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[Sebaceous glands as transporters of vitamin E].

Human sebum is produced by sebaceous glands and reaches the skin surface via secretion through the hair shaft. There is experimental evidence that the sebaceous glands and sebum serve as a transport mechanism taking the lipophilic antioxidant vitamin E from the blood to the skin surface. The highest levels of vitamin E are found in the sebum and in the skin lipid film in sebum-rich areas such as facial skin. Recent studies indicate that daily oral supplementation of moderate doses of alpha-tocopherol for at least 3 weeks leads to significant increases of vitamin E levels in human skin sites with a high density of sebaceous glands, such as the face. Thus, the potential photoprotective and antioxidants effects of oral vitamin E, as well as possibly other antioxidants, are site-dependent. These findings should be considered when designing clinical studies to assess the efficacy of oral antioxidants against oxidative stress in the skin.

Acne Vulgaris↗

Neuropeptides and sebaceous glands.

This review provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. We show morphological alterations of sebaceous glands elicited by SP and differences in expression of various neurogenic factors in association with sebaceous glands in acne-prone versus normal facial skin. In vitro studies reveal that SP promotes both the proliferation and the differentiation of sebaceous glands. SP induces the expression of neutral endopeptidase, a potent neuropeptide-degrading enzyme, in sebaceous germinative cells and of E-selectin by perisebaceous venules. Facial skin from acne patients is characterized by rich innervation, by increased numbers of SP-containing nerves and mast cells, and by strong expression of neutral endopeptidase in sebaceous glands and E-selectin in venules around sebaceous glands, compared with normal skin. Mast cell-derived IL-6 and TNF-alpha, followed by SP-stimulated degranulation, have the potential to induce nerve growth factor expression by sebaceous cells which results in the promotion of innervation and in the expression of E-selectin, respectively. SP enhances mast cell proliferation through up-regulation of stem cell factor expression in fibroblasts. These findings suggest the involvement of neurogenic factors, such as neuropeptides, in the disease process of acne and explain the possible mechanism of the exacerbation of acne from a neurological point of view.

Acne Vulgaris↗

Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides.

Sebaceous wax esters and epidermal acylceramides were isolated from skin surface lipid obtained from children and from young adults. Fatty acid methyl esters (FAME) were prepared from the esterified fatty acids of these lipid classes and analyzed to ascertain the proportions of methyl linoleate (18:2 delta 9,12), methyl sebaleate (18:2 delta 5,8), and methyl sapienate (16:1 delta 6). On the same subjects, 2 measures of sebum secretion rate were obtained, namely the sustainable wax ester secretion rate (WESR) on the forehead and the ratio of wax esters/(cholesterol + cholesterol esters) [WE/(CH + CE)] in the surface lipid. The proportions of methyl linoleate in FAME from the wax esters decreased, and the proportions of methyl sebaleate increased, with increased rates of sebum secretion. For both methyl linoleate and methyl sebaleate, a better correlation was obtained when the ratio of WE/(CH + CE) was used as a measure of sebum secretion rather than the WESR. The proportions of methyl linoleate in the FAME from the acylceramides were also inversely related to ratios of WE/(CH + CE). In acylceramides, linoleate was replaced by sapienate, a major fatty acid of human sebum. It appears, therefore, that sebum fatty acid composition may change with changes in sebaceous gland activity, and that sebum fatty acids can enter the epidermis and be incorporated into epidermal lipids.

Acne Vulgaris↗

The melanocortin 5 receptor is expressed in human sebaceous glands and rat preputial cells.

Melanocortins regulate pigmentation, adrenal hormone secretion, immune functions, lipid metabolism, and feeding behaviors in rodents. These peptides include adrenocorticotrophic hormone, melanocyte stimulating hormone, beta-lipotrophin, and the endorphins. Lipid metabolism in sebaceous glands and preputial glands of rodents is regulated by alpha-melanocyte stimulating hormone, the major agonist for melanocortin receptors. Five melanocortin receptor subtypes have been identified that differ in their tissue localization and affinities for melanocortin ligands. Targeted disruption of the melanocortin 5 receptor in transgenic mice results in widespread dysfunction of exocrine glands, including a marked decrease in sebum production. A role for melanocortins in the modulation of human sebum production has not been established. The goal of this study is to determine which melanocortin receptors are expressed in human sebaceous glands. Messenger RNA was isolated from human sebaceous glands and the reverse transcriptase polymerase chain reaction was performed using primers specific for each of the melanocortin receptor subtypes. Transcripts were detected for the melanocortin 5 receptor. A polyclonal chicken antihuman antibody to the melanocortin 5 receptor localized to sebaceous glands, eccrine glands, hair follicles, and epidermis in human skin, rat skin, cultured human sebocytes, and rat preputial cells. Presence of the melanocortin 5 receptor protein in human sebaceous glands and rat preputial glands was further verified by Western blotting. These data support further investigation of the role of melanocortins in the regulation of human sebum production and support the use of the rat preputial system as an experimental model in sebaceous gland physiology.

