Role of PROP1 in pituitary gland growth.
Mutations in the PROP1 transcription factor gene lead to reduced production of thyrotropin, GH, prolactin, and gonadotropins as well as to pituitary hypoplasia in adult humans and mice. Some PROP1-deficient patients initially exhibit pituitary hyperplasia that resolves to hypoplasia. To understand this feature and to explore the mechanism whereby PROP1 regulates anterior pituitary gland growth, we carried out longitudinal studies in normal and Prop1-deficient dwarf mice from early embryogenesis through adulthood, examining the volume of Rathke's pouch and its derivatives, the position and number of dividing cells, the rate of apoptosis, and cell migration by pulse labeling. The results suggest that anterior pituitary progenitors normally leave the perilumenal region of Rathke's pouch and migrate to form the anterior lobe as they differentiate. Some of the cells that seed the anterior lobe during organogenesis have proliferative potential, supporting the expansion of the anterior lobe after birth. Prop1-deficient fetal pituitaries are dysmorphic because mutant cells are retained in the perilumenal area and fail to differentiate. After birth, mutant pituitaries exhibit enhanced apoptosis and reduced proliferation, apparently because the mutant anterior lobe is not seeded with progenitors. These studies suggest a mechanism for Prop1 action and an explanation for some of the clinical findings in human patients.
Ward
Robert D
RD
Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109-0638, USA.
Raetzman
Lori T
LT
Suh
Hoonkyo
H
Stone
Brandon M
BM
Nasonkin
Igor O
IO
Camper
Sally A
SA
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D010902:Pituitary Gland / Q000166:cytology / Q000254:growth & development*; D010907:Pituitary Hormones / Q000378:metabolism; D016196:S Phase; D013234:Stem Cells; D013997:Time Factors
D018398:Homeodomain Proteins; D010907:Pituitary Hormones; C102134:Prophet of Pit-1 protein