Ultrastructure of skin from Refsum disease with emphasis on epidermal lamellar bodies and stratum corneum barrier lipid organization.

Classic Refsum disease (RD) is a rare, autosomal recessively-inherited disorder of peroxisome metabolism due to a defect in the initial step in the alpha oxidation of phytanic acid (PA), a C16 saturated fatty acid with four methyl side groups, which accumulates in plasma and lipid enriched tissues (please see van den Brink and Wanders, Cell Mol Life Sci 63:1752-1765, 2006). It has been proposed that the disease complex in RD is in part due to the high affinity of phytanic acid for retinoid X receptors and peroxisome proliferator-activated receptors. Structurally, epidermal hyperplasia, increased numbers of cornified cell layers, presence of cells with lipid droplets in stratum basale and reduction of granular layer to a single layer have been reported by Blanchet-Bardon et al. (The ichthyoses, SP Medical & Scientific Books, New York, pp 65-69, 1978). However, lamellar body (LB) density and secretion were reportedly normal. We recently examined biopsies from four unrelated patients, using both OsO4 and RuO4 post-fixation to evaluate the barrier lipid structural organization. Although lamellar body density appeared normal, individual organelles often had distorted shape, or had non-lamellar domains interspersed with lamellar structures. Some of the organelles seemed to lack lamellar contents altogether, showing instead uniformly electron-dense contents. In addition, we also observed mitochondrial abnormalities in the nucleated epidermis. Stratum granulosum-stratum corneum junctions also showed co-existence of non-lamellar and lamellar domains, indicative of lipid phase separation. Also, partial detachment or complete absence of corneocyte lipid envelopes (CLE) was seen in the stratum corneum of all RD patients. In conclusion, abnormal LB contents, resulting in defective lamellar bilayers, as well as reduced CLEs, likely lead to impaired barrier function in RD.

Anaplastic large cell lymphoma in a reconstructed breast using a silicone implant: a UK case report.

We present case of Anaplastic Large Cell Lymphoma discovered as an incidental finding whilst revising an implant based breast reconstruction in a 55 year old woman, whom previously had undergone risk reduction mastectomies and immediate reconstruction. During the procedure a presumed seroma was present but this was macroscopically atypical giving a 'milky' coloured appearance with a pink tinge to it. The atypical fluid was sent for analysis and the diagnosis of ALCL confirmed. Treatment consisted of unilateral capsulectomy on the affected side and bilateral removal of implants with staging scans suggesting the disease being confined to the capsule. She remains in remission 12 months following the original procedure.

Barrier functions of human skin: a holistic view.

The fascinating topic of skin barrier continues to engage researchers from diverse disciplines both in academia and industry. Much of the information on the basic biology of barrier formation, its ontogeny as well as repair and homeostasis comes from studies on animal models. A smaller number of human studies have validated the usefulness of animal models, while highlighting some essential differences. We submit that the human skin barrier is unique in several ways, as much due to our adaptive ability as our control over the environment (macro and micro) that none of the other species have exerted. The human skin is not only exposed to the greatest variations of environment due to our phenomenal mobility but also to the largest number of xenobiotics, both chemical and microbial, resulting from human activity. In this overview, we attempt to evaluate the interdependent relation of skin barriers to environmental stressors hoping to raise interest in some of the lesser known or neglected aspects of human skin barriers as they relate to skin health and dysfunctions.

Water exchange and permeability properties of the skin in three species of amphibious sea snakes (Laticauda spp.).