Animals↗

Giant solitary sebaceous gland hyperplasia clinically simulating epidermoid cyst.

We report an unusual case of sebaceous gland hyperplasia manifested clinically as a large solitary intracutaneous nodule, which was at first diagnosed as an epidermoid cyst. Histologically, the nodule consisted of a single large central cavity connected with numerous fully-matured sebaceous glands. We discuss the unique clinical appearance and its histopathological differential diagnosis including sebaceous adenoma, sebaceous trichofolliculoma, organoid nevus and sebaceous gland hyperplasia.

Diagnosis, Differential↗

Cell proliferation kinetics of epidermis and sebaceous glands in relation to chalone action.

Median S-phase lengths of pinna epidermis and sebaceous glands, and of epithelia from the oesophagus and under surface of the tongue of Albino Swiss S mice were estimated by the percentage labelled mitoses method (PLM). The 18.4 and 18,8 hr for the median length of S-phase for pinna epidermis and sebaceous glands respectively made it possible for these two tissues to be used experimentally for testing tissue specificity in chalone assay experiments. The 10.0 and 11.5 hr for oesophagus ang tongue epithelium respectively made experimental design for chalone assay difficult when pinna epidermis was the target tissue. The results of the Labelling Index measured each hour throughout a 24-hr period showed no distinct single peaked diurnal rhythm for pinna epidermis and sebaceous glands. Instead a circadian rhythm with several small peaks occurred which would be expected if an S-phase of approximately 18 hr was imposed on the diurnal rhythm. This indicates that there may be very little change in the rate of DNA synthesis. The results are given for the assay in vivo of purified epidermal G1 and G2 chalones, and the 72--81% ethanol precipitate of pig skin from which they could be isolated. These experiments were performed over a time period which took into account the diurnal rhythm of activity of the mice as well as the S-phase lengths. Extrapolating the results with time of action of the chalone shows that the G1 chalone acts at the point of entry into DNA synthesis and that the S-phase length was approximately 17 hr for both the pinna epidermis and sebaceous glands. This may be a more correct value since the PLM method overestimates the median S-phase length as it is known that in pinna skin the [3H]TdR is available to the tissues for 2 hr and true flash labelling does not take place. The previous reports that epidermal G1 chalone acts some hours prior to entry into S-phase resulted from experiments on back skin where the S-phase is shorter and there is a pronounced diurnal rhythm which could mask the chalone effect. The epidermal G2 chalone had no effect on DNA synthesis even at different times in the circadian rhythm. Thus the circadian rhythms and S-phase lengths of the test tissues need to be considered when experiments are performed with chalones. Ideally, the target tissues selected for cell line specificity tests should have the same cell kinetics for the easier and more accurate assessment and interpretation of results. When the tissues have markedly different cell kinetics, experimental procedures and results need to be evaluated accordingly. The point of action of G1 chalone can only be assessed if the effect is measured over the peak of incorporation of [3H]TdR into DNA. The results of the effects of skin extracts are analysed in relation to changes in the availability of [3H]TdR for the incorporation into DNA and to the possibility of there being two distinct populations of proliferating cells.

Animals↗

Common presentations of sebaceous gland carcinoma of the eyelid.

Carcinoma of the sebaceous glands of the eyelid is a malignant lesion bearing a close resemblance to other less aggressive lid lesions. A long period of time often elapses between initial presentation and correct diagnosis and treatment. Three cases are presented to illustrate common presentations of sebaceous gland carcinoma.

Aged↗

[Hyperplasia of sebaceous glands (Fordyce's disease) in an oral mucocutaneous graft: 45-year follow-up].

BACKGROUND: Diffuse sebaceous gland hyperplasia in transplanted buccal mucosa is a very rare condition. We report on a further patient with this entity. PATIENT: In 1953, a now 68-year-old man suffered a severe alkali burn. Transplantation of oral mucosa was performed that same day in order to prevent perforation of the eye. Over the following 45 years, the patient developed multiple yellowish nodules within the grafts. Histologically, these nodules proved to be normally differentiated sebaceous glands. CONCLUSIONS: Diffuse sebaceous gland hyperplasia originating from within oral mucosa and developing over an extended period of time is a clinical entity known as Fordyce's disease. It is this a late complication of mucocutaneous transplantation, and although it constitutes mainly a problem of cosmesis, functionally it can lead to aberrant secretion of sebum.

