和第10天皮下注射醋酸氢化可的松（75 mg/kg体重（b.w.）），在第9天、第10天和第11天注射ZK（150 mg/kg b.w.）。在第12天处死动物以评估早期效应，或在第15 - 17天处死以确定HC和ZK的延迟效应。在所有这三种系统中，糖皮质激素效应均被ZK拮抗。对HC最敏感的是系统1和3，它们表现出早期和延迟效应。对ZK拮抗所给予HC作用最敏感的是系统1，其中HC的早期和延迟效应均被拮抗，而在系统2中仅发现对所给予HC的延迟拮抗作用。单独使用ZK对几种刷状缘酶的活性有早期抑制作用，并使胸腺重量早期增加，同时伴有DNA - 蛋白质比率升高。未观察到单独使用ZK对这三种系统有延迟效应。
