title: Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia.
abstract: A point mutation in the POU-specific portion of the human gene that encodes the tissue-specific POU-domain transcription factor, Pit-1, results in hypopituitarism, with deficiencies of growth hormone, prolactin, and thyroid-stimulating hormone. In two unrelated Dutch families, a mutation in Pit-1 that altered an alanine in the first putative alpha helix of the POU-specific domain to proline was observed. This mutation generated a protein capable of binding to DNA response elements but unable to effectively activate its known target genes, growth hormone and prolactin. The phenotype of the affected individuals suggests that the mutant Pit-1 protein is competent to initiate other programs of gene activation required for normal proliferation of somatotrope, lactotrope, and thyrotrope cell types. Thus, a mutation in the POU-specific domain of Pit-1 has a selective effect on a subset of Pit-1 target genes.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: R W
authors.initials: RW
authors.lastname: Pfäffle
authors.forename: G E
authors.initials: GE
authors.lastname: DiMattia
authors.forename: J S
authors.initials: JS
authors.lastname: Parks
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.forename: H
authors.initials: H
authors.lastname: Van der Nat
authors.forename: J L
authors.initials: JL
authors.lastname: Van den Brande
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: H A
authors.initials: HA
authors.lastname: Ingraham
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010903:Pituitary Gland, Anterior / Q000473:pathology*; D010907:Pituitary Hormones / Q000172:deficiency*; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000172:deficiency; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013972:Thyrotropin / Q000172:deficiency; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D010907:Pituitary Hormones; D011388:Prolactin; D013972:Thyrotropin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494187:POU1F1 protein, human; C494185:Pou1f1 protein, mouse; C494186:Pou1f1 protein, rat