title: Ontogeny of the epidermal permeability barrier.
abstract: A competent permeability barrier must be present by the end of gestation to allow for life in a terrestrial environment. Indeed, early preterm infants display serious complications of skin immaturity. Yet, regardless of their degree of prematurity, all infants quickly develop a competent barrier. To learn more about the mechanisms and regulation of barrier ontogeny, we have utilized late-gestation fetal rodents. In 19-21 d fetal rats, we showed that barrier competence is accompanied by both enhanced epidermal development and formation of extracellular lamellar membranes in the stratum corneum. The identical sequence and time-course occurs when fetal rat skin is cultured in a serum-free medium. Glucocorticoids, thyroid hormone (T3), and estrogen accelerate, while androgens delay barrier formation both in utero and in the in vitro system, explaining the poorer outcome of premature males versus females. But neither T3 nor glucocorticoids are absolutely required for barrier development. Lifting fetal skin cultures to an air-medium interface also accelerates barrier formation, explaining the rapid emergence of barrier competence in very premature infants. PPARalpha and FXR activators, which, like T3, heterodimerize with the nuclear receptor, RXR, also accelerate barrier development in vitro. Finally, not only the nuclear receptor family, but also Ca++ could regulate key events late in barrier development.
authors.affiliation: Dermatology Service, Veterans Affairs Medical Center, San Francisco, California 94121, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Williams
authors.forename: K
authors.initials: K
authors.lastname: Hanley
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D004817:Epidermis / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000196:embryology; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000502:physiology; D010539:Permeability; D051381:Rats / Q000196:embryology
chemical_list: D005938:Glucocorticoids; D006728:Hormones; D002118:Calcium