Growth Hormone Secretion Is Correlated With Neuromuscular Innervation Rather Than Motor Neuron Number in Early-Symptomatic Male Amyotrophic Lateral Sclerosis Mice
- 1 December 2013
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 154 (12), 4695-4706
- https://doi.org/10.1210/en.2013-1570
Abstract
GH deficiency is thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown benefit. To gain a better understanding of the role of GH secretion in ALS pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A) mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice were studied at the presymptomatic, onset, and end stages of disease. To assess the pathological features of disease, we measured motor neuron number and neuromuscular innervation. We report that GH secretion profile varies at different stages of disease progression in hSOD1(G93A) mice; compared with age-matched controls, GH secretion is unchanged prior to the onset of disease symptoms, elevated at the onset of disease symptoms, and reduced at the end stage of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is positively correlated with the percentage of neuromuscular innervation but not with motor neuron number. Moreover, this occurs in parallel with an elevation in the expression of muscle IGF-I relative to controls. Our data imply that increased GH secretion at symptom onset may be an endogenous endocrine response to increase the local production of muscle IGF-I to stimulate reinnervation of muscle, but that in the latter stages of disease this response no longer occurs.This publication has 64 references indexed in Scilit:
- Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALSNeuron, 2011
- A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDNeuron, 2011
- Analytical construct of reversible desensitization of pituitary-testicular signaling: illustrative application in agingAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2011
- Energy metabolism in amyotrophic lateral sclerosisThe Lancet Neurology, 2011
- Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in miceJCI Insight, 2010
- Hyperactive Intracellular Calcium Signaling Associated with Localized Mitochondrial Defects in Skeletal Muscle of an Animal Model of Amyotrophic Lateral SclerosisPublished by Elsevier BV ,2010
- Delivery of AAV-IGF-1 to the CNS Extends Survival in ALS Mice Through Modification of Aberrant Glial Cell ActivityMolecular Therapy, 2008
- Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALSBrain Research, 2007
- Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosisJournal of Lipid Research, 2007
- Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulationProceedings of the National Academy of Sciences of the United States of America, 2006