Abstract

Thyroid deficiency (TD) in neonatal rats causes reduced growth of skeletal muscle that is disproportionately greater than that for other tissues (G. R. Adams, S. A. McCue, M. Zeng, and K. M. Baldwin. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 276: R954-R961, 1999). TD depresses plasma insulin-like growth factor I (IGF-I) levels, suggesting a mechanism for this effect. We hypothesized that TD and exposure to spaceflight (SF) would interact to reduce skeletal muscle growth via a reduction in IGF-I levels. Neonatal rats were flown in space for 16 days. There was a similar, nonadditive reduction in the growth of the body ( approximately 50%) and muscle weight (fast muscles, approximately 60%) with either TD or SF. In the soleus muscle, either SF or TD alone resulted in growth reductions that were augmented by SF-TD interactions. There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight. These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. The impact of these perturbations on skeletal muscle growth is relatively greater than the effect on somatic growth. The mechanisms by which either TD or SF impact growth appear to have a common pathway involving the control of plasma and muscle IGF-I concentrations.

Highlights

  • IntroductionThere were strong correlations between 1) muscle mass and muscle insulin-like growth factor I (IGF-I) levels and 2) circulating IGF-I and body weight

  • It has not been clear how these various growth-regulating mechanisms are impacted by environmental stimuli such as the weight-bearing activity of neonates

  • A number of studies have found that thyroid hormone levels are increasing during the early postpartum time period [13, 20, 26, 30], and experimental evidence indicates that this process is important for the regulation of both general and muscle-specific growth and maturation (e.g., Refs. 16, 24, 25)

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Summary

Introduction

There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. During this time, growth-related signals such as thyroid hormone levels are increasing to coordinate both growth and the maturation process [13, 20, 24, 26, 30]. IGF-I is thought to mediate many of the physiological effects of GH [15], and disruption of the IGF-I axis during critical developmental periods appears to have powerful effects on processes related to growth and development

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