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[Giant sebaceous gland hyperplasia of the vulva].

BACKGROUND: Sebaceous gland hyperplasia is an epithelial tumour with sebaceous differentiation. Genital involvement is rare. In this paper, we report a new case of sebaceous gland hyperplasia of the vulva. CASE REPORT: A 27 year-old woman presented multiple polypoid lesions of the lower third of left labium majus. The lesions were soft to the touch, measured 5 cm in length and were painless. The cutaneous biopsy confirmed the diagnosis of sebaceous gland hyperplasia of the vulva. Surgical excision was performed in two separate procedures and was successful. DISCUSSION: This case was unusual in terms of the site, the clinical appearance and the weeping seen due to the high concentration of hyperplasic sebaceous glands.

Adult↗

Sebaceous gland hyperplasia of the vulva.

BACKGROUND: Sebaceous gland hyperplasia is a common condition of the face in elderly patients. We report a case of sebaceous gland hyperplasia on the vulva. CASE: A 19-year-old woman presented with a polypoid tumor on her left labium majus of which the greatest diameter was 2.5 cm, covered by normal appearing skin. Histologic examination revealed a sebaceous gland hyperplasia. Immunohistochemical techniques showed high expression of androgen receptors on sebaceous cells. CONCLUSION: Clinical and gross features of the two documented cases of sebaceous gland hyperplasia on the vulva are different from those of typical lesions on the face. Histologic study of a vulvar biopsy is required to reach a specific diagnosis of this hamartomatous benign condition.

Adult↗

Acne and sebaceous gland function.

The embryologic development of the human sebaceous gland is closely related to the differentiation of the hair follicle and the epidermis. The number of sebaceous glands remains approximately the same throughout life, whereas their size tends to increase with age. The development and function of the sebaceous gland in the fetal and neonatal periods appear to be regulated by maternal androgens and by endogenous steroid synthesis, as well as by other morphogens. The most apparent function of the glands is to excrete sebum. A strong increase in sebum excretion occurs a few hours after birth; this peaks during the first week and slowly subsides thereafter. A new rise takes place at about age 9 years with adrenarche and continues up to age 17 years, when the adult level is reached. The sebaceous gland is an important formation site of active androgens. Androgens are well known for their effects on sebum excretion, whereas terminal sebocyte differentiation is assisted by peroxisome proliferator-activated receptor ligands. Estrogens, glucocorticoids, and prolactin also influence sebaceous gland function. In addition, stress-sensing cutaneous signals lead to the production and release of corticotrophin-releasing hormone from dermal nerves and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar lipids. Among other lipid fractions, sebaceous glands have been shown to synthesize considerable amounts of free fatty acids without exogenous influence. Sebaceous lipids are responsible for the three-dimensional skin surface lipid organization. Contributing to the integrity of the skin barrier. They also exhibit strong innate antimicrobial activity, transport antioxidants to the skin surface, and express proinflammatory and anti-inflammatory properties. Acne in childhood has been suggested to be strongly associated with the development of severe acne during adolescence. Increased sebum excretion is a major factor in the pathophysiology of acne vulgaris. Other sebaceous gland functions are also associated with the development of acne, including sebaceous proinflammatory lipids; different cytokines produced locally; periglandular peptides and neuropeptides, such as corticotrophin-releasing hormone, which is produced by sebocytes; and substance P, which is expressed in the nerve endings at the vicinity of healthy-looking glands of acne patients. Current data indicate that acne vulgaris may be a primary inflammatory disease. Future drugs developed to treat acne not only should reduce sebum production and Propionibacterium acnes populations, but also should be targeted to reduce proinflammatory lipids in sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and inhibit leukotriene B(4)-induced accumulation of inflammatory cells. They should also influence peroxisome proliferator-activated receptor regulation. Isotretinoin is still the most active available drug for the treatment of severe acne.

Acne Vulgaris↗

The quantification and distribution of nasal sebaceous glands using image analysis.

