RESUMEN
In this study, we present a detailed phenotype description and genetic elucidation of the first case of X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund. This condition is characterized by partial congenital hypotrichosis, missing and malformed teeth and a lack of eccrine sweat glands. Clinical signs including dental radiographs and histopathological findings were consistent with ectodermal dysplasia. Pedigree analysis supported an X-recessive mode of inheritance. Whole-genome sequencing of one affected puppy and his dam identified a 1-basepair deletion within the ectodysplasin-A (EDA) gene (CM000039.3:g.54509504delT, c.458delT). Sanger sequencing of further family members confirmed the EDA:c.458delT-variant. Validation in all available family members, 37 unrelated shorthaired standard Dachshunds, 128 further Dachshunds from all other coat and size varieties and samples from 34 dog breeds revealed the EDA:c.458delT-variant to be private for this family. Two heterozygous females showed very mild congenital hypotrichosis but normal dentition. Since the dam is demonstrably the only heterozygous animal in the ancestry of the affected animals, we assume that the EDA:c.458delT-variant arose in the germline of the granddam or in an early embryonic stage of the dam. In conclusion, we detected a very recent de-novo EDA mutation causing X-linked hypohidrotic ectodermal dysplasia in the shorthaired standard Dachshund.
Asunto(s)
Enfermedades de los Perros/genética , Displasia Ectodermal Anhidrótica Tipo 1/genética , Ectodisplasinas/genética , Secuenciación Completa del Genoma , Animales , Enfermedades de los Perros/fisiopatología , Perros , Displasia Ectodermal Anhidrótica Tipo 1/patología , Humanos , Linaje , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/patologíaRESUMEN
It is a significant challenge to regenerate full-thickness skin defects with sweat glands. Various skin substitutes have been developed to resolve this issue with minimal success. In this study, to yield a novel construct for in situ regeneration of sweat glands, the collagen-chitosan porous scaffold was combined with Lipofectamine 2000/pDNA-EGF complexes to obtain the gene-activated scaffold (GAS), which was then seeded with bone marrow-derived mesenchymal stem cells (BM-MSCs). The porous scaffold functionalized as a reservoir for the incorporated gene complexes which were released in a sustained manner. The seeded BM-MSCs were transfected in situ by the released complexes and specially differentiated into sweat gland cells in vitro under the induction of the expressed epidermal growth factor (EGF). Application in vivo of the GAS/BM-MSCs constructs on the full-thickness skin defects of SD rats confirmed that GAS/BM-MSCs could accelerate the wound healing process and induce the in situ regeneration of the full-thickness skin with sweat gland-like structures. Analyzed by immunohistochemical staining, RT-qPCR and Western-blotting, the levels of the major sweat gland markers such as carcino-embryonic antigen (CEA), cytokeratin 8 (CK8) and cytokeratin 14 (CK14) were all up-regulated, indicating that GAS/BM-MSCs can facilitate the regeneration of sweat glands-like structure in vivo.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Regeneración/fisiología , Glándulas Sudoríparas/citología , Glándulas Sudoríparas/crecimiento & desarrollo , Animales , Células de la Médula Ósea/citología , Antígeno Carcinoembrionario/metabolismo , Diferenciación Celular , Supervivencia Celular , Células Cultivadas , ADN/farmacología , Factor de Crecimiento Epidérmico/farmacología , Queratina-14/metabolismo , Queratina-8/metabolismo , Lípidos , Ratas , Ratas Sprague-Dawley , Piel Artificial , Andamios del Tejido , Cicatrización de Heridas/fisiologíaAsunto(s)
Displasia Ectodérmica/genética , Proteínas I-kappa B/metabolismo , Infecciones/genética , Glándulas Sudoríparas/patología , Linfocitos T/inmunología , Displasia Ectodérmica/complicaciones , Displasia Ectodérmica/diagnóstico , Femenino , Predisposición Genética a la Enfermedad , Humanos , Proteínas I-kappa B/genética , Pruebas Inmunológicas/métodos , Lactante , Recién Nacido , Infecciones/diagnóstico , Infecciones/etiología , Activación de Linfocitos/genética , Mutación Missense/genética , Inhibidor NF-kappaB alfa , FN-kappa B/metabolismo , Organogénesis/genética , Polimorfismo Genético , Transducción de Señal/genética , Glándulas Sudoríparas/embriología , Glándulas Sudoríparas/crecimiento & desarrolloRESUMEN
Os hidrocistomas écrinos são lesões raras, císticas e benignas, que resultam em deformidades nas regiões palpebrais bilateralmente. Vários tratamentos são citados na literatura, porém nenhum deles é considerado padrão de referência. Deve-se somar as impressões obtidas à avaliação clínica e aos recursos disponíveis. Paciente de 73 anos, feminino, apresentando tumorações em regiões palpebrais bilaterais, de crescimento lento, com obstrução parcial do campo de visão e ectrópio. Foi submetida a dois procedimentos cirúrgicos para ressecção, em 2007 e em 2008. Apresentou melhora significativa do contorno palpebral bilateral, com boa simetria entre as regiões. O exame histopatológico concluiu: hidrocistoma écrino. O tratamento cirúrgico para a polipose palpebral bilateral relacionada ao hidrocistoma écrino mostrou-se uma modalidade que pode apresentar bons resultados estéticos e funcionais, sendo reprodutível, e sem causar maiores morbidades pós-operatórias ao paciente.
