Effect of growth hormone on growth and myelination in the neonatal hypothyroid rat

Abstract

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 (< 10 μg/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< 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. The present study provides strong evidence against an important involvement of GH or IGF-I/SMC in mediating the effects of thyroid hormone on myelination and body growth in the infant rat. It does not, however, rule out the possibility that thyroid hormone is required for the expression of the growth-promoting effects of IGF-I/SMC by other mechanisms such as the expression of the IGF-I/SMC receptor. J. Endocr. (1988) 119, 117–125