Evolutionary transitions between different environmental media such as air and water pose special problems with respect to skin permeability because of the dramatic changes in the driving gradients and nature of water exchange processes. Also, during the transitional periods prior to complete adaptation to a new medium, the skin is exposed to two very different sets of environmental conditions. Here, we report new data for transepidermal evaporative water loss (TEWL) and cutaneous resistance to evaporative water loss (R(s)) of sea snakes that are transitional in the sense of being amphibious and semi-terrestrial. We investigated three species of sea kraits (Elapidae: Laticaudinae) that are common to Orchid Island (Lanyu), Taiwan. Generally, R(s) of all three species is lower than that characteristic of terrestrial/xeric species of snakes measured in other taxa. Within Laticauda, R(s) is significantly greater (TEWL lower) in the more terrestrial species and lowest (TEWL highest) in the more aquatic species. Previously reported losses of water from snakes kept in seawater exhibit a reversed trend, with lower rates of loss in the more aquatic species. These data suggest selection for adaptive traits with respect to increasing exposure to the marine environment. Thus, a countergradient of traits is reflected in decreased TEWL in aerial environments and decreased net water efflux in marine environments, acting simultaneously in the three species. The pattern for TEWL correlates with ultrastructural evidence for increased lipogenesis in the stratum corneum of the more terrestrial species. The skin surfaces of all three species are hydrophobic. Species differences in this property possibly explain the pattern for water efflux when these snakes are in seawater, which remains to be investigated.

Particle-mediated gene delivery and human skin: ultrastructural observations on stratum corneum barrier structures.

The particle-mediated delivery systems are becoming a clinically relevant tool in dermatology and immunology. We investigated the qualitative ultrastructural morphology of skin following pressure-driven delivery of gold particles to ex vivo human breast skin, at different pressures ranging from 350 to 1,000 psi. Pressures of 800 and 1,000 psi appear to be more effective, as indicated by distribution of particles in the viable epidermis and dermis. Particle bombardment of the skin with gold beads caused microwounds that spanned the stratum corneum (SC). The SC lipids did not reseal these wounds in the SC after 24 h in organ culture. The implications of particle-mediated delivery to permeability barrier functions of the SC are discussed.

Postnatal ecdysis establishes the permeability barrier in snake skin: new insights into barrier lipid structures.

A competent barrier to transepidermal water loss (TEWL) is essential for terrestrial life. In various vertebrates, epidermal water barriers composed of lipids prevent excessive TEWL, which varies inversely with habitat aridity. Little is known, however, about the mechanisms and regulation of permeability relative to natal transition from the 'aqueous' environments of gestation to the 'aerial' environments of terrestrial neonates. We investigated newly hatched California king snakes Lampropeltis getula to test the hypothesis that the first ecdysis is important for establishing the barrier to TEWL. We found that skin resistance to TEWL increases twofold following the first postnatal ecdysis, corresponding with a roughly twofold increase in thickness and deposition of lamellar lipids in the mesos layer, the site of the skin permeability barrier in snakes. In addition, novel observations on lipid inclusions within the alpha layer of epidermis suggest that this layer has functional similarities with avian epidermis. It appears that emergence of the integument from embryonic fluids, and its subsequent pan-body replacement following contact with air, are essential for completion of barrier competence in the newborn. These conditions provide a potentially useful model for investigations on the mechanism of barrier formation. We also found that hatchling snakes are transiently endothermic, with skin temperatures elevated by approximately 0.6 degrees C above ambient air temperature during the period of barrier formation. Behaviourally, hatchlings showed a higher tendency to seek humid microenvironments before the first ecdysis than after. The degree of water movement across the integument might explain the switch from reclusive to dispersive behaviours associated with postnatal ecdysis in snakes.

Basis of occlusive therapy in psoriasis: correcting defects in permeability barrier and calcium gradient.

BACKGROUND: Although occlusive dressings have great potential in the management of psoriasis vulgaris, the therapeutic mechanism is not completely understood. Occlusion artificially restores and corrects the defective barrier in psoriasis plaques. Additionally, occlusion is know to normalize the epidermal calcium gradients in hyperproliferative murine skin models. METHODS: To investigate the basis of the therapeutic effect of occlusion on psoriatic plaques, we investigated the ultrastructural morphology of intercorneocyte lipid layers, lamellar bodies, and calcium gradient in chronic plaque-type psoriasis after occlusion with a water vapor-impermeable membrane. The specimens were processed for electron microscopy using: (i) ruthenium tetroxide postfixation; and (ii) ion-capture cytochemistry for calcium localization. RESULTS: Occlusion for 7 days resulted in a nearly mature pattern of intercellular multilamellar structures, re-establishment of the near-normal epidermal calcium gradient, and disappearance of calcium precipitates from the stratum corneum interstices. CONCLUSIONS: The normalization of the permeability barrier and epidermal calcium gradient may play important roles in the therapeutic effects of occlusive dressings in chronic plaque-type psoriasis.

