Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice

F. J. Steyn, K. Lee, M. J. Fogarty, J. D. Veldhuis, P. A. McCombe, M. C. Bellingham, S. T. Ngo, C. Chen

Research output: Contribution to journalArticle

12 Scopus citations

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 hSOD1G93A mice throughout the course of ALS disease. Male wild-type and hSOD1G93A 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 hSOD1G93A 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 hSOD1G93A 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.

Original languageEnglish (US)
Pages (from-to)4695-4706
Number of pages12
JournalEndocrinology
Volume154
Issue number12
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Endocrinology

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    Steyn, F. J., Lee, K., Fogarty, M. J., Veldhuis, J. D., McCombe, P. A., Bellingham, M. C., Ngo, S. T., & Chen, C. (2013). Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice. Endocrinology, 154(12), 4695-4706. https://doi.org/10.1210/en.2013-1570