Pituitary, Pancreatic and Gut Neuroendocrine Defects in Protein Tyrosine Phosphatase- Sigma-Deficient Mice

Abstract

Abstract The expression of receptor protein tyrosine phosphatase sigma (PTPσ) is developmentally regulated in neuronal and neuroendocrine tissues. We have previously shown that mice deficient in PTPσ 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 PTPσ on pituitary, pancreas and enteroendocrine cytodifferentiation, hormone production, and development. The adenohypophyses of PTPσ(−/−) 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 PTPσ(−/−) neonate and accordingly, ip administration of GH rescued the PTPσ(−/−) neonate and normalized the blood glucose. These data indicate that PTPσ plays a major role in differentiation and development of the neuroendocrine system.