Pituitary, pancreatic and gut neuroendocrine defects in protein tyrosine phosphatase-sigma-deficient mice.
The expression of receptor protein tyrosine phosphatase sigma (PTPfinal sigma) is developmentally regulated in neuronal and neuroendocrine tissues. We have previously shown that mice deficient in PTPfinal sigma demonstrate nervous system abnormalities, pituitary hypoplasia, increased neonatal mortality (60%), and death from a wasting syndrome at 2-3 wk of age (38%). We have now examined the role of PTPfinal sigma on pituitary, pancreas and enteroendocrine cytodifferentiation, hormone production, and development. The adenohypophyses of PTPfinal sigma(-/-) mice were small and exhibited reduced GH and PRL immunoreactivity. Cells containing TSH, LH, FSH, ACTH, pituitary-specific POU homeodomain factor (Pit-1), ER, and steroidogenic factor 1 were found in normal proportions and distributions. The diminished expression of GH and PRL was not associated with apoptosis of somatotrophs or lactotrophs. Pit-1-positive TSH-negative cells were detected, suggesting that impaired GH and PRL synthesis was not attributable to Pit-1 deficiency. In the knockout mice, pancreatic islets were hypoplastic with reduced insulin immunoreactivity, and there was also variable expression of gut hormones. Functionally, the GH deficiency was associated with hypoglycemia and death in the PTPfinal sigma(-/-) neonate and accordingly, ip administration of GH rescued the PTPfinal sigma(-/-) neonate and normalized the blood glucose. These data indicate that PTPfinal sigma plays a major role in differentiation and development of the neuroendocrine system.
Batt
Jane
J
The Hospital for Sick Children, Program in Cell Biology, and Institute of Medical Science and Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
Asa
Sylvia
S
Fladd
Chris
C
Rotin
Daniela
D
D000818:Animals; D000831:Animals, Newborn; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D004064:Digestive System / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000002:abnormalities* / Q000473:pathology; D010179:Pancreas / Q000002:abnormalities* / Q000473:pathology; D010902:Pituitary Gland / Q000002:abnormalities* / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
D001639:Bicarbonates; D001786:Blood Glucose; D017027:Protein Tyrosine Phosphatases; C516885:Ptprs protein, mouse; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2