Eccrine hidrocystomas are rare lesions, cysts, or benign tumors, which lead to bilateral deformities in the eyelid areas. Several treatments are described in the literature. However, none of them has been established as the gold standard. Hence, it becomes necessary to consider the contribution of different opinions and available resources to clinical evaluation. A 73-year-old female patient presented with slow-growing tumors on both eyelids, which consequently led to partial visual field obstruction and ectropion. She underwent 2 surgical resections, one in 2007 and the other in 2008. As a result, she showed significant improvement of the bilateral eyelid contours and satisfactory symmetry between the areas. Histopathological diagnosis indicated eccrine hidrocystoma. The surgical treatment of bilateral eyelid polyposis associated with eccrine hidrocystoma proved to be a reproducible procedure that may ensure satisfactory aesthetic and functional results, without causing major postoperative morbidities to the patient.
Asunto(s)
Humanos , Femenino , Anciano , Cirugía Plástica , Neoplasias de las Glándulas Sudoríparas , Neoplasias de las Glándulas Sudoríparas/cirugía , Glándulas Sudoríparas , Hidrocistoma , Neoplasias de los Párpados , Párpados , Cara , Cirugía Plástica/métodos , Glándulas Sudoríparas/anomalías , Glándulas Sudoríparas/cirugía , Glándulas Sudoríparas/crecimiento & desarrollo , Hidrocistoma/cirugía , Neoplasias de los Párpados/cirugía , Párpados/cirugía , Cara/cirugíaRESUMEN
The morphogenesis of mammalian cutaneous glands is considered based on the analysis of the literature and our own original data with the focus on the issues of gland polymorphism and specific features in postnatal development (from the case study of circumanal hepatoid glands of newborn domestic dogs), including the features reflecting the evolutionary relationships of various types of cutaneous glands. The hepatoid glands are a component of the glandular complex ofthe hair follicle, which also includes sebaceous and sweat glands; have a specific structure; and produce protein secretion by a merocrine pathway. Characteristic of these glands are wide polymorphism, sex- and age-related differences in the degree of development, occurrence in only a few phylogenetically related mammalian taxa (even-toed ungulates and carnivores); and a signaling type of their secretion. The data support the "generative concept," relying on the idea of a separate and independent origination of diverse derivatives of the external integuments.
Asunto(s)
Evolución Biológica , Morfogénesis/fisiología , Glándulas Sebáceas/crecimiento & desarrollo , Piel/crecimiento & desarrollo , Glándulas Sudoríparas/crecimiento & desarrollo , Factores de Edad , Animales , Animales Recién Nacidos , Perros , Folículo Piloso/anatomía & histología , Folículo Piloso/crecimiento & desarrollo , Filogenia , Glándulas Sebáceas/anatomía & histología , Glándulas Sebáceas/metabolismo , Factores Sexuales , Piel/anatomía & histología , Glándulas Sudoríparas/anatomía & histología , Glándulas Sudoríparas/metabolismoRESUMEN
Sweat glands play a fundamental role in thermal regulation in man, but the molecular mechanism of their development remains unknown. To initiate analyses, we compared the model of Eda mutant Tabby mice, in which sweat glands were not formed, with wild-type (WT) mice. We inferred developmental stages and critical genes based on observations at seven time points spanning embryonic, postnatal and adult life. In WT footpads, sweat gland germs were detected at E17.5. The coiling of secretory portions started at postnatal day 1 (P1), and sweat gland formation was essentially completed by P5. Consistent with a controlled morphological progression, expression profiling revealed stage-specific gene expression changes. Similar to the development of hair follicles-the other major skin appendage controlled by EDA-sweat gland induction and initial progression were accompanied by Eda-dependent up-regulation of the Shh pathway. During the further development of sweat gland secretory portions, Foxa1 and Foxi1, not at all expressed in hair follicles, were progressively up-regulated in WT but not in Tabby footpads. Upon completion of WT development, Shh declined to Tabby levels, but Fox family genes remained at elevated levels in mature sweat glands. The results provide a framework for the further analysis of phased down-stream regulation of gene action, possibly by a signaling cascade, in response to Eda.
