Ansari M A, Demello D E, Polk D H, Devaskar U P
Department of Pediatrics, St. Louis University School of Medicine and the Pediatric Research Institute, Missouri 63104, USA.
Pediatr Res. 1997 Nov;42(5):709-14. doi: 10.1203/00006450-199711000-00025.
Maternal administration of TSH-releasing hormone (TRH) in the euthyroid mouse accelerates fetal lung ultrastructural maturation. However, the mechanism(s) of TRH in fetal lung development remains unclear; it could be due to its neuroendocrine and/or neurotransmitter effects. Although the neuroendocrine effect of TRH is mediated via stimulation of the fetal pituitary-thyroid axis, the neurotransmitter effect is mediated via stimulation of fetal autonomic nervous system activity. In the hyt/hyt mouse there is a point mutation in the beta subunit of the TSH receptor in the thyroid gland of the Balb-c mouse. In these mice TSH does not bind to its receptors, leading ultimately to the development of primary hypothyroidism, which is transmitted as an autosomal recessive trait. A maturational delay in the lung ultrastructure of the hyt/hyt mouse fetus has been observed. This investigation was undertaken to study the effect of maternal TRH treatment on lung ultrastructural maturation in the hyt/hyt mouse fetus. If the effect of TRH is mediated via stimulation of fetal pituitary-thyroid axis, TRH treatment should not enhance lung maturity in the hyt/hyt fetus and vice versa. Adult hyt/hyt mice made euthyroid by triiodothyronine supplementation were mated to carry hyt/hyt pups. Saline or TRH (0.4 or 0.6 mg/kg/dose) was administered to the mother (i.p.) on d 16 and 17 (b.i.d.) and on d 18 of pregnancy 1 h before killing (term, approximately 20 d). The fetal lung electron micrographs were subjected to ultrastructural morphometric analysis of the number of lamellar bodies and glycogen/nuclear ratio in type II cells, and the alveolar/parenchymal ratio by Chalkley point counting with an interactive computerized image analyzer (Optimas, Bioscan). Fetal lungs exposed to the lower dose of TRH (n = 7) showed no significant difference in their ultrastructural maturation when compared with saline-treated controls (n = 5). However, fetal lungs exposed to a higher dose of TRH (n = 6) showed increased numbers of lamellar bodies per type II cell, an increase in the alveolar/parenchymal ratio, larger air spaces, thinner alveolar septa, presence of tubular myelin, and increased numbers of air-blood barriers. We conclude that the effect of TRH in accelerating fetal mouse lung maturation is at least in part mediated via stimulation of extra thyroidal pathways.
在甲状腺功能正常的小鼠中，母体给予促甲状腺激素释放激素（TRH）可加速胎儿肺超微结构成熟。然而，TRH在胎儿肺发育中的作用机制仍不清楚；这可能是由于其神经内分泌和/或神经递质作用。虽然TRH的神经内分泌作用是通过刺激胎儿垂体-甲状腺轴介导的，但其神经递质作用是通过刺激胎儿自主神经系统活动介导的。在hyt/hyt小鼠中，Balb-c小鼠甲状腺中促甲状腺激素（TSH）受体的β亚基存在点突变。在这些小鼠中，TSH不与其受体结合，最终导致原发性甲状腺功能减退的发生，该疾病作为常染色体隐性性状遗传。已观察到hyt/hyt小鼠胎儿的肺超微结构成熟延迟。本研究旨在探讨母体TRH治疗对hyt/hyt小鼠胎儿肺超微结构成熟的影响。如果TRH的作用是通过刺激胎儿垂体-甲状腺轴介导的，那么TRH治疗不应增强hyt/hyt胎儿的肺成熟度，反之亦然。通过补充三碘甲状腺原氨酸使成年hyt/hyt小鼠甲状腺功能正常后进行交配，以孕育hyt/hyt幼崽。在妊娠第16天和第17天（每日两次）以及妊娠第18天处死前1小时（足月约20天），给母鼠腹腔注射生理盐水或TRH（0.4或0.6mg/kg/剂量）。对胎儿肺电子显微照片进行超微结构形态计量分析，计算II型细胞中板层小体的数量和糖原/核比率，并使用交互式计算机图像分析仪（Optimas，Bioscan）通过Chalkley点计数法计算肺泡/实质比率。与生理盐水处理的对照组（n = 5）相比，接受较低剂量TRH（n = 7）处理的胎儿肺在超微结构成熟方面无显著差异。然而，接受较高剂量TRH（n = 6）处理的胎儿肺中，每个II型细胞的板层小体数量增加、肺泡/实质比率增加、气腔增大、肺泡间隔变薄、出现管状髓磷脂以及气血屏障数量增加。我们得出结论，TRH加速胎儿小鼠肺成熟的作用至少部分是通过刺激甲状腺外途径介导的。