The distribution of sebaceous glands in nasal skin is of interest because the presence of these adnexal structures significantly influences the outcome of healing. Using whole nasal skins dissected from cadavers, we prepared tissue sections from the nasal bridge to the nasal tip, both from the midline and lateral aspects. The sebaceous glands in these sections were analyzed for the following parameters: (1) size of the glands, (2) width of luminal cross-sections, and (3) depth of the glands. These parameters were studied using a Leitz Quantimet 500 Plus image analyzer and software to quantify the results. We found that the superior or proximal nasal skin contains fewer, smaller, more superficially located sebaceous glands. The inferior or distal nasal skin contains increased numbers of sebaceous glands which are markedly larger in size. The glands in the distal nose have larger lumina, are situated both superficially and deep in the dermis, and also occupy a greater percentage of the dermis. We identified an anatomical breakpoint on the nasal skin, marking the transition from superficial, small sebaceous glands to superficial-and-deep, enlarged glands. The columella was found to be similar to the proximal nasal skin.

Humans↗

Increased androgen binding capacity in sebaceous glands in scalp of male-pattern baldness.

Sebaceous glands were isolated by manual dissection under a microscope from surgical specimens of scalp skin with male pattern baldness and skin specimens of hairy and bald scalp obtained at autopsy. The 800 X g pellet (nuclear fraction) and the 164,000 X g supernatant fraction (cytosol) of homogenates of the sebaceous glands were used for measurements of androgen binding characteristics, using dextran-coated charcoal and sucrose gradient methods. Scatchard plots showed high affinity binding for [3H]dihydrotestosterone (DHT) and [3H]methyltrienolone (R1881). Nuclei prepared from bald scalp contained greater total androgen binding capacity than nuclei of hairy scalp, although Kd values of type I binding were similar (0.68 vs 0.56 nM, respectively). On sucrose gradient, the binding protein from cytosol was found in the 7 to 8S density range. Androgen binding by cytosol of sebaceous glands of hairy scalp had Kd of 1.89 +/- .79 and 2.05 +/- .56 nM for DHT and R1881, respectively, and Bmax of 18.7 +/- 4.4 and 20.0 +/- 4.6 fmol/mg protein for DHT and R1881, respectively. Cytosol from sebaceous glands of bald scalp had Kd values approximately half those of hairy scalp, and Bmax values 50%-100% higher. The bound 3H labeled DHT and R1881 could be partially displaced by testosterone (40-50%), moxestrol (28-32%), promegestone (19-26%), and delta 4-androstenedione (6-12%), but not by dehydroepiandrosterone. These data demonstrate the presence of specific androgen binding protein in sebaceous glands, and that sebaceous glands of bald scalp have greater binding affinity and capacity for androgens than those in hairy scalp. This difference may explain the greater androgenic response in androgenic alopecia.

Adult↗

Side gland of Suncus murinus as a new model of sebaceous gland: 5 alpha-reductase, androgen receptor, and nuclear androgen content in male and female animals.

The side gland of Suncus murinus is composed of well-developed sebaceous glands in both males and females. We measured the 5 alpha-reductase activity, androgen receptor content, and the intranuclear concentrations of testosterone and dihydrotestosterone in this side gland taking it as a new experimental model of human sebaceous glands. Lineweaver-Burk plot analysis suggested the presence of two classes of 5 alpha-reductase with different Km for testosterone in the homogenate. The enzyme activity was slightly higher in males than in females in the presence of a high concentration of testosterone. The levels of androgen receptors were approximately 40 and 30 fmol/mg protein in the cytosol and nuclei, respectively. The values did not differ significantly between males and females. The intranuclear concentration of dihydrotestosterone in the side gland was higher than that of testosterone in each sex. The intranuclear level of each of these two androgens in the female side gland was comparable to that in the male side gland despite the fact that the serum level of testosterone was much lower in the female. These data clearly indicate that the side gland is a typical target tissue for androgens in the female as well as in the male. Androgens other than testosterone may serve as precursors of dihydrotestosterone in the female side gland.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Circumscribed sebaceous gland hyperplasia: autoradiographic and histoplanimetric studies.

