The role of transcription factors implicated in anterior pituitary development in the aetiology of congenital hypopituitarism.
The anterior pituitary gland is a central regulator of growth, reproduction and homeostasis, and is the end-product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors leading to the development of this complex organ secreting six hormones from five different cell types. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1FI, LHX3, LHX4, TBX19 (TPIT), SOX3 and SOX2. The expression pattern of these transcription factors, their interaction with co-factors and their impact on target genes dictate the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia (SOD) and holoprosencephaly. Since mutations in any one transcription factor are uncommon, and since the overall incidence of mutations in known transcription factors is low in patients with CPHD, it is clear that many genes remain to be identified, and characterization of these will further elucidate the pathogenesis of these complex conditions, and also shed light on normal pituitary development.
Kelberman
Daniel
D
Biochemistry, Endocrinology and Metabolism Unit, Institute for Child Health, London, UK.
Dattani
Mehul T
MT
D000818:Animals; D041321:Chromosomes, Human, X / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D024002:HMGB Proteins / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007018:Hypopituitarism / Q000151:congenital* / Q000235:genetics*; D007031:Hypothalamus / Q000254:growth & development; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010903:Pituitary Gland, Anterior / Q000254:growth & development; D055748:SOXB1 Transcription Factors; D020825:T-Box Domain Proteins / Q000235:genetics; D050817:Transcription Factor Pit-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000075746:Zinc Finger Protein Gli2; D000097577:Homeobox Protein PITX2
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D060850:LIM-Homeodomain Proteins; D009687:Nuclear Proteins; D055748:SOXB1 Transcription Factors; D020825:T-Box Domain Proteins; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; D000097577:Homeobox Protein PITX2; C082593:GLI2 protein, human; C489736:HESX1 protein, human; C486362:LHX4 protein, human; C094898:Lhx3 protein; C494187:POU1F1 protein, human; C102134:Prophet of Pit-1 protein; C509239:SHH protein, human; C527782:SOX2 protein, human; C527785:SOX3 protein, human; C486589:TBX19 protein, human