Partial Deletion of Pten in the Hypothalamus Leads to Growth Defects that Cannot be Rescued by Exogenous Growth Hormone

This is the authors' abstract. We don't add key points for this paper.

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.