Stachowiak M K, Lee P H, Rigual R J, Viveros O H, Hong J S
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Brain Res. 1988 Jun;427(3):263-73. doi: 10.1016/0169-328x(88)90049-6.
The effects of hypophysectomy (HPX) and dexamethasone (DEX) on the levels of Met5-enkephalin (ME), ME precursors, and the abundance of proenkephalin (pEK) mRNA, were examined in the adrenal medulla (AM) and superior cervical ganglia (SCG). To assess possible changes in enkephalin processing, both cryptic (after trypsin and carboxypeptidase B digestions) and native (without enzyme digestions) ME-like immunoreactivity (ME-LI) was measured. Three weeks after HPX the proportion of pEK mRNA to the total RNA content in the AM was not significantly changed when compared to sham-operated (SO) animals. Total (native + cryptic) ME-LI was decreased by 45% in the AM of HPX rats. This decrease was paralleled by a 58% depletion of AM proteins. Cryptic ME-LI was also reduced by 43%. In contrast, native ME-LI was not altered after HPX, indicating enhanced processing of ME precursors. Treatment with DEX (5 daily injections--1 mg/kg, i.p.) increased the relative abundance of pEK mRNA (+27%) and total ME-LI in the AM of HPX group, but not in SO group. Native ME-LI, cryptic ME-LI, and their ratio were not significantly affected by DEX in the AM of HPX or SO rats. In SCG, the relative abundance of pEK mRNA decreased by 25% after hypophysectomy. Total and cryptic ME-LI in the SCG of HPX rats were not changed when compared to SO rats. In contrast, HPX reduced native ME-LI suggesting decreased processing of ME precursors. Similarly, as in AM, DEX produced increase in the SCG pEK mRNA only in HPX (+68%) and not in the SO rats. In SCG, DEX produced decreases in total ME-LI which could be attributed to an increased enkephalin release. An overall reduction of cryptic ME-LI was also observed after DEX, whereas native ME-LI remained unchanged suggesting increased processing of enkephalins. Our findings indicate that the pituitary adrenocortical axis controls the relative proportions of ME to its precursors, and that this control involves both glucocorticoid-dependent (SCG) and glucocorticoid-independent (AM) mechanisms. In contrast, our studies do not suggest specific control of pEK synthesis by the pituitary adrenocortical axis. The pituitary adrenocortical axis may also influence the relative contents of ME and catecholamines in the AM and SCG. The ratio of ME/catecholamines increased after HPX (AM and SCG) and after DEX (SCG). Such regulation may contribute to the control of co-transmitter output in the sympathoadrenal system.
研究了垂体切除术（HPX）和地塞米松（DEX）对肾上腺髓质（AM）和颈上神经节（SCG）中Met5-脑啡肽（ME）水平、ME前体以及前脑啡肽（pEK）mRNA丰度的影响。为评估脑啡肽加工过程中可能的变化，同时检测了经胰蛋白酶和羧肽酶B消化后的隐蔽型（cryptic）以及未经酶消化的天然型（native）ME样免疫反应性（ME-LI）。与假手术（SO）动物相比，HPX术后三周，AM中pEK mRNA占总RNA含量的比例无显著变化。HPX大鼠AM中的总（天然型 + 隐蔽型）ME-LI降低了45%。这种降低与AM蛋白质减少58%平行。隐蔽型ME-LI也降低了43%。相反，HPX术后天然型ME-LI未改变，表明ME前体的加工增强。DEX处理（每日腹腔注射5次，1 mg/kg）使HPX组AM中pEK mRNA的相对丰度增加（+27%）以及总ME-LI增加，但SO组未出现此现象。在HPX或SO大鼠的AM中，DEX对天然型ME-LI、隐蔽型ME-LI及其比例均无显著影响。在SCG中，垂体切除术后pEK mRNA的相对丰度降低了25%。与SO大鼠相比，HPX大鼠SCG中的总ME-LI和隐蔽型ME-LI未改变。相反，HPX降低了天然型ME-LI，提示ME前体的加工减少。同样，与AM中情况类似，DEX仅使HPX大鼠（而非SO大鼠）的SCG中pEK mRNA增加（+68%）。在SCG中，DEX使总ME-LI降低，这可能归因于脑啡肽释放增加。DEX处理后还观察到隐蔽型ME-LI总体减少，而天然型ME-LI保持不变，提示脑啡肽加工增加。我们的研究结果表明，垂体-肾上腺皮质轴控制着ME与其前体的相对比例，且这种控制涉及糖皮质激素依赖性（SCG）和糖皮质激素非依赖性（AM）机制。相比之下，我们的研究未提示垂体-肾上腺皮质轴对pEK合成有特异性控制。垂体-肾上腺皮质轴也可能影响AM和SCG中ME与儿茶酚胺的相对含量。HPX术后（AM和SCG）以及DEX处理后（SCG），ME/儿茶酚胺的比例增加。这种调节可能有助于控制交感-肾上腺系统中共同递质的输出。
