HYPOTHYROIDISM DELAYS FETAL STRATUM-CORNEUM DEVELOPMENT IN MICE

The epidermal permeability barrier, required for terrestrial life, is localized to lipid-enriched lamellar membranes in the extracellular sp aces of the stratum corneum (SC). Immaturity of the SC is a significan t contributor to morbidity and mortality in premature infants. Previou s studies have shown that supraphysiologic concentrations of thyroid h ormone accelerate epidermis/SC ontogenesis. Here we studied SC develop ment 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 o f gestation there was a mature multilayered SC with lamellar unit stru ctures 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 birt h 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. Ho wever, 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 t he present study we demonstrate that glucocorticoids also accelerate S C ontogenesis in euthyroid, mice. In contrast, in Hyt/Hyt mice glucoco rticoids did not accelerate or normalize SC development, indicating th at the glucocorticoid effect on SC maturation requires a euthyroid sta te or that glucocorticoids act via thyroid hormone. These studies demo nstrate that thyroid hormone status is an important regulator of fetal SC development.