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Accueil > Bibliographie > Involvement of the pituitary-specific transcription factor Pit-1 in (...)

Involvement of the pituitary-specific transcription (...)

Mol Endocrinol. 2006 Dec ;20(12):3212-27
Involvement of the pituitary-specific transcription factor Pit-1 in somatolactotrope cell growth and death : an approach using dominant-negative Pit-1 mutants.
Pellegrini I, Roche C, Quentien MH, Ferrand M, Gunz G, Thirion S, Bagnis C, Enjalbert A, Franc JL.

The anterior pituitary-specific transcription factor Pit-1 was initially identified and cloned as a transactivator of the PRL and GH genes, and later as a regulator of the TSHb gene. It was found to be a major developmental regulator, since natural Pit-1 gene mutations cause a dwarf phenotype in mice and combined pituitary hormone deficiency (CPHD) 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 negative dominant 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 CPHD 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.


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