In order to assess the mechanisms of
proopiomelanocortin (
POMC) gene expression in human
ACTH-producing
tumors, we performed the simultaneous evaluation of
POMC products and
messenger RNA (
mRNA) in tissue fragments obtained from two corticotropic
adenomas, five nonpituitary
tumors, and two normal human pituitaries. The
POMC products were examined using a combination of gel exclusion chromatography and four different radioimmunoassays directed against gamma 3
melanocyte stimulating hormone (gamma 3MSH),
ACTH,
gamma-lipotropin (
gamma LPH), and
beta-endorphin. The POMCmRNA was detected and analyzed by dot and northern blot hybridization using a single-stranded genomic
DNA probe corresponding to the coding region of the human
POMC gene. Tissue concentrations of
POMC products and
mRNA showed parallel distributions. Immunoreactive gamma 3MSH and
gamma LPH patterns revealed only 16-kD fragment- and
gamma LPH-like
peptides in normal and tumoral pituitaries; additional gamma 3MSH- and/or
beta MSH-like
peptides were found in all five nonpituitary
tumors. A single POMCmRNA of approximately 1,200 bases (b) was detected in normal and tumoral pituitaries; a single identical POMCmRNA was also found in four nonpituitary
tumors. A thymic
carcinoid tumor, in addition to the 1,200-b POMCmRNA, contained equal amounts of a second larger POMCmRNA of approximately 1,450 b. It is concluded that
POMC gene expression appears qualitatively unaltered in corticotropic
adenomas. In nonpituitary
tumors, in contrast, abnormal
POMC processing is frequent; in addition, an extra POMCmRNA was detected in a
thymic tumor with a greater length than the normal
mRNA; the mechanisms and pathophysiological implications of these modifications remain to be elucidated.