Candidate genes for panhypopituitarism identified by gene expression profiling

Physiol Genomics. 2011 Oct 6;43(19):1105-16. doi: 10.1152/physiolgenomics.00080.2011. Epub 2011 Aug 9.


Mutations in the transcription factors PROP1 and PIT1 (POU1F1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. The dysmorphology of developing Prop1 mutant pituitaries readily distinguishes them from those of Pit1 mutants and normal mice. This and other features suggest that Prop1 controls the expression of genes besides Pit1 that are important for pituitary cell migration, survival, and differentiation. To identify genes involved in these processes we used microarray analysis of gene expression to compare pituitary RNA from newborn Prop1 and Pit1 mutants and wild-type littermates. Significant differences in gene expression were noted between each mutant and their normal littermates, as well as between Prop1 and Pit1 mutants. Otx2, a gene critical for normal eye and pituitary development in humans and mice, exhibited elevated expression specifically in Prop1 mutant pituitaries. We report the spatial and temporal regulation of Otx2 in normal mice and Prop1 mutants, and the results suggest Otx2 could influence pituitary development by affecting signaling from the ventral diencephalon and regulation of gene expression in Rathke's pouch. The discovery that Otx2 expression is affected by Prop1 deficiency provides support for our hypothesis that identifying molecular differences in mutants will contribute to understanding the molecular mechanisms that control pituitary organogenesis and lead to human pituitary disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gene Expression Profiling / methods*
  • Genotype
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Hypopituitarism / genetics
  • Hypopituitarism / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Otx Transcription Factors / genetics
  • Otx Transcription Factors / metabolism*
  • Polymerase Chain Reaction
  • Pregnancy
  • Transcription Factor Pit-1 / genetics
  • Transcription Factor Pit-1 / metabolism*


  • Homeodomain Proteins
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Pit1 protein, mouse
  • Prophet of Pit-1 protein
  • Transcription Factor Pit-1