Transgenic oat plants via visual selection of cells expressing green fluorescent protein.

New selectable markers and selection systems are needed to increase the efficiency and flexibility of plant transformation. The objective of this research was to determine if the green fluorescent protein (gfp) gene could be utilized as a visual selectable marker for transformation of oat (Avena sativa L.). A modified gfp gene was delivered into oat cells by microprojectile bombardment. Cell clusters expressing gfp were visually identified using fluorescence microscopy and physically isolated at each subculture. Eleven independent transgenic cell lines were obtained, and fertile plants regenerated from all lines. Transgene integration and expression were confirmed in transgenic plants and progeny. Transgene expression segregated in a 3 : 1 ratio in progeny of the majority of the transgenic lines.

The secretory granular cell: the outermost granular cell as a specialized secretory cell.

The contents of epidermal lamellar bodies (LB) are delivered selectively to the intercellular spaces at the stratum granulosum (SG)-stratum corneum (SC) interface. We assessed the subcellular basis for LB secretion first by confocal microscopy, following labeling with Nile red or NBD-ceramide, which reveals a tubulo-reticular membrane system within the apical cytosol of the outermost SG cell layer under basal conditions, changing to a more peripheral staining pattern when secretion is stimulated. Ultrastructural study demonstrates that this network is composed of a widely disbursed trans-Golgi-like network (TGN), associated with arrays of contiguous LB, and deep invaginations of the SG-SC interface. Under basal conditions, limited fusion of apically directed LB leads to deep, interconnected invaginations of the apical plasma membrane, resulting in the formation of an extensive, honeycomb extension of the SG-SC interface. Still deeper invaginations and more extensive organelle fusion develop after the epidermis is acutely permeabilized by either acetone treatment, sonophoresis, or iontophoresis. Finally, nascent LB appear to bud off cisternae of the TGN, a process that appears to accelerate after barrier disruption. The deep invaginations of the SG-SC interface; the wide distribution of the TGN within the apical cytosol; the association of nascent LB with the TGN; and the rapid fusion of LB with these invaginations, deep within the cytosol, account for (i) the polarized secretion of LB from the apex of the outermost SG cell, and (ii) the rapid LB-secretory response to barrier perturbations. Finally, our results point to the outermost SG cell as a uniquely specialized secretory cell. We propose the term "secretory granulocyte" to encompass the specialized features of these cells.

Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier.

Alpha-hydroxy acids (AHA) such as glycolic acid have recently been used extensively in cosmetic and dermatological formulas. In low concentration (2-5%) glycolic acid is believed to facilitate progressive weakening of cohesion of the intercellular material of the stratum corneum (SC), resulting in uniform exfoliation of its outermost layers (the stratum disjunctum). Since thinning of the SC as well as changes of intercellular lipids could theoretically compromise the barrier functions of the skin, we investigated the mode of AHA action on the SC to determine whether enhanced desquamation compromises the barrier structures of the SC and changes transepidermal water loss (TEWL) values. Electron microscopy of the epidermis biopsied from the volar forearm of human volunteers after 3 weeks of treatment with a 4% glycolic acid formulation twice daily was employed to evaluate 1) epidermal morphology and thickness of the SC, (2) the lamellar body and SC lipid bilayer organization, and (3) desquamative events based on degradation of desmosomes. TEWL values and SC hydration were recorded prior to and at the end of the study. Electron microscopy revealed no ultrastructural changes in the nucleated layers of the epidermis. The lamellar body (LB) secretory system in the stratum granulosum (SG), and intercellular lipid lamellae in the SC in both vehicle- and glycolic acid-treated samples were comparable to normal human SC. Within the SC, enhanced desmosomal breakdown, promoting loss of cohesion and desquamation, was restricted to the stratum disjunctum while desmosomes of the stratum compactum were unaffected. Treated areas displayed histologically, a more compact appearing SC. TEWL values remained unchanged in glycolic acid- and vehicle-treated skin. Our findings indicate that the barrier structures of the SC are not disrupted by glycolic acid formulations at the concentration used. One of the mechanism of action of AHA on the SC seemed to be a "targeted" desmosomal (corneosomal) action without compromising the barrier structures of the skin.

