Stephan D A, Menon R K, Franz B, Sperling M A
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213.
J Dev Physiol. 1993 Jun;19(6):241-6.
To investigate the role of thyroid hormone in the expression of the gene encoding the growth hormone receptor (GHR) and growth hormone binding protein (GHBP), fetal rats were made hypothyroid through the administration of the goitrogen methimazole to the mother. Euthyroidism was maintained in the mother by concurrent administration of L-thyroxine, which crosses the placenta poorly. Methimazole and L-thyroxine were continued in the mothers until weaning. After birth, groups of methimazole-treated or control pups were sacrificed immediately and at one, two, three, four, five, or six weeks after birth. In each group, weight was recorded, blood was obtained for measurement of T4, thyroid stimulating hormone (TSH), and growth hormone (GH), and liver tissue was obtained for quantitation of GHR and GHBP mRNA. The methimazole-treated pups were demonstrated to be hypothyroid, with markedly higher TSH and lower T4 concentrations, until weaning occurred between weeks three and four, after which they transiently became hyperthyroid at week five (T4 = 17 +/- 5 micrograms/dL vs. 6 +/- 0.5 micrograms/dL for controls) but returned to an euthyroid state at week six. In control pups the relative abundance of GHR and GHBP mRNA increased abruptly in week one, and increased three to four fold over the ensuing six weeks. Immediately after birth, the hypothyroid pups expressed significantly more GHR and GHBP mRNA than did the controls (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
为研究甲状腺激素在生长激素受体(GHR)和生长激素结合蛋白(GHBP)编码基因表达中的作用,通过给孕鼠注射致甲状腺肿药物甲巯咪唑,使胎鼠甲状腺功能减退。同时给孕鼠注射左旋甲状腺素以维持其甲状腺功能正常,左旋甲状腺素透过胎盘的能力较差。甲巯咪唑和左旋甲状腺素持续给予孕鼠直至幼鼠断奶。出生后,将甲巯咪唑处理组或对照组幼鼠在出生后即刻及出生后1、2、3、4、5或6周处死。每组记录体重,取血测定T4、促甲状腺激素(TSH)和生长激素(GH),取肝组织定量GHR和GHBP mRNA。结果显示,甲巯咪唑处理组幼鼠在断奶前(第3至4周)甲状腺功能减退,TSH浓度显著升高,T4浓度降低,断奶后第5周短暂出现甲状腺功能亢进(T4 = 17±5微克/分升,而对照组为6±0.5微克/分升),但在第6周恢复至甲状腺功能正常状态。对照组幼鼠GHR和GHBP mRNA的相对丰度在第1周突然增加,并在随后6周内增加3至4倍。出生后即刻,甲状腺功能减退幼鼠表达的GHR和GHBP mRNA显著多于对照组(P < 0.01)。(摘要截选至250字)