Cell proliferation and vascularization in mouse models of pituitary hormone deficiency.
Mutations in the transcription factors PIT1 (pituitary transcription factor 1) and PROP1 (prophet of Pit1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. To determine the basis for this, we performed histological analysis of Pit1- and Prop1-deficient dwarf mouse pituitaries throughout fetal and postnatal development. Pit1-deficient mice first exhibit pituitary hypoplasia after birth, primarily caused by reduced cell proliferation, although there is some apoptosis. To determine whether altered development of the vascular system contributes to hypopituitarism, we examined vascularization from embryonic d 14.5 and throughout development. No obvious differences in vascularization are evident in developing Pit1-deficient pituitaries. In contrast, the Prop1-deficient mouse pituitaries are poorly vascularized and dysmorphic, with a striking elevation in apoptosis. At postnatal d 11, apoptosis-independent caspase-3 activation occurs in thyrotropes and somatotropes of normal but not mutant pituitaries. This suggests that Prop1 and/or Pit1 may be necessary for caspase-3 expression. These studies provide further insight as to the mechanisms of Prop1 and Pit1 action in mice.
Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor 48109-0618, USA.
Robert D
RD
Ward
Brandon M
BM
Stone
Lori T
LT
Raetzman
Sally A
SA
Camper
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010902:Pituitary Gland / Q000098:blood supply / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency*; D011247:Pregnancy; D050817:Transcription Factor Pit-1 / Q000172:deficiency / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D053148:Caspase 3; D020169:Caspases; D017931:DNA Primers; D018398:Homeodomain Proteins; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D042461:Vascular Endothelial Growth Factor A; C494185:Pou1f1 protein, mouse; C102134:Prophet of Pit-1 protein; C467480:vascular endothelial growth factor A, mouse; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse