Involvement of the pituitary-specific transcription factor pit-1 in somatolactotrope cell growth and death: an approach using dominant-negative pit-1 mutants

Mol Endocrinol. 2006 Dec;20(12):3212-27. doi: 10.1210/me.2006-0122. Epub 2006 Aug 10.


The anterior pituitary-specific transcription factor Pit-1 was initially identified and cloned as a transactivator of the prolactin (PRL) and GH genes and later as a regulator of the TSHb gene. It was found to be a major developmental regulator, because natural Pit-1 gene mutations cause a dwarf phenotype in mice and cause combined pituitary hormone deficiency associated with pituitary hypoplasia in humans. To further investigate the growth-promoting effects of Pit-1, we used a strategy based on the use of dominant-negative Pit-1 mutants as an alternative means of inactivating endogenous Pit-1 functions. R271W, a Pit-1 mutant identified in one allele in patients with severe combined pituitary hormone deficiency, and Pit-1Delta1-123, a deletion mutant in which only the DNA binding domain of Pit-1 is conserved, were generated, and their ability to abolish the effects of the endogenous native Pit-1 in the differentiated proliferating somatolactotrope GH4C1 cell line was investigated. Enforced expression of the dominant-negative mutants in GH4C1 cells using recombinant lentiviral vectors decreased the levels of expression of known Pit-1 target genes such as PRL and GH, abolished the hormone release, and reduced cell viability by decreasing the growth rate and inducing apoptosis via a caspase-independent pathway. These results show for the first time that the growth-promoting effects of Pit-1 are at least partly due to the fact that this transcription factor prevents apoptotic cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Cell Death / genetics
  • Cell Proliferation
  • Cells, Cultured
  • Dwarfism, Pituitary / genetics*
  • Gene Expression Regulation*
  • Gene Transfer Techniques
  • Humans
  • Lentivirus / genetics
  • Mutation
  • Pituitary Hormones / deficiency*
  • Pituitary Hormones / metabolism
  • Transcription Factor Pit-1 / genetics
  • Transcription Factor Pit-1 / physiology*
  • Transfection


  • Pituitary Hormones
  • Transcription Factor Pit-1