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

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Abstract

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.

Original languageEnglish
Pages (from-to)1015-1018
Number of pages4
JournalJournal of Endocrinological Investigation
Volume28
Issue number11
Publication statusPublished - 2005

Fingerprint

Corticotrophs
ACTH-Secreting Pituitary Adenoma
Pro-Opiomelanocortin
Mutation
Transcription Factors
Adrenocorticotropic Hormone
Messenger RNA
Genes
Pituitary ACTH Hypersecretion
Polymerase Chain Reaction
Introns
Nucleotides

Keywords

  • ACTH-secreting tumors
  • Cushing's disease
  • Gene expression
  • TPIT
  • Transcription factor

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "No mutations in TPIT, a corticotroph-specific gene, in human tumoral pituitary ACTH-secreting cells",
abstract = "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.",
keywords = "ACTH-secreting tumors, Cushing's disease, Gene expression, TPIT, Transcription factor",
author = "Bucciarelli, {L. G.} and Giraldi, {F. Pecori} and F. Cavagnini",
year = "2005",
language = "English",
volume = "28",
pages = "1015--1018",
journal = "Journal of Endocrinological Investigation",
issn = "0391-4097",
publisher = "Springer International Publishing",
number = "11",

}

TY - JOUR

T1 - No mutations in TPIT, a corticotroph-specific gene, in human tumoral pituitary ACTH-secreting cells

AU - Bucciarelli, L. G.

AU - Giraldi, F. Pecori

AU - Cavagnini, F.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - ACTH-secreting tumors

KW - Cushing's disease

KW - Gene expression

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KW - Transcription factor

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