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

Steyn, F. J., Lee, Kevin, Fogarty, M. J., Veldhuis, J. D., McCombe, P. A,, Bellingham, M. C., Ngo, S. T. and 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. doi:10.1210/en.2013-1570

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Author Steyn, F. J.
Lee, Kevin
Fogarty, M. J.
Veldhuis, J. D.
McCombe, P. A,
Bellingham, M. C.
Ngo, S. T.
Chen, C
Title Growth hormone secretion is correlated with neuromuscular innervation rather than motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2013-12-01
Year available 2013
Sub-type Article (original research)
DOI 10.1210/en.2013-1570
Open Access Status File (Author Post-print)
Volume 154
Issue 12
Start page 4695
End page 4706
Total pages 12
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
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.
Formatted 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.
Keyword Endocrinology & Metabolism
Endocrinology & Metabolism
ENDOCRINOLOGY & METABOLISM
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Tue, 03 Dec 2013, 22:46:59 EST by Dr Mark Bellingham on behalf of School of Biomedical Sciences