No mutations in TPIT, a corticotroph-specific gene, in human tumoral pituitary ACTH-secreting cells

Background: TPIT is a recently identified transcription factor specific to proopiomelanocortin (POMC)-expressing cells within the pituitary and plays a pivotal role in the embryonal development of POMC lineage. As with other transcription factors, TPIT could theoretically also be involved in corticotroph adenomatous transformation and ACTH hypersecretion and published data indicate that TPIT is present in normal and adenomatous human corticotrophs. Objective: The aim of the present study was to corroborate this finding and to seek evidence for mutations in the TPIT coding sequence in human tumoral corticotrophs. Design and Methods: Eight human ACTH-secreting pituitary adenomas were collected during surgery, mRNA extracted from primary cultures and reverse transcribed. PCR was performed using 8 different sets of overlapping intron-spanning primers comprising the entire coding sequence of the gene and PCR products analyzed by sequencing. Results: TPIT mRNA was detected in all 8 ACTH-secreting pituitary adenomas without apparent mRNA variants. The entire coding sequence was accounted for, as attested by amplification with all sets of primers. Lastly, sequencing did not reveal differences in the nucleotide arrangement compared with the published sequence. Conclusions: Aberrant TPIT is unlikely to play a role in corticotroph tumoral trasformation, ie, Cushing's disease, as the entire coding sequence is expressed without any mutation by human pituitary ACTH-secreting adenomas. Conversely, the significance of this transcription factor in tumoral ACTH hypersecretion remains to be clarified.