Aged↗

Dependence of fetal hairs and sebaceous glands on fetal adrenal cortex and possible control from adrenal medulla.

Human fetal adrenal development is characterized by rapid growth, high steroidogenic activity, and a distinct morphology, including a unique cortical compartment known as the fetal zone. For most of gestation, the predominant fetal zone accounts for 80-90% of the cortical volume and is the primary site of growth and steroidogenesis, producing 100-200 mg/day of the androgenic steroid, dehydroepiandrosterone sulfate (DHEA-S). The physiological role of this zone during intrauterine life is not well understood. While the glands appear to be capable of DHEA-S synthesis early in gestation (8-10 weeks), we noticed that this event precedes the differentiation of hairs and sebaceous glands. Hairs begin to develop between 9 and 12 weeks and sebaceous glands between 13 and 15 weeks of gestation. Sebaceous glands form an oily secretion - sebum that mixes with desquamated epidermal cells to form vernix caseosa. Vernix caseosa protects the developing skin from constant exposure to amniotic fluid, and hairs helps to hold the vernix caseosa on the skin. We suggest therefore that the human fetal adrenal cortex produces DHEA-S beginning at around 8-10 weeks of gestation in sufficient quantities to influence the growth of hairs and sebaceous glands. Soon after birth, the fetal zone atrophies, and adrenal androgen production decreases to minimal levels. As a consequence, in concordance with the rapid decrease in adrenal androgen levels and in consistent with our hypothesis, fetal hairs are shed and sebaceous glands shrink to small structures. The mechanism that regulates fetal adrenal androgen production is a key unanswered problem in human adrenal biology. Since there exists a close relationship between epinephrine and DHEA-S levels during adrenarche which shows modulatory interactions between adrenal androgen production and adrenomedullary function, we suggest again that adrenomedullary function might play a role in the control of fetal adrenal androgen secretion.

Adrenal Cortex↗

Outcome of periocular sebaceous gland carcinoma.

PURPOSE: To determine the long-term outcome of periocular sebaceous gland carcinoma and factors predictive of tumor recurrence. METHODS: A retrospective case note review of all patients with periocular sebaceous gland carcinoma treated at the Queen's Medical Centre, Nottingham, United Kingdom, between 1992 and 1999. Patient age at time of surgery, tumor location, and treatment were recorded. The tumor dimensions and histopathologic description were correlated with tumor recurrence. The general practitioners were contacted to determine whether there had been any further tumor recurrences since the last entry in the hospital notes. RESULTS: A total of 11 cases (mean age, 75 years) were reviewed, of which 7 were female. The eyelids were involved in all but 2 cases, and maximum tumor dimension ranged from 6 to 25 mm. Three demonstrated pagetoid spread. Recurrence was seen in all tumors reported as incompletely excised (4 cases), of which only one demonstrated pagetoid spread. Tumour size was not predictive of recurrence. CONCLUSIONS: In our unit, the best prognostic factor for sebaceous gland carcinoma is a histologic report confirming complete excision of the tumor, whatever the tumor size or pattern of spread identified.

Adenocarcinoma, Sebaceous↗

Glycoproteins of the carcinoembryonic antigen (CEA) family are expressed in sweat and sebaceous glands of human fetal and adult skin.

The carcinoembryonic antigen (CEA) family comprises a group of glycoproteins including the classical CEA, nonspecific cross-reacting antigens (NCA), and biliary glycoprotein (BGP). CEA glycoproteins have been identified in many glandular and mucosal tissues. In view of their putative role in cell adhesion, protein sorting, and signal transduction, CEA glycoproteins are thought to be involved in embryogenesis, architectual integrity, and secretory mechanisms of glandular epithelia. Since there are few data available on the expression of CEA-like proteins in human skin, the aim of this study was to immunohistochemically specify and localize the CEA glycoproteins in cutaneous adult and fetal glands using a panel of well-characterized antibodies. The secretory parts of eccrine sweat glands expressed CEA, NCA-90, and BGP, whereas apocrine glands remained unreactive for CEA glycoproteins. The ductal epithelia of both eccrine and apocrine glands contained CEA and NCA-90. Sebaceous glands were stained for BGP only. Electron microscopy of sweat glands showed CEA glycoprotein expression in cytoplasmic organelles and on microvilli lining the ductal surface. In sebaceous glands, BGP were demonstrated in small vesicles and along the cell membranes of differentiating sebocytes. Fetal development of cutaneous glands was associated with early expression of CEA glycoproteins. Additionally, mice transgenic for human CEA were shown to express CEA in sweat glands. The overall distribution of CEA glycoproteins in cutaneous glands was consistent with that in epithelia of other glandular tissues.