Morphologic basis for a pore-pathway in mammalian stratum corneum.

Although prior morphologic studies have shown that both polar and nonpolar materials permeate across the stratum corneum (SC) via a paracellular route, the actual pathway through these heterogeneous domains is unknown. We applied hydrophilic and hydrophobic tracers in vivo to murine skin under basal conditions and/or after permeation enhancement with occlusion, vehicle enhancers, a lipid synthesis inhibitor, sonophoresis, and iontophoresis. Ruthenium tetroxide, ruthenium red plus osmium tetroxide, in situ precipitation with osmium vapor, and microwave postfixation methods were used to visualize penetration pathways. Tracers invariably localized to discrete lacunar domains embedded within the extracellular lamellar membrane system, regardless of their polarity or the enhancement method. Moreover, while the lacunar domains remained discontinuous under basal conditions, they appeared to gain structural continuity with permeation enhancement. These results indicate that extracellular lacunar domains comprise a pore pathway for penetration of polar and nonpolar molecules across the SC.

Ultrastructural organization of avian stratum corneum lipids as the basis for facultative cutaneous waterproofing.

The ultrastructure of naked neck epidermis from the ostrich (Struthio camelus) and ventral apterium from watered, and water-deprived, Zebra finches (Taeniopygia [Poephila] guttata castanotis) is presented. The form and distribution of the fully differentiated products of the lipid-enriched multigranular bodies are compared in biopsies post-fixed with osmium tetroxide or ruthenium tetroxide. The fine structure of ostrich epidermis suggests it is a relatively poor barrier to cutaneous water loss (CWL). The fine structure from watered, and 16-hr water-deprived Zebra finches, considered in conjunction with measurements of CWL, confirms previous reports of "facultative waterproofing," and emphasizes the rapidity of tissue response to dehydration. The seemingly counterintuitive facts that one xerophilic avian species, the ostrich, lacks a "good barrier" to CWL, whereas another, the Zebra finch, is capable of forming a good barrier, but does not always express this capability, are discussed. An explanation of these data in comparison to mammals centers on the dual roles of the integument of homeotherms in thermoregulation and conserving body water. It is concluded that birds, whose homeothermic control depends so much on CWL, cannot possess a permanent "good barrier," as such would compromise the heat loss mechanism. Facultative waterproofing (also documented in lizards) protects the organism against sudden reductions in water availability. In birds, and probably in snakes and lizards, facultative waterproofing involves qualitative changes in epidermal cell differentiation. Possible control mechanisms are discussed.

Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations.

Permeability barrier requirements regulate epidermal beta-glucocerebrosidase.

The intercellular spaces of the outermost layers of the epidermis (stratum corneum, SC) of terrestrial mammals contain a mixture of lipids, enriched in ceramides that are critical for the epidermal permeability barrier. Whereas glucosylceramides (GlcCer) are synthesized in abundance in the epidermis, they disappear coincident with an increase of ceramides (Cer) in the SC. Hence, hydrolysis of GlcCer to Cer by beta-glucocerebrosidase (GlcCer'ase), may be required for permeability barrier homeostasis. We determined first whether modulations in epidermal GlcCer'ase activity and mRNA levels occur in response to barrier disruption; and second, how GlcCer'ase inhibitors influence barrier function and SC membrane ultrastructure. Barrier disruption significantly increased epidermal GlcCer'ase mRNA levels, with a 2.8-fold increase over untreated control levels at 8 h (P < 0.01). GlcCer'ase activity was increased in whole epidermis (34%; P < 0.02) 24 h after barrier disruption. Localization of GlcCer'ase activity showed an increase (33%; P < 0.05) in the outer epidermis (SC and stratum granulosum), without a change in lower epidermal activity (stratum spinosum and stratum basale). Furthermore, a single topical application of the GlcCer'ase inhibitor, bromoconduritol-B-epoxide (BrCBE), inhibited enzyme activity (98%) and significantly delayed permeability barrier recovery after acetone treatment. In addition, BrCBE treatment disrupted SC intercellular lamellar bilayers, without evidence of cellular toxicity. These results indicate that epidermal processing of GlcCer to Cer by GlcCer'ase is required for barrier homeostasis, and that this important enzymatic step is regulated by barrier requirements.

