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Hypothyroidism delays fetal stratum corneum development in mice
K Hanley1, U P Devaskar, S J Hicks
1Department of Medicine and Dermatology, University of California, San Francisco 94121, USA.
Insights
Thyroid hormone plays a key role in fetal skin barrier development. While essential for normal maturation, it is not absolutely required for the stratum corneum (SC) to fully develop postnatally.
Area of Science:
- Developmental biology
- Skin physiology
- Endocrinology
Background:
- The epidermal permeability barrier, crucial for terrestrial life, resides in the stratum corneum (SC).
- SC immaturity is a major cause of complications in premature infants.
- Thyroid hormone is known to accelerate SC development at high concentrations.
Purpose of the Study:
- To investigate the physiological role of thyroid hormone in fetal SC development.
- To examine SC development in genetically hypothyroid (Hyt/Hyt) mice.
- To determine the interaction between glucocorticoids and thyroid hormone in SC maturation.
Main Methods:
- Comparison of SC development in control and Hyt/Hyt mice at different gestational ages (18 and 19 days).
- Assessment of epidermal and SC structure postnatally.
- Evaluation of glucocorticoid effects on SC development in euthyroid and hypothyroid states.
Main Results:
- SC development was delayed in Hyt/Hyt mice compared to controls during late gestation.
- Postnatal development showed no differences, with SC fully mature in both groups within one day after birth.
- Glucocorticoids accelerated SC development in euthyroid mice but not in Hyt/Hyt mice, suggesting a dependence on thyroid hormone or a euthyroid state.
Conclusions:
- Thyroid hormone has a physiological role in normal intrauterine SC development.
- Thyroid hormone is not absolutely essential for ultimate SC maturation.
- Glucocorticoid-induced SC maturation appears to require a euthyroid state, potentially acting through thyroid hormone.
Abstract:
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.