Asunto(s)
Displasia Ectodérmica/metabolismo , Factores de Transcripción Forkhead/metabolismo , Proteínas Hedgehog/metabolismo , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/metabolismo , Animales , Displasia Ectodérmica/embriología , Displasia Ectodérmica/genética , Femenino , Factores de Transcripción Forkhead/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog/genética , Factor Nuclear 3-alfa del Hepatocito/genética , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Familia de Multigenes , Glándulas Sudoríparas/embriologíaRESUMEN
The evolution of aquaporin-5 (AQP5) expression during postnatal development has not been defined in the sweat gland. Previous studies have suggested that AQP isoforms in several peripheral targets are regulated by a neural mechanism. We have examined, in rat sweat glands, the expression of AQP5 during postnatal development and the effects of denervation on AQP5 expression. Both AQP5 mRNA and protein begin to be expressed at postnatal day 10, before sweat-secretory responsiveness first appears; this expression coincides with the occurrence of vasoactive intestinal peptide (VIP) immunoreactivity. Early noradrenergic and later cholinergic interaction between sweat glands and their innervation are disrupted by neonatal chemical sympathectomy or postnatal severance of the sciatic nerve. Examination of such denervated developing rats has shown that secretory responsiveness fails to arise later in the adults, and AQP5 immunostaining increases in the denervated glands, whereas gland morphogenesis and the occurrence of AQP5 expression proceed normally. Immunobloting has revealed an increase of AQP5 abundance after the denervated mature glands lose their secretory ability. These findings suggest that AQP5 protein is necessary for sweat secretion, and that the expression of AQP5 in rat sweat glands is independent of sympathetic innervation. Our data also indicate that factor(s) regulating the normal morphological development of sweat gland might be responsible for controlling AQP5 expression.
Asunto(s)
Acuaporina 5/biosíntesis , Regulación de la Expresión Génica , Glándulas Sudoríparas/inervación , Glándulas Sudoríparas/metabolismo , Animales , Animales Recién Nacidos , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Nervio Ciático/metabolismo , Nervio Ciático/patología , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/patología , Simpatectomía QuímicaRESUMEN
OBJECTIVE: To investigate the expression of ectodysplasin (EDA) gene signaling and its relationship with the development and regeneration of sweat glands. METHODS: The articles concerned in the latest years were extensively reviewed. RESULTS: EDA gene is an important signaling pathway associated with the developmental procedure of sweat glands in early fetal stage. Abnormality or depletion of function in sweat glands partially owed to the defect of EDA gene. CONCLUSION: EDA signaling has its biological significance in inducing development and morphogenesis of sweat glands and in maintaining physiological function of skin. It could be a new approach to repair or regenerate the sweat glands for clinical therapy by regulating the expression of EDA gene.
