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Effect of growth hormone on growth and myelination in the neonatal hypothyroid rat
R A King1, R M Smith, D J Meller
1CSIRO (Australia), Division of Human Nutrition, Adelaide, South Australia.
Insights
Propylthiouracil-induced hypothyroidism in neonatal rats impaired growth and myelination. Growth hormone (GH) partially restored insulin-like growth factor-I (IGF-I) levels but did not improve growth or myelination, unlike thyroxine.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroscience
Background:
- Propylthiouracil (PTU) induces hypothyroidism in neonatal rats, impacting growth and development.
- Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are crucial for growth and myelination.
- The role of GH and IGF-I deficits in PTU-induced developmental impairments requires elucidation.
Purpose of the Study:
- To investigate the involvement of GH and IGF-I deficits in PTU-induced hypothyroidism's effects on neonatal rat growth and myelination.
- To assess the efficacy of GH treatment in restoring IGF-I levels and developmental parameters in hypothyroid rats.
Main Methods:
- Neonatal rats were exposed to PTU to induce hypothyroidism.
- Measurements included body weight, tail length, brain 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity, and plasma/tissue GH and IGF-I levels.
- GH treatment was administered to a subset of hypothyroid rats.
Main Results:
- PTU-induced hypothyroidism significantly retarded body weight, tail length, and brain CNP activity.
- Hypothyroid rats exhibited undetectable plasma GH and reduced pituitary GH content, with decreased IGF-I levels in plasma, liver, and kidney.
- GH treatment normalized IGF-I in plasma and liver but did not significantly improve growth or myelination; thyroxine administration was effective.
Conclusions:
- GH and IGF-I deficits contribute to PTU-induced hypothyroidism's impact on growth and myelination.
- GH treatment effectively restored IGF-I levels but was insufficient to reverse developmental deficits.
- Thyroxine is essential for fully restoring growth and myelination in this model of neonatal hypothyroidism.
Abstract:
The possible involvement of a deficit of GH and insulin-like growth factor-I (somatomedin C) (IGF-I/SMC) in mediating the effects of propylthiouracil (PTU)-induced hypothyroidism on body and skeletal growth and myelination was studied in the neonatal rat. Myelination (as assessed by 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity), skeletal growth (as assessed by tail length) and body weight of pups from PTU-treated mothers were significantly retarded compared with normal animals or euthyroid controls. At 20 days after birth, plasma GH in hypothyroid animals was undetectable (less than 10 micrograms/l), pituitary GH content was 1.2% of control, and plasma, liver and kidney IGF-I/SMC concentrations were 63, 68 and 50% of control values respectively. CNP activity in hypothyroid brain was 52% of normal controls but the concentration of IGF-I/SMC was 113-154% of control. Treatment of hypothyroid animals from day 1 with GH (10 mg/kg body weight per day) restored liver and plasma IGF-I/SMC concentrations at 20 days to values above those of normal animals and euthyroid controls. The concentration of IGF-I/SMC was also significantly (P less than 0.001) restored in hypothyroid kidney (79% of normal), but the concentration in brain was unaffected. These observations provide evidence that the GH treatment employed in the present experiments was adequate to restore the deficit. GH treatment had no significant effect on tail length or CNP activity, and only a small (4-24%) effect on body weight at 20 days. Only thyroxine was able fully to restore body weight and substantially restore tail length and CNP activity.(ABSTRACT TRUNCATED AT 250 WORDS)