Adult↗

Exclusive androgenic effect of dehydroepiandrosterone in sebaceous glands of rat skin.

In order to analyze the hormonal effects of dehydroepiandrosterone (DHEA) in skin sebaceous glands, the precursor steroid was administered to ovariectomized (OVX) female Sprague-Dawley rats at a dose of 30 mg applied on the dorsal skin, twice daily, for 3, 6 and 12 months. In a parallel experiment, female OVX rats were treated with DHEA at the same daily percutaneous dose of 30 mg, alone or in combination with the antiandrogen Flutamide or the pure antiestrogen EM-800, for 12 months, in order to determine the androgenic and/or estrogenic components of DHEA action. Treatment of female OVX rats with DHEA resulted in a similar mild to moderate hyperplasia of the sebaceous glands of both dorsal (site of application) and ventral skin, as illustrated by an increase in the number and size of the acini. The above-indicated effects were observed at all time intervals studied, beginning at 3 months of treatment, and they were not further increased after longer term administration of DHEA (for 6 and 12 months). The addition of Flutamide to DHEA treatment completely prevented the DHEA-induced changes in the sebaceous glands, whereas the antiestrogen EM-800 had no effect. The present data indicate an exclusive androgenic stimulatory action of DHEA on the sebaceous glands, thus pointing out the importance of local intracrine DHEA transformation into androgens for skin anatomical integrity and function, while showing that estrogens, if active in rat skin, do not originate from DHEA.

Administration, Cutaneous↗

Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro.

BACKGROUND: Nuclear hormone receptors are important in the regulation of epidermal differentiation and have been implicated in lipid metabolism. In particular, there is evidence suggesting that the activation of peroxisome proliferator-activated receptors (PPARs) is an important factor in the regulation of sebocyte lipogenesis. OBJECTIVES: To determine the role of PPARs, farnesoid X receptor (FXR) and other orphan nuclear hormone receptors in sebaceous gland function in vitro by investigating the biochemical effects of appropriate ligands, and by establishing the RNA and protein expression patterns of a number of nuclear receptors in sebaceous glands ex vivo. METHODS: Human chest sebaceous glands were maintained in vitro as freshly isolated and as 7-day cultured whole organs. We then studied the effects of appropriate ligands on the glandular rates of lipogenesis and DNA synthesis, as well as determining the mRNA (reverse transcription-polymerase chain reaction) and protein expression patterns (immunohistochemistry/immunoblotting) of the nuclear hormone receptors of interest. RESULTS: PPAR ligands, but not FXR ligands, inhibited sebaceous lipogenesis, in particular the PPARalpha ligands LY 171883 and WY 14643, and the PPARgamma ligands BRL 49653 and 15-deoxy-Delta-12,14-prostaglandin J(2). We detected RNA expression of PPARalpha, PPARbeta, PPARgamma, retinoid X receptor alpha, liver X receptor alpha (LXRalpha) and pregnane X receptor but not FXR in freshly isolated and 7-day maintained sebaceous glands. PPARalpha, PPARbeta, PPARgamma and LXRalpha protein were detected in nuclear extracts of sebaceous glands. CONCLUSIONS: We conclude that activation of nuclear hormone receptors, in particular activation of PPARalpha and PPARgamma, can regulate lipogenesis in human sebaceous glands. As suppression of sebum secretion is associated with reduced acne activity, the nuclear hormone receptors involved may open new avenues in the development of novel acne treatments.

Cell Differentiation↗

Organ maintenance of human sebaceous glands: in vitro effects of 13-cis retinoic acid and testosterone.

