Role of PROP1 in postnatal pituitary gland maturation.

Abstract

Mutations in the pituitary-specific transcription factor PROP1 are the most common, known cause of hypopituitarism in humans. Prop1 is the first pituitary-specific gene in the hierarchy of transcription factors that regulate pituitary development. It is essential for regulating the transition of pituitary stem cells to hormone-producing cells in an epithelial to mesenchymal-like transition process. It is also critical for activation of the lineage specific transcription factor POU1F1 in early organogenesis. Prop1 deficient mice have pituitary dysmorphology and lack the cells that produce growth hormone (GH), thyroid stimulating hormone (TSH), and prolactin (PRL). Prop1 is expressed in stem cells postnatally, but it is not known whether postnatal expression is necessary for completion of pituitary gland growth or organ maintenance. We tested whether PROP1 has a role in postnatal pituitary development by generating a conditional allele and deleting a crucial exon after birth. We determined that postnatal expression of Prop1 is important for appropriate expansion of the POU1F1 lineage and for robust expression of TSH, GH, and PRL in the early postnatal period. However, by 2 weeks of age, compensatory proliferation of committed POU1F1-expressing cells, but not SOX2-expressing stem cells, have normalized pituitary function. Thus, PROP1 appears to be dispensable after birth in mice.