Regulated endocrine-specific protein-18: a short-lived novel glucocorticoid-regulated endocrine protein.
Regulated endocrine-specific protein-18: a short-lived novel glucocorticoid-regulated endocrine protein.
复制标题
DOI：
10.1210/endo.135.6.7988462
复制
发表时间：
1994-12
期刊：
影响因子：
4.8
通讯作者：
B. Bloomquist;D N Darlington;G P Mueller;R. Mains;B. Eipper
中科院分区：
文献类型：
--
作者：
B. Bloomquist;D N Darlington;G P Mueller;R. Mains;B. Eipper
调节内分泌特异蛋白-18(RESP18)是一种18kodalton的内分泌特异转录本，在不同组织中的表达受多种不同的生理和药物刺激的调节。RESP18信使RNA存在于垂体前叶的所有细胞类型中，从最低的(促肾上腺皮质激素和促甲状腺激素)到最高的(促性腺激素、生长激素和促巨噬细胞)的水平变化了2倍；中间垂体的促黑素细胞的RESP18信使RNA水平与垂体前叶细胞中的最高水平相当。克隆了小鼠RESP18，并以此为基础在AtT-20细胞中进行了RESP18的生物合成研究，小鼠RESP18与大鼠RESP18有很高的同源性。脉冲追逐生物合成标记研究表明，ATT-20细胞表达的RESP18远低于内源激素前体POMC，但糖皮质激素处理降低了POMC，提高了RESP18的生物合成速率，使其接近等摩尔。令人惊讶的是，RESP18没有被显著地加工成更小的多肽，也没有分泌RESP18或任何更小的多肽。新合成的RESP18通常从ATT-20细胞提取物中消失，半衰期小于15min；糖皮质激素处理后，RESP18的细胞内半衰期显著增加。亚细胞分级后，发现RESP18完全是颗粒状的，并与内质网的标记物共分，而不是与分泌颗粒的标记物，如POMC和激素前处理酶。因此，RESP18是促肾上腺皮质激素分泌途径中的主要糖皮质激素反应蛋白，但其功能可能完全在神经内分泌细胞内。
Regulated endocrine-specific protein-18 (RESP18) is an 18-kilodalton endocrine-specific transcript whose expression is regulated by a number of different physiological and pharmacological stimuli in different tissues. RESP18 messenger RNA was identified in all cell types in the anterior pituitary, at levels that varied 2-fold from the lowest (corticotropes and thyrotropes) to the highest (gonadotropes, somatotropes, and mammotropes); the melanotropes of the intermediate pituitary have levels of RESP18 messenger RNA comparable to the highest levels in cells in the anterior pituitary. Mouse RESP18 was cloned and used as the basis for biosynthetic studies on RESP18 in AtT-20 cells, which express RESP18 endogenously; mouse RESP18 was highly homologous to rat RESP18. Pulse-chase biosynthetic labeling studies showed that AtT-20 cells expressed much less RESP18 than the endogenous prohormone, POMC, but that glucocorticoid treatment lowered POMC and raised RESP18 biosynthetic rates so that they were nearly equimolar. Surprisingly, RESP18 was not processed to smaller peptides to any significant extent, nor was RESP18 or any smaller peptide secreted. Newly synthesized RESP18 normally disappeared from AtT-20 cell extracts with a half-life of less than 15 min; the intracellular half-life of RESP18 was increased strikingly after glucocorticoid treatment of the cells. Upon subcellular fractionation, RESP18 was found to be entirely particulate and to cofractionate with markers for the endoplasmic reticulum, rather than with markers for secretory granules, such as POMC and prohormone-processing enzymes. Therefore, RESP18 is a major glucocorticoid-responsive protein in the secretory pathway of corticotropes, but its function may be entirely within the neuroendocrine cell.