Fanidi A, Ahnadi C, Fayard J M, Pageaux J F, Laugier C
INSERM U 205, Laboratoire de Physiologie-Pharmacodynamie, Villeurbanne, France.
J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):571-7. doi: 10.1016/0960-0760(92)90386-w.
The ability of estradiol and tamoxifen to regulate cAMP levels and cAMP phosphodiesterase activities has been determined in the quail oviduct and in the mouse uterus. In the quail, tamoxifen (1 mg/kg daily for 3 days) had no effect on oviducal growth but significantly increased cAMP concentration (+49%). Injected concurrently with estradiol, tamoxifen completely inhibited oviduct growth as well as the increase of cAMP phosphodiesterase activity induced by the hormone alone and increased cAMP concentration (+229% over estradiol treated group). In the mouse, estradiol and tamoxifen displayed uterotrophic activity and increased cAMP phosphodiesterase activity. In both groups, cAMP concentration was greatly reduced (-76% in estradiol treated group; -86% in tamoxifen treated group). The opposite regulation of cAMP levels in the quail oviduct and the mouse uterus by tamoxifen reflected large differences in the contribution of calmodulin-dependent and -independent forms of phosphodiesterase to the hydrolysis of cAMP in the two models and the fact that tamoxifen stimulated the activity of the calmodulin-independent isoenzyme, while it competitively inhibited the activation of the calmodulin-dependent isoenzyme by calmodulin. Several lines of evidence strongly suggest that the regulation of cAMP levels is involved in growth-inhibiting or growth-promoting activity of tamoxifen.
已在鹌鹑输卵管和小鼠子宫中测定了雌二醇和他莫昔芬调节环磷酸腺苷（cAMP）水平及cAMP磷酸二酯酶活性的能力。在鹌鹑中，他莫昔芬（每日1 mg/kg，连续3天）对输卵管生长无影响，但显著提高了cAMP浓度（增加49%）。与雌二醇同时注射时，他莫昔芬完全抑制了输卵管生长以及单独激素诱导的cAMP磷酸二酯酶活性增加，并提高了cAMP浓度（比雌二醇处理组增加229%）。在小鼠中，雌二醇和他莫昔芬表现出子宫营养活性并增加了cAMP磷酸二酯酶活性。在两组中，cAMP浓度均大幅降低（雌二醇处理组降低76%；他莫昔芬处理组降低86%）。他莫昔芬对鹌鹑输卵管和小鼠子宫中cAMP水平的相反调节反映了两种模型中钙调蛋白依赖性和非依赖性磷酸二酯酶形式对cAMP水解的贡献存在巨大差异，以及他莫昔芬刺激非钙调蛋白依赖性同工酶的活性，同时竞争性抑制钙调蛋白依赖性同工酶被钙调蛋白激活的事实。几条证据有力地表明，cAMP水平的调节参与了他莫昔芬的生长抑制或生长促进活性。