Selective obliteration of the epidermal calcium gradient leads to enhanced lamellar body secretion.

The epidermal permeability barrier is formed by lipids delivered to the intercellular spaces through the secretion of lamellar bodies. Prior studies have shown that the rate of lamellar body secretion appears to be regulated by the extracellular calcium content of the upper epidermis, which is altered following permeability barrier disruption. To determine directly whether changes in extracellular calcium content in the upper epidermis versus disruption of the barrier regulate lamellar body secretion, we experimentally manipulated the Ca++ content of the upper epidermis by sonophoresis of aqueous solutions containing physiologic Ca++ (and K+) versus ion-free solutions across hairless mouse stratum corneum. Sonophoresis at 15 MHz did not alter barrier function, but in the absence of Ca++ the extracellular calcium content of the outer epidermis, as revealed by ion capture cytochemistry, was displaced downward toward the basal layer and dermis. In contrast, following sonophoresis of Ca(++)-containing solutions, the extracellular Ca++ gradient became obscured by excess Ca++ in the cytosol at all levels of the epidermis. These changes in the extracellular calcium content lead, in turn, to accelerated lamellar body secretion (with low Ca++), or basal rates of lamellar body secretion (with normal Ca++). These results demonstrate that the epidermal extracellular calcium content in the upper epidermis can be manipulated by sonophoresis without prior barrier disruption, and that changes in the Ca++ gradient induce lamellar body secretion, independent of barrier disruption.

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

Hydrolysis of glucosylceramide by beta-glucocerebrosidase results in ceramide, a critical component of the intercellular lamellae that mediate the epidermal permeability barrier. A subset of type 2 Gaucher patients displays ichthyosiform skin abnormalities, as do transgenic Gaucher mice homozygous for a null allele. To investigate the relationship between glucocerebrosidase deficiency and epidermal permeability barrier function, we compared the stratum corneum (SC) ultrastructure, lipid content, and barrier function of Gaucher mice to carrier and normal mice, and to hairless mice treated topically with bromoconduritol B epoxide (BrCBE), an irreversible inhibitor of glucocerebrosidase. Both Gaucher mice and BrCBE-treated mice revealed abnormal, incompletely processed, lamellar body-derived sheets throughout the SC interstices, while transgenic carrier mice displayed normal bilayers. The SC of a severely affected type 2 Gaucher's disease infant revealed similarly abnormal ultrastructure. Furthermore, the Gaucher mice demonstrated markedly elevated transepidermal water loss (4.2 +/- 0.6 vs < 0.10 g/m2 per h). The electron-dense tracer, colloidal lanthanum, percolated between the incompletely processed lamellar body-derived sheets in the SC interstices of Gaucher mice only, demonstrating altered permeability barrier function. Gaucher and BrCBE-treated mice showed < 1% and < 5% of normal epidermal glucocerebrosidase activity, respectively, and the epidermis/SC of Gaucher mice demonstrated elevated glucosylceramide (5- to 10-fold), with diminished ceramide content. Thus, the skin changes observed in Gaucher mice and infants may result from the formation of incompetent intercellular lamellar bilayers due to a decreased hydrolysis of glucosylceramide to ceramide. Glucocerebrosidase therefore appears necessary for the generation of membranes of sufficient functional competence for epidermal barrier function.