Circumscribed sebaceous gland hyperplasia (sebaceous hyperplasia) is a common benign facial tumor found in adults and aged. Seventeen biopsies of sebaceous hyperplasia from 10 patients, females and males aged 57-87 years were secured which were injected 45 min or up to 15 days prior with tritiated thymidine, and prepared for autoradiography. Specimens were evaluated by cell counts (labeling index, labeled total cells), and histoplanimetric techniques (sagittal section areas and circumference of sebaceous hyperplasia, of sebocytes, and of sebocyte nuclei). Controls were uninvolved sebaceous follicles from the same subjects, from an age-matched group, and from young male adults. In sebaceous hyperplasia the labeling index of basal cells is low with 5.7% +/- 2.3 vs uninvolved sebaceous follicles from the same subject (8.6% +/- 2.4) and the younger subjects with a value of 10.1% +/- 2.0). Labeled cells are retained in the acini much longer than in young adults (slowed down transit and turnover time). The glands of sebaceous hyperplasia are very large, their sebocytes are small, and many more basal cells are found per unit basement membrane length.

Adenoma↗

Sebaceous glands within the thymus: report of three cases.

Sebaceous glands in the thymus were discovered in three patients--two with myasthenia gravis and the other, who was operated on because of aortic valvular disease--with an unsuspected thymoma. Sebaceous glands not associated with hair follicles occur in diverse sites, the majority of which are in the head and neck or anogenital regions. Although most of these sites arise from the ectoderm, sebaceous glands have been reported in a thyroglossal duct, the larynx, and the esophagus, which are entodermal structures. Thus, precedents for ectodermally derived sebaceous glands in endodermal sites exist, but sebaceous glands have not previously been reported in the thymus. The authors speculate that their occurrence in the thymus may be related to the reported ectodermal contribution to the developing thymus by the epibranchial placode or cervical sinus.

Adult↗

The fatty acids of human sebaceous gland phosphatidylcholine.

The fatty acids of human sebaceous gland phosphatidylcholine were examined by gas chromatography and by analysis of the double bond positions in the C-16 and C-18 monoenes. Compared to phosphatidylcholine from other organs, sebaceous gland phosphatidylcholine was found to be deficient in essential fatty acids and poly-unsaturated fatty acids. The relatively large mono-unsaturated fatty acid fraction consisted predominantly of fatty acids with delta6- and delta8-unsaturation. Analysis indicates that the fatty acids of sebaceous gland phospholipids are predominantly of types synthesized in sebaceous glands.

Fatty Acids↗

Control and function of sebaceous glands.

This review describes the various types of sebaceous glands, their locations, and where possible their different functions. All sebaceous glands are similar in structure and secrete sebum by a holocrine process. However, the nature of this secretion and the regulation of the secretory process seem to differ among the various types of glands. Methods for measuring sebum secretion and assessing sebaceous gland activity are also described. The area of major interest during the last 20 years has undoubtedly been the mechanisms that control sebaceous gland function. Most studies have focused on the endocrine control and in particular on the role of androgens and pituitary hormones, although evidence suggests that nonendocrine factors may also be important. However, many questions remain and during the next few years attention will certainly be given to the role of retinoids and their mode of action in the treatment of acne.

Animals↗

Prognostic value of immunohistochemical staining for proliferating cell nuclear antigen, p53, and c-erbB-2 in sebaceous gland carcinoma and sweat gland carcinoma: comparison with histopathological parameter.

