Cousins R J, Dunn M A, Leinart A S, Yedinak K C, DiSilvestro R A
Am J Physiol. 1986 Dec;251(6 Pt 1):E688-94. doi: 10.1152/ajpendo.1986.251.6.E688.
Regulation of zinc metabolism by dibutyryl cAMP, glucagon, and epinephrine was examined in rats fed adequate amounts of zinc. Dibutyryl cAMP, epinephrine, and glucagon each produced an increase in liver metallothionein levels by 10 h after they were first administered. The increase in liver metallothionein was inversely related to the serum zinc concentration. Treatment with dexamethasone, a glucocorticoid, accentuated these effects to some extent. Both metallothionein I and II were induced by dibutyryl cAMP and glucagon. Levels of metallothionein mRNA in total liver RNA extracts were measured by dot blot hybridization using a synthetic 21-base oligonucleotide complimentary to the 5' region of both the metallothionein I and II genes. Individual administration of dibutyryl cAMP, glucagon, and epinephrine increased the number of metallothionein mRNA molecules per cell by up to fourfold. The data suggest that glucagon and epinephrine are primary regulators of metallothionein gene expression acting at least in part via cAMP. In adrenalectomized rats, glucagon, dibutyryl cAMP, and epinephrine had a less potent effect in terms of metallothionein induction and depression of serum zinc concentrations. These effects were largely restored when dexamethasone was also given. Collectively these data suggest that changes in zinc metabolism associated with acute stress involve coordinate regulation mediated by many factors, including glucocorticoids and cAMP.
在给予充足锌量的大鼠中，研究了二丁酰环磷腺苷（dibutyryl cAMP）、胰高血糖素和肾上腺素对锌代谢的调节作用。首次给予二丁酰环磷腺苷、肾上腺素和胰高血糖素后10小时，它们各自都使肝脏金属硫蛋白水平升高。肝脏金属硫蛋白的升高与血清锌浓度呈负相关。用糖皮质激素地塞米松治疗在一定程度上增强了这些作用。金属硫蛋白I和II均由二丁酰环磷腺苷和胰高血糖素诱导。使用与金属硫蛋白I和II基因5'区域互补的21碱基合成寡核苷酸，通过斑点印迹杂交法测量总肝RNA提取物中金属硫蛋白mRNA的水平。单独给予二丁酰环磷腺苷、胰高血糖素和肾上腺素可使每个细胞中金属硫蛋白mRNA分子的数量增加多达四倍。数据表明，胰高血糖素和肾上腺素是金属硫蛋白基因表达的主要调节因子，至少部分通过环磷腺苷发挥作用。在肾上腺切除的大鼠中，胰高血糖素、二丁酰环磷腺苷和肾上腺素在诱导金属硫蛋白和降低血清锌浓度方面的作用较弱。当同时给予地塞米松时，这些作用在很大程度上得以恢复。总体而言，这些数据表明与急性应激相关的锌代谢变化涉及由多种因素介导的协同调节，包括糖皮质激素和环磷腺苷。
