King R A, Smith R M, Meller D J, Dahlenburg G W, Lineham J D
CSIRO (Australia), Division of Human Nutrition, Adelaide, South Australia.
J Endocrinol. 1988 Oct;119(1):117-25. doi: 10.1677/joe.0.1190117.
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)
在新生大鼠中,研究了生长激素(GH)和胰岛素样生长因子-I(生长调节素C)(IGF-I/SMC)缺乏在介导丙硫氧嘧啶(PTU)诱导的甲状腺功能减退对身体、骨骼生长及髓鞘形成影响方面的可能性。与正常动物或甲状腺功能正常的对照相比,PTU处理的母鼠所生幼崽的髓鞘形成(通过2',3'-环核苷酸3'-磷酸水解酶(CNP)活性评估)、骨骼生长(通过尾长评估)和体重均显著滞后。出生后20天,甲状腺功能减退动物的血浆GH检测不到(低于10微克/升),垂体GH含量为对照的1.2%,血浆、肝脏和肾脏IGF-I/SMC浓度分别为对照值的63%、68%和50%。甲状腺功能减退脑内的CNP活性为正常对照的52%,但IGF-I/SMC浓度为对照的113 - 154%。从第1天起用GH(每天10毫克/千克体重)治疗甲状腺功能减退动物,可使20天时肝脏和血浆IGF-I/SMC浓度恢复到高于正常动物和甲状腺功能正常对照的值。甲状腺功能减退肾脏中的IGF-I/SMC浓度也显著恢复(P<0.001)(为正常的79%),但脑内浓度未受影响。这些观察结果证明本实验中使用的GH治疗足以恢复缺乏状态。GH治疗对尾长或CNP活性无显著影响,对20天时的体重仅有轻微(4 - 24%)影响。只有甲状腺素能完全恢复体重,并大幅恢复尾长和CNP活性。(摘要截短于250字)