Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice

Meejeon Roh, Andrew J. Paterson, Sylvia L. Asa, Edward Chin, Jeffrey E. Kudlow

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) and its ligands EGF and transforming growth factor-α (TGFα) are expressed in the anterior pituitary, and overexpression of TGFα in the lactotrope cells of the pituitary gland in transgenic mice results in lactotrope hyperplasia and adenomata, suggesting a role for EGFR signaling in pituitary cell proliferation. To address the role of EGFR signaling in pituitary development in vivo, we blocked EGFR signaling in transgenic mice using the dominant negative properties of a mutant EGFR lacking an intracellular protein kinase domain (EGFR-tr). We directed EGFR-tr expression to GH- and PRLproducing cells using GH and PRL promoters, and a tetracycline-inducible gene expression system, to allow temporal control of gene expression. EGFR-tr overexpression in GH-producing cells during embryogenesis resulted in dwarf mice with pituitary hypoplasia. Both somatotrope and lactotrope development were blocked. However, when EGFR-tr overexpression was delayed to the postnatal period either by directing its expression with the PRL promoter or by delaying the onset of induction with tetracycline in the GH cells, no specific phenotype was observed. Lactotrope hyperplasia during pregnancy also occurred normally in the PRL-EGFR-tr mice. These data suggest that EGFR signaling is required for the differentiation and/or maintenance of somatomammotropes early in pituitary organogenesis but not later in life.

Original languageEnglish (US)
Pages (from-to)600-613
Number of pages14
JournalMolecular Endocrinology
Volume15
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

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Epidermal Growth Factor Receptor
Transgenic Mice
Transforming Growth Factors
Tetracycline
Hyperplasia
Gene Expression
Organogenesis
Pituitary Gland
Epidermal Growth Factor
Adenoma
Protein Kinases
Embryonic Development
Maintenance
Cell Proliferation
Ligands
Phenotype
Pregnancy

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Stage-sensitive blockade of pituitary somatomammotrope development by targeted expression of a dominant negative epidermal growth factor receptor in transgenic mice. / Roh, Meejeon; Paterson, Andrew J.; Asa, Sylvia L.; Chin, Edward; Kudlow, Jeffrey E.

In: Molecular Endocrinology, Vol. 15, No. 4, 01.01.2001, p. 600-613.

Research output: Contribution to journalArticle

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