Thirteen cases of sebaceous gland carcinoma and 10 cases of sweat gland carcinoma were studied using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), c-erbB-2, and p53 to examine correlations among them, and to determine the best predictor of patient prognosis. Many sebaceous gland carcinomas and sweat gland carcinomas showed nuclear accumulation of p53, and patients with tumors showing a PCNA index (percentage of nuclei stained for PCNA) higher than 20%, and a p53 index (percentage of nuclei stained for p53) higher than 10% had short survival. Sebaceous gland carcinomas and sweat gland carcinomas showing c-erbB-2 expression had high PCNA (> 20%) and p53 (> 10%) indices, and were associated with poor prognosis. Histologically, sebaceous gland carcinomas showing a high degree of differentiation and severe nucleolar atypia had high PCNA and p53 indices. A growth pattern of small solid nests and strands, a low degree of differentiation, and the presence of lymphatic permeation in sweat gland carcinoma were often associated with high PCNA and p53 indices. These results suggest that nuclear accumulation of p53 plays an important role in the development of sebaceous gland carcinoma and sweat gland carcinoma. Assessment of PCNA and p53 indices together was very useful for prognostication of patient outcome, using cut-off values of 20% and 10%, respectively, to separate good prognosis from poor. Differentiation of sebaceous gland carcinoma, and c-erbB-2 expression by sweat gland carcinoma were significant independent prognostic indicators.

Adult↗

Glycerol regulates stratum corneum hydration in sebaceous gland deficient (asebia) mice.

The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences stratum corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) stratum corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control stratum corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal stratum corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized stratum corneum hydration, and the glycerol content of asebia stratum corneum was 85% lower than in normal stratum corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for stratum corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia stratum corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to stratum corneum hydration.

Animals↗

Effects of topically applied antiandrogenic compounds on sebaceous glands of hamster ears and flank organs.

Growth of sebaceous glands in the ears and flank organs of castrated male hamsters is dependent on androgen substitution. Taking this for granted, a study was done to compare the effects of topical antiandrogenic treatment in vivo on the morphology and size of sebaceous glands with the concomitant changes in in vitro metabolism of 3H-testosterone. The role of dihydrotestosterone in sebaceous gland stimulation was thereby investigated. Topical treatment was carried out with the androgen antagonist 17 alpha-propylmesterolone (PM), with 4-androsten-3-one-17 beta-carboxylic acid (17 beta-C), and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), both described as specific 4-steroid-5 alpha-reductase inhibitors, and with progesterone (PRO), which is an androgen receptor antagonist with 5 alpha-reductase inhibiting properties. Regrowth of sebaceous glands after castration and substitution with testosterone propionate or dihydrotestosterone could be inhibited by topical PM and PRO. This occurred irrespective of the influence on testosterone metabolism and irrespective of the mode of substitution. 4-MA, on the other hand, while exhibiting strong 5 alpha-reductase inhibition in vitro, was ineffective in reducing sebaceous gland sizes in vivo. The compound 17 beta-C was ineffective in every respect. In no case were systemic antiandrogenic effects on prostates and seminal vesicles observed. Our results support the view that the DHT formation rate has no regulatory function for growth of sebaceous glands in hamsters and that PM and PRO counteract the androgenic stimulus by their competitive antagonistic binding to the androgen receptor, but not by their influence on testosterone metabolism.

Administration, Topical↗

Hormonal control of hamster ear sebaceous gland lipogenesis.

The sites and hormonal control of lipogenesis in hamster ear sebaceous glands are reported. Sebaceous lipogenesis was determined in ear biopsies by incubation with glucose and tracer concentrations of 14C-acetate in buffer. The 14C-labeled lipids were saponified, extracted, and determined by liquid scintillation counting. Histologically, the ears contained many sebaceous glands. The glands of male animals were much larger and more heavily lipid-stained than glands from females. Lipogenesis was almost entirely confined to the sebaceous glands in the dermal stroma. Lipogenesis was considerably higher in ear biopsies from male hamsters than from female, castrate male, or hypophysectomized male hamsters. In contrast to published data using hypophysectomized rats, where dihydrotestosterone potently and testosterone only weakly increased sebum secretion, both testosterone and dihydrotestosterone potently increased lipogenesis in the ears of hypophysectomized male hamsters. Dihydrotestosterone was somewhat more potent than testosterone in the hamster. Hypophyseal hormones do not appear to be essential for androgen stimulated lipogenesis in the hamster. In female hamsters, 5 alpha-androstane-3 alpha, 17 beta-diol, testosterone, dihydrotestosterone, 4-androstene-3,17-dione, and 5 alpha-androstane-3,17-dione produced dose-dependent increases in lipogenesis. From this and other studies, it is suggested that androgens other than dihydrotestosterone could be physiologically important in man and animals in stimulating lipogenesis in sebaceous glands.

