Aloyz R, Vindrola O, Rodríguez Vida M I, Kleid M C, Finkielman S, Nahmod V E
Instituto de Investigaciones Médicas, Sección Sustancias Vasoactivas, Buenos Aires, Argentina.
Neuroendocrinology. 1992 Dec;56(6):788-96. doi: 10.1159/000126309.
We have previously found that proenkephalin processing is incomplete in the neonatal rat adrenal medulla and have postulated that immaturity of either the nervous input to the gland or the endocrine hypothalamus-pituitary-adrenal axis might be involved in the failure of the gland to yield free met-enkephalin. Therefore, we investigated whether cholinergic and glucocorticoid agonists may act in vivo on neonatal proenkephalin processing; reserpine, a strong activator of precursor cleavage, was also tested. Acute administration of nicotine, pilocarpine and reserpine to 24-hour-old rats increased the content of enkephalin-containing peptides (ECP) after 72 h (4-day-old rats) and activated the posttranslational processing of proenkephalin to high, intermediate and low molecular weight peptides respectively, although free met-enkephalin was not produced. Chronic treatment with nicotine and pilocarpine neither modified the concentration of ECP nor were able to induce free metenkephalin production. Chronic administration of dexamethasone increased ECP levels in the adrenal of 4-day-old rats and caused proenkephalin processing to intermediate- and low-molecular-weight products including the production of free met-enkephalin. These results indicate that only dexamethasone was able to induce the production of met-enkephalin in the adrenal of neonatal rats, suggesting an involvement of the hypothalamus-pituitary-adrenal axis in the proteolytic maturation of proenkephalin during the ontogeny of rat adrenal medulla.
我们之前发现新生大鼠肾上腺髓质中前脑啡肽的加工过程不完整，并推测腺体神经输入或内分泌下丘脑 - 垂体 - 肾上腺轴的不成熟可能与腺体无法产生游离甲硫脑啡肽有关。因此，我们研究了胆碱能和糖皮质激素激动剂在体内是否会作用于新生大鼠的前脑啡肽加工过程；还测试了利血平，一种前体裂解的强激活剂。对24小时龄大鼠急性给予尼古丁、毛果芸香碱和利血平，72小时后（4日龄大鼠）含脑啡肽肽（ECP）的含量增加，并且分别激活了前脑啡肽向高分子量、中分子量和低分子量肽的翻译后加工过程，尽管未产生游离甲硫脑啡肽。尼古丁和毛果芸香碱的慢性处理既未改变ECP的浓度，也无法诱导游离甲硫脑啡肽的产生。地塞米松的慢性给药增加了4日龄大鼠肾上腺中ECP的水平，并导致前脑啡肽加工为中分子量和低分子量产物，包括游离甲硫脑啡肽的产生。这些结果表明，只有地塞米松能够诱导新生大鼠肾上腺中甲硫脑啡肽的产生，提示下丘脑 - 垂体 - 肾上腺轴参与大鼠肾上腺髓质个体发育过程中前脑啡肽的蛋白水解成熟。
