This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 20/12/3212    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pellegrini, I. Articles by Franc, J.-L. Search for Related Content PubMed PubMed Citation Articles by Pellegrini, I. Articles by Franc, J.-L.

Involvement of the Pituitary-Specific Transcription Factor Pit-1 in Somatolactotrope Cell Growth and Death: An Approach Using Dominant-Negative Pit-1 Mutants

Laboratoire Interactions Cellulaires Neuroendocriniennes (I.P., C.R., M.-H.Q, M.F., G.G., S.T., A.E., J.-L.F.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 6544-Université de la Méditerranée, Marseille, France; and Département de Thérapie Cellulaire et Génique (C.B.), Etablissement Français du Sang Alpes Méditerranée, Marseille, France

Address all correspondence and requests for reprints to: Dr. Jean-Louis Franc, Laboratoire Interactions Cellulaires Neuroendocriniennes, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6544, Université de la Méditerranée, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Boulevard P. Dramard, 13916 Marseille cedex 20, France. E-mail: franc.jl{at}jean-roche.univ-mrs.fr.

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-11-123, 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.

This article has been cited by other articles:

				D. Romano, K. Magalon, M. Pertuit, R. Rasolonjanahary, A. Barlier, A. Enjalbert, and C. Gerard Conditional Overexpression of the Wild-Type Gs{alpha} as the gsp Oncogene Initiates Chronic Extracellularly Regulated Kinase 1/2 Activation and Hormone Hypersecretion in Pituitary Cell Lines Endocrinology, June 1, 2007; 148(6): 2973 - 2983. [Abstract] [Full Text] [PDF]