EXPRESSION PATTERNS OF MESSENGER RIBONUCLEIC-ACIDS ENCODING PROHORMONE CONVERTASES (PC2 AND PC3) IN HUMAN PITUITARY-ADENOMAS

OBJECTIVE Prohormone convertases (PC2 and PC3) have been reported to p lay an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been char acterized In human pituitaries. In addition, altered or insufficient p rohormone processing has been reported in some human pituitary adenoma s. Thus, the expression patterns of these mRNAs in non-tumorous and tu morous human pituitaries should be examined. DESIGN Total RNAs were ex tracted from non-tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression. SAMPLES Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non-functioning adenomas were obtained at surgery. Two non-tumorous pituitaries were also included in this study. MEASUREMENTS The contents were quantitati vely measured by Northern blot analysis using rat PC3 cDNA or human PC 2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products. RESULTS PC2 and PC3 mRNAs in non-tu morous samples were detected by Northern blot analysis whereas their c ontents in tumorous samples varied from high levels to undetectable. M arked variation of PC3 mRNA levels was observed among GH producing ade nomas. ACTH producing adenomas were observed to express PC3 mRNA. Nort hern blot analysis also revealed that PC2 mRNA levels in ACTH producin g adenomas were low except for one sample. PC2 mRNA expression in GH p roducing adenomas was confirmed by Southern blot analysis of RT-PCR pr oducts. This procedure also confirmed the various levels of PC2 mRNA e xpression among ACTH producing adenomas. CONCLUSION The expression of PC2 and PC3 mRNA In human pituitaries has been confirmed. However, the ir expression has been observed to vary quantitatively and not to be r estricted to certain types of pituitary cells.