Hanley K, Devaskar U P, Hicks S J, Jiang Y, Crumrine D, Elias P M, Williams M L, Feingold K R
Department of Medicine and Dermatology, University of California, San Francisco 94121, USA.
Pediatr Res. 1997 Nov;42(5):610-4. doi: 10.1203/00006450-199711000-00010.
The epidermal permeability barrier, required for terrestrial life, is localized to lipid-enriched lamellar membranes in the extracellular spaces of the stratum corneum (SC). Immaturity of the SC is a significant contributor to morbidity and mortality in premature infants. Previous studies have shown that supraphysiologic concentrations of thyroid hormone accelerate epidermis/SC ontogenesis. Here we studied SC development in Hyt/Hyt mice who are genetically hypothyroid due to a mutation in the TSH receptor. In control mice on d 18 of gestation (term 19.5 d), only focal areas displayed a mature SC membrane pattern. By 19 d of gestation there was a mature multilayered SC with lamellar unit structures filling the extracellular spaces similar to that seen in mature mice. In Hyt/Hyt mice SC development was delayed at both 18 and 19 d of gestation. In both strains of mice, within the first day after birth there were no differences in epidermal or SC appearance, and the SC was fully mature. These findings indicate that thyroid hormone plays a physiologic role during normal intrauterine development of the SC. However, normal SC maturation ultimately occurs, indicating that thyroid hormone is not absolutely essential. Previous studies have shown that glucocorticoids accelerate SC development in euthyroid rats, and in the present study we demonstrate that glucocorticoids also accelerate SC ontogenesis in euthyroid mice. In contrast, in Hyt/Hyt mice glucocorticoids did not accelerate or normalize SC development, indicating that the glucocorticoid effect on SC maturation requires a euthyroid state or that glucocorticoids act via thyroid hormone. These studies demonstrate that thyroid hormone status is an important regulator of fetal SC development.
陆地生物生存所必需的表皮渗透屏障定位于角质层（SC）细胞外空间富含脂质的板层膜中。SC发育不成熟是早产儿发病和死亡的重要原因。先前的研究表明，超生理浓度的甲状腺激素可加速表皮/SC的发生。在此，我们研究了因促甲状腺激素受体突变而遗传性甲状腺功能减退的Hyt/Hyt小鼠的SC发育情况。在妊娠第18天（足月为19.5天）的对照小鼠中，只有局部区域呈现成熟的SC膜模式。到妊娠第19天，出现了成熟的多层SC，其板层单位结构填充细胞外空间，类似于成熟小鼠所见。在Hyt/Hyt小鼠中，SC发育在妊娠第18天和第19天均延迟。在这两种品系的小鼠中，出生后第一天表皮或SC外观无差异，且SC已完全成熟。这些发现表明，甲状腺激素在SC正常的子宫内发育过程中发挥生理作用。然而，SC最终会正常成熟，这表明甲状腺激素并非绝对必需。先前的研究表明，糖皮质激素可加速甲状腺功能正常大鼠的SC发育，在本研究中我们证明，糖皮质激素也可加速甲状腺功能正常小鼠的SC发生。相反，在Hyt/Hyt小鼠中，糖皮质激素并未加速或使SC发育正常化，这表明糖皮质激素对SC成熟的作用需要甲状腺功能正常状态，或者糖皮质激素通过甲状腺激素发挥作用。这些研究表明，甲状腺激素状态是胎儿SC发育的重要调节因子。
