Ignar-Trowbridge D M, Hughes A R, Putney J W, McLachlan J A, Korach K S
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Endocrinology. 1991 Nov;129(5):2423-30. doi: 10.1210/endo-129-5-2423.
The effect of estrogen on phosphoinositide (PI) metabolism was evaluated in the immature mouse uterus, a tissue which undergoes estrogen-induced proliferation. Uteri isolated from untreated mice or from mice injected ip with diethylstilbestrol (DES) were incubated with [3H]myo-inositol and assessed for incorporation of label into PI lipids or inositol phosphate generation. DES administration elicited a rapid increase in [3H]myo-inositol incorporation, which persisted until at least 18 h post treatment. This effect could not be duplicated by incubation of uteri with DES in vitro, although [3H]myo-inositol incorporation in uteri removed from DES-treated mice remained elevated for 3 h of in vitro incubation. Stimulation of PI lipid metabolism by DES was blocked by ICI 164,384, a specific estrogen receptor antagonist. The effect of DES on PI metabolism consisted of a time-dependent increase in the specific activity of both phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate and a significant increase of inositol (1,4,5)-trisphosphate mass by 12 h post treatment. These changes occur before the onset of estrogen-induced DNA synthesis. The results indicate that estrogens rapidly modulate PI lipid turnover through an estrogen receptor-mediated mechanism. Since the metabolic products of PI lipids are important for signal transduction and cellular proliferation, altered metabolism of these lipids may play an integral role in estrogen-induced mitogenesis.
雌激素对磷酸肌醇（PI）代谢的影响在未成熟小鼠子宫中进行了评估，该组织会经历雌激素诱导的增殖。从未经处理的小鼠或腹腔注射己烯雌酚（DES）的小鼠分离出的子宫，与[3H]肌醇一起孵育，并评估标记物掺入PI脂质或肌醇磷酸生成的情况。给予DES会导致[3H]肌醇掺入迅速增加，这种增加至少持续到处理后18小时。尽管从DES处理的小鼠中取出的子宫在体外孵育3小时后[3H]肌醇掺入仍保持升高，但在体外将子宫与DES一起孵育并不能重复这种效果。ICI 164,384（一种特异性雌激素受体拮抗剂）可阻断DES对PI脂质代谢的刺激。DES对PI代谢的影响包括磷脂酰肌醇-4-磷酸和磷脂酰肌醇-4,5-二磷酸的比活性随时间依赖性增加，以及处理后12小时肌醇（1,4,5）-三磷酸量显著增加。这些变化发生在雌激素诱导的DNA合成开始之前。结果表明，雌激素通过雌激素受体介导的机制快速调节PI脂质周转。由于PI脂质的代谢产物对信号转导和细胞增殖很重要，这些脂质代谢的改变可能在雌激素诱导的有丝分裂中起不可或缺的作用。