Androgens↗

Control of human sebocyte proliferation in vitro by testosterone and 5-alpha-dihydrotestosterone is dependent on the localization of the sebaceous glands.

Androgens stimulate the activity of sebaceous glands in vivo. In this study the in vitro effect of androgens on the proliferation of cultured human sebocytes derived from facial and non-facial skin were assessed. Human sebocytes from sebaceous glands isolated from the face and the upper and lower legs of five individuals were cultured in vitro with or without testosterone or 5-alpha-dihydrotestosterone (5 alpha-DHT) at different concentrations (10(-11)-10(-5) M). Cell proliferation was assessed in 96-well culture plates using a fluorometric assay. Testosterone and 5 alpha-DHT stimulated the proliferation of human facial sebocytes in a significant dose-dependent manner. In our system 5 alpha-DHT exhibited the strongest effect; on the contrary, the proliferation of non-facial sebocytes was inhibited by testosterone, whereas 5 alpha-DHT enhanced their growth. The stimulatory effect of 5 alpha-DHT was more prominent on facial than on non-facial sebocytes. These results provide first evidence that the effect of testosterone and 5 alpha-DHT on the proliferation of cultured human sebocytes may depend on the localization of the sebaceous glands at different skin regions.

Adult↗

Sebaceous gland hyperplasia on rabbit pinna induced by tetradecane.

To investigate the pathologic changes of sebaceous glands during comedo formation induced by topically applied substances in a rabbit pinna model, purified tetradecane was inuncted on the ventral aspect of the rabbit pinnas once a day for a week. Histologically, a marked hyperplasia of sebaceous glands, epidermis, and follicular epithelium was seen. These remarkably enlarged sebaceous glands were examined histochemically and ultrastructurally. The acinus size and cell population of the hyperplastic sebaceous gland were significantly increased over those of the normal sebaceous gland. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, normal distribution patterns of sulfhydryl (SH) and disulfide (SS) were seen in the peripheral to differentiating layers in the hyperplastic sebaceous glands. In the terminally differentiated layer, the brilliant SH fluorescence was gradually decreased and the SS fluorescence was gradually increased in intensity, indicating that most SH groups in the sebaceous cells were converted to SS linkages before holocrine secretion. By transmission electron microscopy, several cell layers of undifferentiated sebaceous cells were observed at the periphery of the large sebaceous gland. The differentiating sebaceous cells produced a large number of lipid droplets, which were produced in either rough or smooth endoplasmic reticulum. These cells were abruptly converted into homogeneously electron-dense cells which formed several layers. These homogeneous cells gradually lost their electron density before holocrine secretion. These findings indicate that the sebaceous cells in the hyperplastic sebaceous glands undergo a magnified step-by-step cell differentiation and play a role in slightly modified lipid formation, and that there may be an increased production of sebum in the rabbit pinna model. This is the first report of sebaceous hyperplasia induced by a topically applied substance on skin surface, except for androgens. The hyperplastic sebaceous glands could serve as a model for investigations of sebaceous cell differentiation and lipid formation.

Administration, Topical↗

Sebaceous gland activity in black skin.

Sebaceous gland secretion was measured in 649 male and female subjects, of whom 67 (10.3 per cent) were black. No consistent difference in sebaceous gland activity was found between black and white skin. As sebum is an integral etiologic factor in acne, these findings are consistent with the clinical impression and with epidemiologic data, albeit scant, that the incidence of acne vulgaris in the black population differs little, if at all, from the incidence in the white population.

Acne Vulgaris↗