Asunto(s)
Ectodisplasinas/genética , Transducción de Señal/genética , Glándulas Sudoríparas/fisiología , Ectodisplasinas/fisiología , Humanos , Glándulas Sudoríparas/crecimiento & desarrolloRESUMEN
Mutations in the EDA gene cause anhidrotic/hypohidrotic ectodermal dysplasia, a disorder characterized by defective formation of hair, sweat glands, and teeth in humans and in a mouse model, "Tabby" (Ta). The gene encodes ectodysplasin, a TNF ligand family member that activates the NF-kappaB-signaling pathway, but downstream targets and the mechanism of skin appendage formation have been only partially analyzed. Comparative transcription profiling of embryonic skin during hair follicle development in WT and Ta mice identified critical anhidrotic/hypohidrotic ectodermal dysplasia (EDA) effectors in four pathways, three already implicated in follicle formation. They included Shh and its effectors, as well as antagonists for the Wnt (Dkk4) and BMP (Sostdc1) pathways. The fourth pathway was unexpected, a variant NF-kappaB-signaling cascade based on lymphotoxin-beta (LTbeta)/RelB. Previously known to participate only in lymphoid organogenesis, LTbeta was enriched in developing hair follicles of WT but not in Ta mice. Furthermore, in mice lacking LTbeta, all three types of mouse hair were still formed, but all were structurally abnormal. Guard hairs became wavy and irregular, zigzag/auchen hairs lost their kinks, and in a phenocopy of features of Ta animals, the awl hairs doubled in number and were characteristically distorted and pinched. LTbeta-null mice that received WT bone marrow transplants maintained mutant hair phenotypes, consistent with autonomous LTbeta action in skin independent of its expression in lymphoid cells. Thus, as an EDA target, LTbeta regulates the form of hair in developing hair follicles; and when EDA is defective, failure of LTbeta activation can account for part of the Ta phenotype.
Asunto(s)
Folículo Piloso/crecimiento & desarrollo , Cabello , Linfotoxina-alfa/metabolismo , Proteínas de la Membrana/metabolismo , Factores de Necrosis Tumoral/metabolismo , Animales , Trasplante de Médula Ósea , Displasia Ectodérmica/genética , Displasia Ectodérmica/patología , Ectodisplasinas , Embrión de Mamíferos/anatomía & histología , Embrión de Mamíferos/fisiología , Femenino , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Cabello/anatomía & histología , Cabello/crecimiento & desarrollo , Folículo Piloso/citología , Proteínas Hedgehog , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Linfotoxina-alfa/genética , Linfotoxina beta , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Fenotipo , Embarazo , Transducción de Señal/fisiología , Piel/anatomía & histología , Piel/embriología , Glándulas Sudoríparas/citología , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/fisiología , Transactivadores/genética , Transactivadores/metabolismo , Factores de Necrosis Tumoral/genéticaRESUMEN
Choline uptake by the high affinity choline transporter (CHT) is the rate-limiting step in acetylcholine synthesis. Induction of CHT is therefore a critical step in cholinergic differentiation, and we examined the developmental expression of CHT in cholinergic sympathetic neurons that innervate rodent sweat glands. During postnatal development the earliest sympathetic axons in the rear footpads are noradrenergic, containing intense tyrosine hydroxylase immunoreactivity and lacking CHT-immunoreactivity (CHT-IR). By postnatal day 7 (P7) in mouse, and P10 in rat, weak CHT-IR appeared in axons associated with the sweat gland anlagen. CHT staining intensity increased during the following weeks in conjunction with plexus arborization and gland maturation. The pattern of CHT-immunoreactivity (CHT-IR) in the sweat gland innervation was similar to staining for the vesicular acetylcholine transporter and vasoactive intestinal peptide. Immunoblots of tissue from sympathectomized rats confirmed that most of the CHT in footpad was contained in sympathetic neurons. Although CHT expression has been reported in noradrenergic sympathetic neurons of the superior cervical ganglion, these data indicate that in the sympathetic neurons projecting to sweat glands CHT is present at detectable levels only after association with the glands.
Asunto(s)
Proteínas de Transporte de Membrana/biosíntesis , Neuronas/metabolismo , Sistema Nervioso Simpático/crecimiento & desarrollo , Sistema Nervioso Simpático/metabolismo , Animales , Axones/metabolismo , Western Blotting , Colina O-Acetiltransferasa/metabolismo , Femenino , Pie/inervación , Inmunohistoquímica , Ratones , Embarazo , Ratas , Ratas Sprague-Dawley , Ganglio Cervical Superior/metabolismo , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/inervación , Glándulas Sudoríparas/metabolismo , Simpatectomía Química , Sistema Nervioso Simpático/citología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Mutations in the human ectodysplasin-A (EDA) are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype, suggesting its vital role in the development of hair, sweat glands and teeth. Among several EDA splice isoforms, the most common and the longest EDA splice isoforms, EDA-A1 and EDA-A2, differing by only two amino acids, activate NF-kappaB-promoted transcription by binding to distinct receptors, EDAR and XEDAR. The extent to which any particular isoform is sufficient for the formation of hair, sweat glands or teeth has remained unclear. Here we report that transgenic expression of the mouse EDA-A1 isoform in tabby (EDA-less) males rescued development of several skin appendages. The transgenic tabby mice showed almost complete restoration of hair growth, dermal ridges, sweat glands and molars. The number of hair follicles in the transgenic mice is the same as in wild-type; though the development of follicles and associated glands varies from indistinguishable from wild-type to smaller and/or only partially formed. These results suggest that the other EDA isoforms may not be absolutely required for skin appendage formation, but consistent with distinctive temporal and spatial expression of the EDA-A2 isoform, are likely required for appropriate timing and completeness of development. Our data provide the first direct physiological evidence that EDA-A1 is a key regulator of hair follicle and sweat gland initiation; its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation.
