Proopiomelanocortin Gene is Expressed in Many Normal Human Tissues and in Tumors not Associated with Ectopic Adrenocorticotropin Syndrome

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Abstract
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. The concentration of POMC-like mRNA was about 0.4% of pituitary level in testis and 0.008-0.08% in the other nonpituitary tissues, but the concentrations of the correspoding IR-POMC peptides were only 0.000003-0.00005% of pituitary levels. We conclude that the POMC gene is expressed in many normal tissues, as well as in pheochromocytomas and in malignant tumors of the lung and other tissues which are not associated with ectopic ACTH syndrome. It appears either that the smaller POMC-like mRNA in these tissues is not translated efficiently or that the POMC peptides are released or degraded much more rapidly in nonpituitary tissues than in the pituitary gland.