Integrity of the permeability barrier is crucial for maintenance of the epidermal calcium gradient.

Prior studies have demonstrated a Ca2+ gradient within the epidermis, with the highest concentration in the outer nucleated layers, disappearance of the Ca2+ gradient when the permeability barrier is acutely disrupted, and reappearance of the Ca2+ gradient in parallel with barrier repair, and disruption of the gradient in psoriasis. These observations suggest that integrity of the permeability barrier may maintain the epidermal Ca2+ gradient. To determine further whether a functional barrier is crucial for maintaining the Ca2+ gradient, we examined Ca2+ distribution by ion-capture cytochemistry in essential-fatty-acid-deficient (EFAD) and topical-lovastatin-treated mice, which display a chronic barrier abnormality. In both models, loss of the Ca2+ gradient occurred due to increased cytosolic Ca2+ in the lower epidermis, which normally displays a paucity of Ca2+. Moreover, artificial barrier restoration for 48 h with a water vapour-impermeable wrap normalized the Ca2+ distribution pattern. Acute barrier disruption also leads to the loss of the Ca2+ gradient, but in contrast with the chronic models, loss of the gradient was due to decreased Ca2+ in the upper epidermis. Occlusion with a vapour-impermeable wrap blocked restoration of the Ca2+ gradient after acute barrier disruption. These results demonstrate that chronic barrier disruption increases Ca2+ in the epidermis, and blockade of water flux normalizes Ca2+ distribution, whereas acute barrier disruption leads to loss of Ca2+, and blockade of water flux prevents the return of Ca2+. We conclude: (i) that the epidermal Ca2+ reservoir is derived from the movement of fluids and Ca2+ across the basement membrane, and (ii) that the integrity of the permeability barrier maintains the epidermal Ca2+ gradient.

High-frequency sonophoresis: permeation pathways and structural basis for enhanced permeability.

The mechanism of stratum corneum (SC) permeabilization by ultrasound (sonophoresis) is unknown. We studied here permeation pathways, and SC intercellular structural organization following applications of high-frequency sonophoresis to hairless mouse skin. Ruthenium tetroxide post-fixation and tracer solutions of LaNO3 and FITC-dextrans were employed to examine SC lamellar bilayers, lamellar body morphology and subcellular permeation pathways. Sonophoresis disrupted the compact organization of SC bilayers and LB-derived contents at the stratum granulosum (SG)-SC interface, leading to domain separation between 0 and 20 h, reverting by 48 h. Post-sonophoresis, tracers traversed the SC via lacunae within the lamellar bilayers, and via lamellae in sites that displayed domain separation. These studies provide insights about the penetration pathways, permeabilizing mechanisms, and kinetics of sonophoresis on the epidermis.

Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat.

The cutaneous permeability barrier to systemic water loss is mediated by hydrophobic lipids forming membrane bilayers within the intercellular domains of the stratum corneum (SC). The barrier emerges during day 20 of gestation in the fetal rat and is correlated with increasing SC thickness and increasing SC lipid content, the appearance of well-formed lamellar bodies in the epidermis, and the presence of lamellar unit structures throughout the SC. Because glucocorticoids accelerate lung lamellar body and surfactant maturation in man and experimental animals, these studies were undertaken to determine whether maternal glucocorticoid treatment accelerates maturation of the epidermal lamellar body secretory system. Maternal rats were injected with betamethasone or saline (control) on days 16-18, and pups were delivered prematurely on day 19. Whereas control pups exhibited immature barriers to transepidermal water loss (8.16 +/- 0.52 mg/cm2 per h), glucocorticoid-treated pups exhibited competent barriers (0.74 +/- 0.14 mg/cm2 per h; P < 0.001). Glucocorticoid treatment also: (a) accelerated maturation of lamellar body and SC membrane ultrastructure; (b) increased SC total lipid content twofold; and (c) increased cholesterol and polar ceramide content three- to sixfold. Thus, glucocorticoids accelerate the functional, morphological, and lipid biochemical maturation of the permeability barrier in the fetal rat.