REVIEW ARTICLE Pituitary Transcription Factors: From Congenital Deficiencies to Gene Therapy M. H. Quentien,* A. Barlier,*  à J. L. Franc,* I. Pellegrini,* T. Brue*  à and A. Enjalbert*   *ICNE-UMR6544-CNRS-Universite ´ de la Me ´diterrane ´e, Institut Jean Roche, Marseille, France.   UF2683 Biologie Mole ´culaire, Service de Biochimie, Centre Hospitalo-Universitaire Conception, Marseille, France. à De ´partement d’Endocrinologie, Centre Hospitalo-Universitaire Timone, Marseille, France. The pituitary gland is an endocrine gland located immediately under the brain, in a sphenoid bone cavity called the sella turcica. This gland is composed of three lobes: (i) the anterior lobe (which con- stitutes the main part of the gland); (ii) the intermediate lobe (which is conserved in almost all species apart from humans at the postnatal stage); and (iii) the posterior lobe. The anterior and inter- mediate lobes are ectodermal derivatives, whereas the posterior lobe is of neuroectodermal origin. The anterior pituitary is defined by five cell types descending from a common population of progeni- tors: (i) lactotrophs, secreting prolactin (PRL); (ii) somatotrophs, pro- ducing growth hormone (GH); (iii) gonadotrophs, producing luteinising hormone (LH) and follicle stimulating hormone (FSH); (iv) thyrotrophs, producing thyroid-stimulating hormone (TSH); (v) and corticotrophs, producing adrenocorticotrophic hormone (ACTH). A sixth cell type consisting of the follicular stellate cells is present in the anterior pituitary, but the embryonic origin and function of these cells remain to be elucidated. The anterior pituitary plays a crucial role in homeostasic control in vertebrates. It serves as a central mediator of the information transmitted from the brain via the hypothalamus to peripheral endocrine organs such as the Journal of Neuroendocrinology Correspondence to: Dr Marie-Helene Quentien, Institut Jean Roche, Universite ´ de la Me ´diterrane ´e ) ICNE-UMR6544- CNRS, Faculte de Medecine Nord, bd Pierre Dramard, Marseille 13015, France (e-mail: quentien.m@jean-roche.univ-mrs.fr). Despite the existence of interspecies phenotypic variability, animal models have yielded valuable insights into human pituitary diseases. Studies on Snell and Jackson mice known to have growth hormone, prolactin and thyroid-stimulating hormone deficiencies involving the hypoplastic pitu- itary gland have led to identifying alterations of the pituitary specific POU homeodomain Pit-1 transcription factor gene. The human phenotype associated with rare mutations in this gene was found to be similar to that of these mice mutants. Terminal differentiation of lactotroph cells and direct regulation of the prolactin gene both require interactions between Pit-1 and cell type specific partners, including panpituitary transcriptional regulators such as Pitx1 and Pitx2. Synergistic activation of the prolactin promoter by Pitx factors and Pit-1 is involved not only in basal condition, but also in responsiveness to forskolin, thyrotrophin-releasing-hormone and epi- dermal growth factor. In corticotroph cells, Pitx1 interacts with Tpit. Tpit mutations have turned out to be the main molecular cause of neonatal isolated adrenocorticotrophin deficiency. This finding supports the idea that Tpit plays an essential role in the differentiation of the pro-opi- omelanocortin pituitary lineage. The effects of Pit-1 are not restricted to hormone gene regula- tion because this factor also contributes to cell division and protects the cell from programmed cell death. Lentiviral vectors expressing a Pit-1 dominant negative mutant induced time- and dose-dependent cell death in somatotroph and lactotroph adenomas in vitro. Gene transfer by lentiviral vectors should provide a promising step towards developing an efficient specific thera- peutic approach by which a gene therapy programme for treating human pituitary adenomas could be based. Key words: transcription factors, pituitary gland. doi: 10.1111/j.1365-2826.2006.01461.x Journal of Neuroendocrinology 18, 633–642 ª 2006 The Authors. Journal Compilation ª 2006 Blackwell Publishing Ltd