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A thyrotrope-specific variant of Pit-1 transactivates the thyrotropin beta promoter.

Abstract
Thyrotropin (TSH) beta is a subunit of TSH, the expression of which is limited to the thyrotrope cells of the anterior pituitary gland. Tissue-specific expression of the mouse TSH beta gene is conferred by sequences between -270 and -80 of the 5'-flanking region. We have investigated tissue-specific expression of the TSH beta promoter in two thyrotrope-derived cell types: 1) TtT-97 thyrotropic tumors, which express the endogenous TSH beta gene, and 2) an alpha-TSH cell line, which was generated from a thyrotropic tumor that has lost the ability to express the TSH beta gene. The pituitary-specific transcription factor Pit-1 is present in thyrotropes and interacts with three cis-acting elements in the functionally important region of the TSH beta promoter. Pit-1 protein is present in TtT-97 tumor cells but is absent from alpha-TSH cells. Reintroduction of Pit-1 into alpha-TSH cells by transient transfection does not restore TSH beta promoter activity. We have identified an alternately spliced variant of Pit-1, called Pit-1T, the mRNA and protein expression of which is limited to thyrotrope-derived cells. Pit-1T contains a 14-amino acid insert in the transactivation domain due to an alternate 3' splice acceptor site. Transiently transfected Pit-1T increases TSH beta promoter activity in TtT-97 thyrotropic tumor cells, whereas additional Pit-1 has no effect. The alpha-TSH cell line, which lacks all Pit-1 proteins, requires both isoforms in order to stimulate TSH beta promoter activity. These data suggest that Pit-1T is a thyrotrope-specific splice variant of Pit-1 that is required for TSH beta promoter stimulation; furthermore, both Pit-1 and Pit-1T are required for TSH beta promoter activity in thyrotrope cells.
AuthorsB R Haugen, W M Wood, D F Gordon, E C Ridgway
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 268 Issue 28 Pg. 20818-24 (Oct 05 1993) ISSN: 0021-9258 [Print] United States
PMID8407911 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Pit1 protein, mouse
  • RNA, Messenger
  • Transcription Factor Pit-1
  • Transcription Factors
  • Thyrotropin
  • Ribonucleases
Topics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • Cells, Cultured
  • DNA, Single-Stranded
  • DNA-Binding Proteins (genetics, isolation & purification, metabolism)
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Messenger (metabolism)
  • Ribonucleases (metabolism)
  • Thyrotropin (genetics)
  • Transcription Factor Pit-1
  • Transcription Factors (genetics, isolation & purification, metabolism)
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured

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