Objectives: 

We tried to elucidate, in vitro, the signaling pathways by which GH produces these effects on neurogenesis

Materials: 

NSC were obtained from the SGZ of 9d old mice and then plated on Corning dishes under proliferation conditions or differentiation medium.We first analysed whether in these cells there is GH and GH-R expression. The effects of the hormone in the presence or absence of selective inhibitors of GH signaling pathways were studied by using: Pegvisomant (20 ug/ml) to inhibit GH effect, SP600125(20 uM) to inhibit p-JNK, Rapamycin(20 nM) to inhibit mTor, and U0126(20 uM) to inhibit Erk.Apoptosis was evaluated by TUNEL, while proliferation was evaluated by BrdU incorporation (10 uM).Western blot were applied in differentiation conditions to evaluate protein levels in this conditions

Results: 

Neurospheres showed to have also GH and GH-R expression both in proliferation as differentiation conditions. Different cell populations expressed the GH and its receptor too. Adding GH (500 ng/ml) to a differentiation medium did not increase BrdU(10 uM) incorporation, as it did when the hormone was added under proliferation conditions. GH administration significantly decreased apoptosis in basal differentiation conditions.GH-signaling inhibitors significantly increased basal Apoptosis;this effect was reverted when GH was added, but not when added to SP600125-treated cells. Direct effect of GH was assesed adding Pegvisomant.GH only increased significantly Akt phosphorylation

Conclusions: 

By this study is demonstrated the presence of GH and its receptor in stem cells from SGZ of DG.Proliferation and apoptosis are perfectly explained with this results.Interestingly,all these pathways seems to be implicated in NSC survival,although it is clear that pErk is not implicated in GH pathway and p-JNK is the only pathway wich can not be reverted with GH treatment.Our results open a new way for investigating the effects of GH in CNS regenerative therapies, corroborating our pioneer results in human patients