Asunto(s)
Cabello/crecimiento & desarrollo , Proteínas de la Membrana/fisiología , Glándulas Sudoríparas/fisiología , Animales , Ectodisplasinas , Femenino , Cabello/fisiología , Humanos , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Estructura Terciaria de Proteína , Anomalías Cutáneas , Glándulas Sudoríparas/crecimiento & desarrollo , Cola (estructura animal) , Diente/crecimiento & desarrollo , Anomalías DentariasRESUMEN
The sympathetic innervation of sweat glands undergoes a developmental change in transmitter phenotype from catecholaminergic to cholinergic. Acetylcholine elicits sweating and is necessary for development and maintenance of secretory responsiveness, the ability of glands to produce sweat after nerve stimulation or agonist administration. To determine whether catecholamines play a role in the development or function of this system, we examined the onset of secretory responsiveness in two transgenic mouse lines, one albino and the other pigmented, that lack tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Although both lines lack TH, their catecholamine levels differ because tyrosinase in pigmented mice serves as an alternative source for catecholamine synthesis (Rios et al., 1999). At postnatal day 21 (P21), 28 glands on average are active in interdigital hind footpads of albino TH wild-type mice. In contrast, fewer than one gland is active in albino TH null mice, which lack catecholamines in gland innervation. Treatment of albino TH null mice with DOPA, a catecholamine precursor, from P11 to P21 increases the number of active glands to 14. Pigmented TH null mice, which have faint catecholamine fluorescence in the developing gland innervation, possess 12 active glands at P21, indicating that catecholamines made via tyrosinase, albeit reduced from wild-type levels, support development of responsiveness. Gland formation and the appearance of cholinergic markers occur normally in albino TH null mice, suggesting that catecholamines act directly on gland cells to trigger their final differentiation and to induce responsiveness. Thus, catecholamines, like acetylcholine, are essential for the development of secretory responsiveness.
Asunto(s)
Catecolaminas/metabolismo , Glándulas Sudoríparas/metabolismo , Acetilcolina/metabolismo , Acetilcolina/farmacología , Animales , Catecolaminas/farmacología , Dihidroxifenilalanina/metabolismo , Dihidroxifenilalanina/farmacología , Melanocitos/citología , Melanocitos/enzimología , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Monofenol Monooxigenasa/metabolismo , Agonistas Muscarínicos/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Pilocarpina/farmacología , Glándulas Sudoríparas/efectos de los fármacos , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/inervación , Tirosina 3-Monooxigenasa/genética , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Sweat glands are innervated by sympathetic neurons which undergo a change in transmitter phenotype from noradrenergic to cholinergic during development. As soon as the glands begin to differentiate, M3 muscarinic receptor mRNA and binding sites are detectable. Receptor expression appears in the absence of innervation and is maintained after denervation. While receptor expression is not regulated by innervation, secretory responsiveness is. Muscarinic blockade during development or in adult animals results in the loss of responsiveness and its reappearance requires several days. Cholinergic muscarinic activation is most likely to regulate one or more steps in the signalling cascade that are downstream of calcium mobilization. The anterograde regulation of sweat gland responsiveness is one facet of the reciprocal interactions are required to establish a functional synapse in this system.
