DeBold C R, Menefee J K, Nicholson W E, Orth D N
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Mol Endocrinol. 1988 Sep;2(9):862-70. doi: 10.1210/mend-2-9-862.
Immunoreactive (IR) POMC peptides have been detected in several human nonpituitary tissues and most pheochromocytomas and lung cancers, including those not associated with ectopic ACTH syndrome. We found IR-ACTH, IR-gamma MSH, IR-beta-endorphin (beta END), and IR-lipotropin in extracts from the following 10 normal human tissues, listed in order of decreasing POMC peptide concentrations: adrenal, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, and duodenum. IR-ACTH, IR-gamma MSH, and IR-beta END were detected in all six pheochromocytomas and all 12 lung tumors (six squamous cell carcinomas, five adenocarcinomas, and one small cell carcinoma) we examined, as well as in a squamous cell carcinoma of the larynx. None of the patients had clinical evidence of ectopic ACTH syndrome. To determine whether these nonpituitary tissues and tumors actually synthesize POMC, rather than simply absorb POMC peptides from plasma, we examined poly(A) RNA prepared from these tissues and total RNA from pituitary by Northern blot hybridization for the presence of POMC-like mRNA with an exon 3 riboprobe. Pituitary contained a single POMC mRNA species of about 1150 bases. A short POMC-like mRNA of about 900 bases was found in all normal nonpituitary tissues, three of five pheochromocytomas, eight of nine lung cancers, and the laryngeal squamous cell tumor. In addition, larger POMC-like mRNA species between 1200 to 1500 bases were detected in adrenal, testis, ovary, placenta, two pheochromocytomas, and three squamous cell lung tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
在几种人类非垂体组织以及大多数嗜铬细胞瘤和肺癌中均检测到免疫反应性(IR)促肾上腺皮质激素原(POMC)肽,包括那些与异位促肾上腺皮质激素(ACTH)综合征无关的组织。我们在以下10种正常人类组织的提取物中发现了IR-ACTH、IR-γ促黑素(γ-MSH)、IR-β内啡肽(β-END)和IR-促脂素,按POMC肽浓度递减顺序排列为:肾上腺、睾丸、脾脏、肾脏、卵巢、肺、甲状腺、肝脏、结肠和十二指肠。在我们检测的所有6例嗜铬细胞瘤、所有12例肺肿瘤(6例鳞状细胞癌、5例腺癌和1例小细胞癌)以及1例喉鳞状细胞癌中均检测到IR-ACTH、IR-γ-MSH和IR-β-END。所有患者均无异位ACTH综合征的临床证据。为了确定这些非垂体组织和肿瘤是否实际合成POMC,而不是简单地从血浆中吸收POMC肽,我们通过Northern印迹杂交,用外显子3核糖探针检测从这些组织制备的聚腺苷酸(poly(A))RNA和垂体总RNA中是否存在POMC样mRNA。垂体含有一种约1150个碱基的单一POMC mRNA。在所有正常非垂体组织、5例嗜铬细胞瘤中的3例、9例肺癌中的8例以及喉鳞状细胞瘤中均发现了一种约900个碱基的短POMC样mRNA。此外,在肾上腺、睾丸、卵巢、胎盘、2例嗜铬细胞瘤和3例鳞状细胞肺癌中检测到1200至1500个碱基之间的较大POMC样mRNA。(摘要截短于250字)