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.     

Age-related changes in sebaceous gland activity.

The sebaceous glands of man show age-related differences in their activity as determined by quantitative and qualitative examination of sebum. Sebaceous secretion is low in children and begins to increase in mid- to late childhood under the influence of androgens. This rise continues until the late teens, after which no further significant change takes place until late in life. In elderly men, sebum levels remain essentially unchanged from those of younger adults until the age of 80. In women, sebaceous secretion decreases gradually after menopause and shows no significant change after the 7th decade. The most likely explanation for the decrease in sebaceous gland secretion with age in both men and women is a concomitant decrease in the endogenous production of androgens. Although surface lipid levels fall with age, paradoxically the sebaceous glands become larger, rather than smaller, as a result of decreased cellular turnover. Nonetheless, as the higher surface lipid levels after administration of fluoxymesterone (a synthetic testosterone derivative) indicate, the glands have the capacity to respond to androgens.     

Chronological ageing and photoageing of the human sebaceous gland

The human sebaceous gland undergoes both extrinsic and intrinsic ageing. The latter is associated with morphological changes and alteration in the sebaceous gland activity. The high androgen-dependent sebum secretion in neonates falls during childhood, starts to rise again during puberty and reaches its maximum in young adults. While the number of sebaceous glands remains the same during life, sebum levels tend to decrease after menopause in females, whereas no major changes appear until the eighth decade of life in men. Reduced androgen levels in aged individuals lead to a slow cellular turnover in the sebaceous glands resulting in hyperplasia of the facial sebaceous glands in advanced age. Ultraviolet radiation and immune suppression (cyclosporin A with corticosteroids) represent cofactors for the development of sebaceous gland hyperplasia. Current molecular findings indicate that overexpression of the ageing-associated gene Smad7 and parathormone-related protein correlate with sebaceous gland hyperplasia, whereas c-myc overexpression is associated with enhanced sebum production. On the other hand, down-regulation of the mismatch repair genes hMLH-1 and hMSH-2 may promote the development of sebaceous gland carcinoma. In addition to spontaneous single tumours, sebaceous gland carcinomas have been reported in immune-suppressed transplant recipients (azathiorpine, cisplatin, cyclosporin A) and in association with the Muir-Torre syndrome. Microsatellite instability with a loss of the mismatch repair gene hMSH-2 has been detected in immune suppressed patients and under photo-induced DNA damage. Topical and systemic oestrogens offer treatment options for skin xerosis in menopausal females. A combination of isotretinoin and interferon-alpha may prevent tumour development in patients with Muir-Torre syndrome.     

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

We have reported recently that inactivation of the essential autophagy‐related gene 7 (Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, (Atg7 ΔKC), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP‐LC3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 ΔKC mice compared to those of controls (Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age‐matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids (FFA) and cholesterol, and a 5‐fold increase in the proportion of fatty acid methyl esters (FAME). In addition, the most common diester wax species (58‐60 carbon atoms) were increased, while shorter species (54‐55 carbon atoms) were under‐represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.     

The effect of topically applied gamma-Oryzanol on sebaceous glands.

The action of topically applied γ-Oryzanol (triterpineol ester with ferulic acid) on the sebaceous glands was investigated using the double blind method. 1% γ-Oryzanol ointment, and the ointment base as control, were applied symmetrically to the backs of rats in the same hair cycle stage. The turnover time of sebaceous gland cells was examined by quantitating ⁸H-thymidine incorporation and colchicine-arrested mitosis. The labeling index and arrested mitosis values were significantly elevated by the topical application of γ-Oryzanol. Elevation of these values was paralleled by an increase in sebum production (reported in a previous paper) (4), showing that sebaceous gland cells are stimulated by γ-Oryzanol. Other than sex hormones, γ-Oryzanol is the only substance known to stimulate sebaceous glands by topical application.     