Asunto(s)
Receptores Muscarínicos/metabolismo , Glándulas Sudoríparas/fisiología , Acetilcolina/metabolismo , Animales , Diferenciación Celular , Antagonistas Muscarínicos/farmacología , Ratas , Transducción de Señal , Glándulas Sudoríparas/efectos de los fármacos , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/inervación , Glándulas Sudoríparas/metabolismoRESUMEN
Descriptive studies have delineated a developmental change in neurotransmitter phenotype from noradrenergic to cholinergic in the sympathetic innervation of sweat glands in rodent footpads. Transplantation and culture experiments provide evidence that interactions with the target tissue induce this change. Recent studies with an antiserum that recognizes the vesicular acetylcholine transporter (VAChT) suggest, however, that the development of cholinergic function in sympathetic neurons, including those that innervate sweat glands, occurs prior to and does not require target contact. To clarify these apparently contradictory findings, we directly compared the appearance of VAChT immunoreactivity in the sympathetic neurons that innervate sweat glands with the time that axons contact this target. We find that VAChT immunoreactivity is not detectable in either the axons or cell bodies of sweat gland neurons until several days after target innervation. Before and during VAChT acquisition, the developing sweat gland innervation contains vesicular stores of catecholamines. An analysis of mutant mice that lack sweat glands was undertaken to determine whether VAChT expression requires target interactions and revealed that VAChT does not appear in the absence of glands. These findings, together with previous studies, confirm the target dependence of cholinergic function in the sympathetic neurons that innervate sweat glands.
Asunto(s)
Acetilcolina/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Transporte de Membrana , Glándulas Sudoríparas/inervación , Proteínas de Transporte Vesicular , Fibras Adrenérgicas/metabolismo , Animales , Proteínas Portadoras/genética , Inmunohistoquímica , Ratones , Ratones Mutantes , Ratones Transgénicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/metabolismo , Sistema Nervioso Simpático/crecimiento & desarrollo , Sistema Nervioso Simpático/metabolismo , Proteínas de Transporte Vesicular de AcetilcolinaAsunto(s)
Ganglios Simpáticos/metabolismo , Neuronas/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Animales , Colina O-Acetiltransferasa/metabolismo , Citocinas/metabolismo , Ganglios Simpáticos/citología , Ganglios Simpáticos/crecimiento & desarrollo , Inmunohistoquímica , Ratas , Ganglio Estrellado/citología , Ganglio Estrellado/crecimiento & desarrollo , Ganglio Estrellado/metabolismo , Ganglio Cervical Superior/citología , Ganglio Cervical Superior/crecimiento & desarrollo , Ganglio Cervical Superior/metabolismo , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/inervación , Glándulas Sudoríparas/metabolismoRESUMEN
To approach the mechanisms underlying the underdeveloped sweating responses of prepubertal boys, 8 boys (7-11 years old) and 11 men (21-25 years old) were exposed to a standard heat stress for 60 min. The test consisted of placing the subjects' lower legs into a 42 degrees C water bath while they sat in otherwise constant environmental conditions (ambient temperature 25 degrees C and 45% relative humidity). Rectal (T[re]) and skin temperatures, local sweating rates (mSW: on the chest, back, forearm and thigh) and the frequency of sweating expulsions (fSW: as an indicator of central sudomotor activity) were measured during the test. During the passive heating, no group differences were observed for the increase in T(re), mean skin temperature and metabolic heat production. However, mean body temperature (Tb) during heating was significantly higher for the boys (P < 0.001) because of a higher baseline T(re). The boys had lower mSW on the chest (P < 0.004) and thigh (P < 0.001) during the latter half of the 60-min exposure compared to the young men, although a similar mSW was observed between the groups during the first half of the test. The group difference of mSW on the back was similar to that of the chest and thigh, but the difference was not significant (P = 0.10). In contrast, the boys had a greater mSW on the forearm throughout the heating (P < 0.03). The slope of the mSW vs fSW relationship was significantly lower for the chest and thigh in the boys compared to the men (P < 0.05), and the same tendency was observed for the back (but was not significant, P = 0.10). In contrast, no difference was observed between the groups for the slope of mSW vs fSW for the forearm. Furthermore, a lower sweat output per gland was also observed on the chest, back, and thigh in the boys (P < 0.01), but not on the forearm. No group difference was observed for the slope of the fSW vs Tb relationship. These results suggest that the lower mSW observed in the prepubertal boys were due possibly to underdeveloped peripheral mechanisms, including the sweat glands and their surrounding tissues, rather than to an underdeveloped central drive activity related to sudomotor function. Regional differences may well exist in any underdeveloped peripheral mechanism associated with maturation.
