Endocrine Abstracts

Growth hormone releasing hormone (GHRH) is a neuropeptide mainly synthesised in the hypothalamus, known to exert a stimulatory effect on the synthesis and release of growth hormone (GH) from the pituitary via the activation of specific receptors. New data indicate that GHRH is also produced in both extrahypothalamic brain areas and in peripheral tissues. GHRH-receptor splice variants (SVs) have been found in several peripheral normal and neoplastic human tissues and mediate effects on cell proliferation and differentiation. At present, central non-endocrine effects of GHRH in extra-pituitary brain tissues have not yet been characterised. The aim of the present study was to investigate the effects of GHRH on cell survival in rat adult hippocampal progenitor cells (AHP) and to study the intracellular pathway involved. Cell viability was assessed by the Alamar blue assay. RT-PCR was performed to detect the presence of GHRH receptor mRNA. The results showed that GHRH receptor is expressed in AHP cells. GHRH dose dependently increased cell survival on AHP cells compared to control. After GHRH administration a significant increase of cAMP levels analyzed by ELISA was observed, suggesting a GHRH-induced activation of cAMP pathway. Consistently, western blot analysis showed a significant activation of Akt and ERK 1/2 survival pathway after GHRH administration. Activation of these signalling pathways preceded CREB phosphorylation, which plays an important role in the differentiation and maturation of newborn neurons in hippocampus. In conclusion, this study shows that GHRH has a protective effect on AHP cells. Moreover, in these cells GHRH is able to activate the cAMP-CREB pathway. Akt and ERK1/2 seem to be involved in this survival signalling. Thus, GHRH and its receptor may play an important role for hippocampal progenitor cells survival.