围生期甲状腺功能低下对仔鼠大脑皮质及海马AR mRNA影响的研究

Expression of androgen receptor gene in cerebral cortex and hippocampus of rats with perinatal hypothyroidism

目的:研究围生期甲状腺功能低下(甲低)对仔鼠大脑皮质及海马雄激素受体mRNA(ARmRNA)表达的影响。方法:对雌大鼠从孕15d起每日以丙基硫氧嘧啶(PTU)溶液灌胃(50mg/d)至断奶,造成大鼠围生期甲低模型,部分甲低仔鼠每日腹腔注射左旋甲状腺素(L-T4)2μg/100g体重。收集出生后1、5、10、15、20d的正常、甲低及T4-替代仔鼠的大脑皮质及海马组织,用竞争性RT-PCR法测定ARmRNA水平。结果:正常组仔鼠生后ARmR-NA水平随日龄增加而增高,海马高于大脑皮质,雄性组高于雌性组。与同日龄正常对照组相比,甲低组大脑皮质及海马ARmRNA水平明显降低。T4-替代组ARmRNA水平增加,但在10、20日龄的雄性组和15、20日龄的雌性组海马的表达仍未达正常对照组水平,大脑皮质各组与正常组已无显著性差异。结论:围生期甲状腺功能低下会引起发育期大鼠大脑皮质和海马的ARmRNA表达下降,及时替代治疗能恢复大脑皮质ARmRNA的正常表达,但海马的ARmRNA表达则未能达到正常水平。

Objective： To investigate the effects of perinatal thyroid hormone deficiency on the expression of androgen receptor （AR） mRNA in cerebral cortex and hippocampus of rats. Methods： Perinatal hypothyroidism was induced by the administration of propylthiouracil （PTU） solution to the dams by gavage （50 mg/d） beginning at embryonic d15 throughout the lactational period. In the T4 injected group hypothyroid rats were injected intraperitoneally with levothroxine （L-T4） 2 μg/100 g BW daily,starting from the day of birth. Cerebral cortex and hippocampus specimen were collected from controls ,hypothyroid and T4-injected hypothyroid rats on postnatal d1, 5,10,15 and 20. Quantification of ARmRNA in cerebral cortex and hippocampus was performed with competitive RT-PCR using internal and external standardization. Results： Age-related increasing ARmRNA levels were observed in neonatal rats,and those in male animals were significantly higher. AR expression was higher in the hippocampus than in the cerebral cortex. ARmRNA levels in the hypothyroid pups were lower than those in agematched controls. The mRNA levels in the T4-injected hypothyroid pups were significantly higher compared with the age-matched hypothyroid pups,but in hippocampus ARmRNA expression did not reach normal levels in male rats at d l0 and d20,in female at d15 and d20. Conclusion： The expression of ARmRNA decreases in brain of rats with perinatal hypothyroidism. Treatment with thyroid hormone can recover ARmRNA expression in cerebral cortex, but not in hippocampus.