Asunto(s)
Calor , Glándulas Sudoríparas/crecimiento & desarrollo , Glándulas Sudoríparas/fisiología , Sudoración/fisiología , Adulto , Envejecimiento/fisiología , Temperatura Corporal/fisiología , Niño , Humanos , Masculino , Consumo de Oxígeno/fisiología , Temperatura Cutánea/fisiologíaRESUMEN
The extrauterine development of marsupial pouch young (northern brown bandicoot Isoodon macrourus) has facilitated the study of the effects of murine epidermal growth factor (mEGF) on pattern formation in skin. Hair follicle initiation and development, which in the mouse would occur from about Days 13-14 of gestation onward, occurs postnatally. In the present study the effect in vivo of mEGF on developing skin corresponding to mouse gestational ages from Day 13 onward was examined. Subcutaneous injections of mEGF (0.5, 1.0 and 2.0 microg g[-1] body weight) or equivalent volumes of saline (0.9% w/w) were administered daily, before and during hair follicle initiation and development. Murine EGF inhibited the formation of hair follicles, hair follicle sweat glands, sebaceous glands and dermal papillae. The pattern of follicle initiation was perturbed. The characteristic trio follicle grouping was absent, and follicle rudiment densities (no. per mm2 skin surface) were significantly lower in animals treated with mEGF, whereas follicle diameters were increased. These data may reflect a role for the epidermal growth factor (EGF) receptor in epidermal pattern formation. The EGF receptor and its potential ligands (such as EGF, transforming growth factor (TGF-alpha) or other yet-to-be-discovered ligands) perhaps act as parts of a pattern-forming system in vertebrate skin.
Asunto(s)
Envejecimiento/fisiología , Factor de Crecimiento Epidérmico/farmacología , Folículo Piloso/crecimiento & desarrollo , Marsupiales/crecimiento & desarrollo , Piel/crecimiento & desarrollo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Factor de Crecimiento Epidérmico/administración & dosificación , Femenino , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Inyecciones Subcutáneas/veterinaria , Masculino , Ratones , Glándulas Sebáceas/crecimiento & desarrollo , Piel/efectos de los fármacos , Glándulas Sudoríparas/crecimiento & desarrolloRESUMEN
Matrix-degrading metalloproteinases play a major role in tissue remodeling. Recent studies have shown that enzymes of this class are constitutively expressed primarily by stromal cells and not by epithelium. Here we present immunohistochemical evidence that matrilysin is localized within epidermal cells in developing skin and in tumor cells of cutaneous malignancies. The expression of matrilysin protein in developing fetal skin (6-15 weeks) is localized primarily to the germinative basal cell layer of fetal epidermis and early appendageal buds. The buds continue to express matrilysin during mesenchymal invasion. As development progresses (15-19 weeks) matrilysin is concentrated only in cells at the distal portion of the invading follicular and sweat gland appendageal cords. In adult skin, matrilysin was localized specifically to the outer root sheath of the hair follicles and the secretory cells of the eccrine glands but was absent in the epidermis. Nodulocystic, keratotic, adenoid basal cell carcinomas (BCCs) did not express matrilysin. In contrast, in the more aggressive morpheaform (infiltrative) BCCs and recurrent BCCs, matrilysin was localized at the tumor-stromal interface. In squamous cell carcinomas matrilysin was present in tumor cells at the stromal interface surrounding the tumor nests. The demonstration of matrilysin protein in germinal basal cells during fetal skin development and its presence in tumor cells at the stromal junction suggests that this enzyme may contribute to the proteolytic activity associated with cell-extracellular matrix interactions during appendageal development and tumor invasion.
Asunto(s)
Metaloendopeptidasas/análisis , Neoplasias Cutáneas/enzimología , Piel/enzimología , Piel/crecimiento & desarrollo , Adulto , Desarrollo Embrionario y Fetal , Cabello/crecimiento & desarrollo , Humanos , Inmunohistoquímica , Metaloproteinasa 7 de la Matriz , Cuero Cabelludo/crecimiento & desarrollo , Piel/embriología , Neoplasias de las Glándulas Sudoríparas/enzimología , Glándulas Sudoríparas/enzimología , Glándulas Sudoríparas/crecimiento & desarrolloRESUMEN
Growth and differentiation of skin layers, hair follicles, and skin glands were studied in cattle of two genotypes during the period from early postnatal development until the age of 30 months. Development of skin and its derivatives was shown to proceed irregularly and include alternating periods characterized by an increase, temporary arrest, or even decrease of corresponding morphometric indices. On the basis of these data a conclusion is drawn that periodic changes in thickness of skin and its individual layers during ontogenesis are a natural phenomenon. It is suggested that a complex of morphometric indices can reflect specific characteristics of individual breeds and their productivity.