Endocrine Abstracts

Objective: Growth hormone (GH) has long been known to have neuroprotective properties. Hypophysectomy (Hx) completely abolishes circulating endocrine GH. Also neuronal (non-erythrocyte) haemoglobin beta chain (Hbb) in the hippocampus decreases following Hx while GH infusions and injections robustly increase the levels approximately 2-4-fold in male rat hippocampus. Recently it has been revealed that Hbb protein is present in mitochondria in the mammalian brain. Current investigations have shown that neuroprotective potential is associated with mitochondrial function. To investigate the signalling pathway between GH and Hbb, we measured the transcript levels of delta-aminolevulinate synthase 2 (ALAS2), a mitochondria specific rate-limiting enzyme of the heme synthesis in the hippocampus of male rats. To further extend our study of the signalling pathway involved in neuroprotection, we also included ALAS1 and hypoxia-inducible factor 1-alpha (HIF1a) in male rat hippocampus.

Methods & Results: GH was administered as a continuous infusion (GH inf) or as two daily injections (GHx2) in hx male rats. The response of ALAS2, ALAS1 and HIF1a to GH in the hippocampus was assessed by Q-RT-PCR. ALAS2 increased 3-fold in the male hippocampus and there was a significant difference in ALAS1 between Hx and GHx2 and between HIF1a and untreated hippocampus.

Conclusion: The type of GH administration affects Hbb abundance probably by increasing the level of ALAS2.