Human sebaceous glands were isolated by shearing, and maintained for 7 days either on defined medium, on medium supplemented with 3 microM-testosterone or on medium supplemented with both 3 microM-testosterone and 1 microM-13-cis retinoic acid. Freshly isolated glands retained their in vivo morphology. On maintenance, the glands retained their freshly isolated rates of cell division, but the sebocytes showed increased keratinization and there was multilayering of the peripheral undifferentiated cells. However, glands maintained in the presence of 1 microM-13-cis retinoic acid showed very little luminal keratinization and only a small degree of multilayering. On autoradiography, freshly isolated glands retained their in vivo pattern of [methyl-3H]thymidine incorporation. Similar patterns were seen when glands were maintained for 7 days with or without testosterone. However, in the presence of both testosterone and 13-cis retinoic acid there was only slight graining. Following 7 days maintenance the rate of lipogenesis fell significantly. This was partially reversed by testosterone, but further inhibited by 13-cis retinoic acid. The patterns of lipids that are synthesised after a week's maintenance are very similar to those seen in freshly isolated glands, except that the squalene:cholesterol ratio is reversibly regulated by 3 microM-testosterone and 1 microM-retinoic acid. Protein synthesis was maintained at the same rates as for freshly isolated glands under all conditions of maintenance. Whereas DNA synthetic rates were maintained in the presence of testosterone, they were significantly inhibited by 13-cis retinoic acid. Glandular wet weights were retained under all conditions of maintenance, except that they were significantly reduced by 13-cis retinoic acid. This study shows that human sebocytes continue to divide on organ maintenance, but that they do not differentiate fully. However, this provides the first demonstration that 13-cis retinoic acid acts on human sebaceous glands directly, reducing the rate of cell division and the rate of lipogenesis, which shows that the maintained human sebaceous gland might provide a useful model for studying the effect of 13-cis retinoic acid on human sebocytes.

Adult↗

[Structure of the inguinal gland in the mountain hare in various states of reproductive activity. I. The sebaceous glands].

Histology and ultrastructure of sebaceous glands of the integumental inguinal gland of the hare were studied during the periods of low and high reproductive activity (in winter and in spring breeding season). It was established that the glands were functioning continually (cells in acini of all the animals used contained numerous secretory granules). The expansion of agranular endoplasmic reticulum and Golgi complex in secretory cells of sexually active animals, especially of males, shows an increased intensity of gland secretory process during the breeding season.

Animals↗

New findings on the proteins of sebaceous glands.

In order to understand the distribution and concentration of proteins with -SH groups or S-S linkages in sebaceous cells during differentiation and holocrine secretion of sebaceous glands, skin specimens from the inner side of ears of New Zealand white rabbits were examined histochemically and ultrastructurally. DACM (N-[7-dimethylamino-4-methyl-3-coumarinyl] maleimide) staining method showed that proteins containing -SH groups were present in the cells (cytoplasm and nuclei) in all layers from the peripheral to the terminally differentiated cells of sebaceous glands and that proteins containing S-S linkages were present in the terminally differentiated cells and their pyknotic nuclei but not in the peripheral and differentiating cells of sebaceous glands. Lipid droplets in all sebaceous cells contained neither -SH groups nor S-S linkages. Ultrastructurally, the terminally differentiated cells were very electron dense and seemed to be abruptly formed from the differentiating cells that were producing lipid droplets. These findings indicate that the conversion of -SH groups to S-S linkages of proteins also occurs in sebaceous glands as in epidermis and hair.

Animals↗

Mechanism of L-arginine-induced sebaceous gland hyperplasia in rats.

OBJECTIVE: To study the effect of L-arginine (L-arg) on the sebaceous gland of SD rat. METHODS: The SD rats of different sexes and ages were subjected to intragastric administration of L-arg at 10 mg.kg(-1).d(-1) (L-arg group) or saline (saline group) for 14 days. Blood samples were obtained from these rats for serum androgen determination and the pathological changes of the skin were observed. RESULTS: After L-arg treatment for 7 days, the dorsal hair of all the adult male rats appeared damp, greasy and yellow, while that of the adult and 5-week-old female rats looked normal. When the treatment was prolonged to 14 days, the same changes occurred in most of the adult female rats and all the 5-week-old female rats. The sebaceous glands of the abnormal skin showed hyperplasia in pathologic examination. The serum levels of androgen in rats with sebaceous gland hyperplasia were significantly higher than those in the control rats. CONCLUSION: L-arg can promote sebaceous gland hyperplasia in rats in relation to increased androgen secretion induced by L-arg and NO.

Androgens↗

Sebaceous gland adenomas in dogs.

In a review of neoplasm registry records at Kansas State University (1961 through 1971), 162 sebaceous gland adenomas were reported in 31 breeds of dogs, representing 5.0% of 3,240 neoplasms recorded. Mean age of the affected dogs was 9.5 years. Females accounted for 56.1% of the recorded sebaceous gland adenomas. The tumors were removed surgically for biopsy in all dogs; 24 dogs had multiple concurrent skin neoplasms of a different cell type, and 7 dogs had recurrence of sebaceous gland adenomas, without metastases, and required further surgery. The skin of the hindquarters, abdomen, and thorax was a principal site (54%) of the sebaceous gland adenomas.

Adenoma↗