| First Author | Choi D | Year | 2008 |
| Journal | Endocrinology | Volume | 149 |
| Issue | 9 | Pages | 4382-6 |
| PubMed ID | 18499759 | Mgi Jnum | J:145502 |
| Mgi Id | MGI:3834823 | Doi | 10.1210/en.2007-1761 |
| Citation | Choi D, et al. (2008) Partial deletion of Pten in the hypothalamus leads to growth defects that cannot be rescued by exogenous growth hormone. Endocrinology 149(9):4382-6 |
| abstractText | The GH/IGF-I axis plays a critical role in mammalian body growth. GH is secreted by the anterior pituitary, and its actions are primarily mediated by IGF-I that is secreted by the liver and other tissues. Local and circulating IGF-I action is largely mediated by the phosphoinositide 3-kinase signaling pathway, and phosphatase with tensin homology (PTEN) is a potent negative regulator of this pathway. Here we show that RIPcre+Ptenfl/fl mice, which exhibit PTEN deletion in insulin-transcribing neurons of the hypothalamus in addition to pancreatic beta-cells, result in a small-body phenotype that is associated with an unexpected increase in serum IGF-I levels. We tested whether exogenous GH can override the growth defect in RIPcre+Ptenfl/fl mice. Our results showed no significant difference in their growth between the RIPcre+Ptenfl/fl mice injected with GH or vehicle. Together, PTEN in the hypothalamic insulin-transcribing neurons plays an essential role in body size determination, and systemic GH cannot overcome the growth defect in these mice. |
