TUMOR CELL SYNTHESIS AND SECRETION OF PEPTIDE HORMONES

这项研究的目的是阐明分子事件在 垂体和非垂体肿瘤细胞调节合成、储存、 和多肽激素的分泌，特别是来源于 来自前阿片皮质素(POMC)。我们检查了嗜铬细胞瘤 正常肾上腺髓质存在免疫反应(IR)-POMC 多肽与下丘脑肽促肾上腺皮质激素释放激素 促肾上腺皮质激素释放激素(CRH)，刺激脑垂体POMC的分泌。我们找到了所有的POMC 正常和肿瘤肾上腺髓质抽提物中的多肽。美国的ACTH 一例嗜铬细胞瘤完全具有生物学活性。我们还发现了大约 等量的完整CRH和Met21-O-CRH。完好无损的CRH是满的 生物活性。没有一例嗜铬细胞瘤患者有临床证据表明 异位促肾上腺皮质激素或促肾上腺皮质激素分泌。两国共存的重要意义 促肾上腺皮质激素释放激素对肾上腺髓质促肾上腺皮质激素释放的影响 脑垂体和肾上腺旁的POMC多肽的存在 皮质，其功能，帮助调节，仍有待阐明。 然而，我们的数据确实表明，ACTH的异位生产通过 肾上腺髓质肿瘤被称为“不适当的”更为恰当。我们 还测定了该菌POMC基因的cdna序列。 培养的人小细胞肺癌细胞系。795基本代码适用于所有 除了POMC的极端N末端。除了 保守的G-T碱基改变，序列与 人胎盘和胎肝基因组POMC DNA。Northern印迹 分析发现了两种大小约为1,300和 1,550个，相比之下，人类脑下垂体的mRNA为1,200个。.的存在 在另外三个基因中发现了较高分子量的POMC基因 非脑垂体瘤。这些数据表明，异位POMC和， 推测，其他异位荷尔蒙代表着不适当的表达 正常基因。然而，POMC的mRNA可能不完全或异常 在肿瘤细胞中加工。(C)

The objective of this research is elucidation of the molecular events in pituitary and nonpituitary tumor cells which regulate synthesis, storage, and secretion of polypeptide hormones, particularly, the hormones derived from pro-opiolipomelanocortin (POMC). We examined pheochromocytomas and normal adrenal medulla for the presence of immunoreactive (IR)-POMC peptides and the hypothalamic peptide, corticotropin-releasing hormone (CRH), that stimulates pituitary POMC secretion. We found all of the POMC peptides in normal and neoplastic adrenomedullary extracts. The ACTH in one pheochromocytoma was fully biologically active. We also found about equal parts of intact CRH and Met21-O-CRH. The intact CRH was full bioactive. None of pheochromocytoma patients had clinical evidence for ectopic ACTH or CRH production. The significance of the coexistence in the adrenal medulla of POMC peptides with CRH, their releasing hormone in the pituitary, and of the presence of POMC peptides adjacent to the adrenal cortex, whose function they help regulate, remains to be elucidated. However, our data do suggest that "ectopic" production of ACTH by adrenomedullary tumors is more appropriately termed "inappropriate." We have also determined the nucleotide sequence of cDNA to POMC mRNA from a cultured human small cell lung carcinoma line. The 795 bases code for all except the extreme N-terminus of POMC. With the exception of a conservative G-to-T base change, the sequence is identical to that of genomic POMC DNA from human placenta and fetal liver. Northern blot analysis reveals two mRNA species with approximate sizes of 1,300 and 1,550, as compared to 1,200 for human pituitary mRNA. The presence of higher molecular weight POMC mRNA has been noted in three other nonpituitary tumors. These data indicate that ectopic POMC and, presumably, other ectopic hormones represent inappropriate expression of normal genes. However, POMC mRNA may be incompletely or abnormally processed in tumor cells. (C)