Epidermal growth factor receptor and the sebaceous gland

Side effects of EGFR inhibition do not include primary sebaceous gland changes. Dahlhoff et al. evaluated EGFR actions on the sebaceous glands in mutant mice with constitutively activated EGFR expression. Enlarged, hyperproliferative sebaceous glands and increased sebum levels were detected, and c‐myc levels were increased. These data indicate that EGFR‐induced sebocyte mechanisms are probably species‐specific. The detected SCD deregulation is compatible with previous reports, whereas SCD is a marker of sebaceous differentiation, and its expression is essential for lipogenesis. As SCD expression is upregulated by TLR2 activation, there is a link between SCD overexpression and sebaceous differentiation/lipogenesis with inflammation.     

Two cases of genital neutrophilic sebaceous adenitis

Sebaceous glands without a follicular structure are present in the eyelid margin (meibomian glands), lip, glans penis and vulva. Inflammatory disease of a sebaceous gland lacking follicles is rare, except for meibomitis. We report the first two cases of vulval sebaceous adenitis. Painful, yellowish‐orange papules/nodules recurred at the vulval mucocutaneous junction or mucosa during the luteal phase of the menstrual cycle. Histopathologically, a dense neutrophilic infiltration was observed within the sebaceous ducts. In both cases, oral minocycline improved the condition. They had been treated with antiherpetic agents. It is possible that women diagnosed with recurrent genital herpes have genital neutrophilic sebaceous adenitis.     

Risk factors for sebaceous gland diseases and their relationship to gastrointestinal dysfunction in Han adolescents

Sebaceous gland diseases are a group of common dermatological diseases with multiple causes. To date, a systematic report of the risk factors for sebaceous gland diseases in adolescents has not been published. The aim of this study was to assess the prevalence and risk factors for certain sebaceous gland diseases (seborrhea, seborrheic dermatitis, acne, androgenetic alopecia and rosacea) and their relationship to gastrointestinal dysfunction in adolescents. From August-October, 2002-2005, a questionnaire survey was carried out to obtain epidemiological data about sebaceous gland diseases. Using random cluster sampling, 13 215 Han adolescents aged 12-20 years were recruited from four countries or districts (Macau; Guangzhou, China; Malaysia; and Indonesia). The statistical software SPSS ver. 13.0 was used to analyze the data. The prevalence of seborrhea, seborrheic dermatitis, acne, androgenetic alopecia and rosacea was 28.27%, 10.17%, 51.03%, 1.65% and 0.97%, respectively. Based on multivariate logistic regression analysis, the risk factors for sebaceous gland diseases included: age; duration of local residency; halitosis; gastric reflux; abdominal bloating; constipation; sweet food; spicy food; family history of acne; late night sleeping on a daily basis; excessive axillary, body and facial hair; excessive periareolar hair; and anxiety. There was a statistically significant difference in the prevalence of gastrointestinal symptoms (halitosis; gastric reflux; abdominal bloating; constipation) between patients with and without sebaceous gland diseases (chi(2) = 150.743; P = 0.000). Gastrointestinal dysfunction is an important risk factor for diseases of the sebaceous glands and is correlated with their occurrence and development.     

Die Talgdrüse

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 a target organ but also an important formation site of hormones, and especially of active androgens. Hormonal activity is based on an hormone (ligand)-receptor interaction, whereas sebocytes express a wide spectrum of hormone receptors. 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. Atopic dermatitis, seborrheic dermatitis, psoriasis and acne vulgaris are some of the disease on which pathogenesis and severity sebaceous lipids may or are surely involved.     

Steroid hormone receptors and their relevance for sebum production in the sebaceous gland ear model of the Syrian hamster

We determined the capacity of steroid hormone receptors in the sebaceous glands of intact nontreated, castrated, with testosterone substituted castrated male, intact female, and intact with testosterone substituted female animals using the animal ear model of the Syrian hamster. The steroid hormone binding capacity was compared with the sebaceous gland areas and sebogenesis. Intact male animals showed large sebaceous follicles, a high sebogenesis rate, and high capacity for sexual hormone binding proteins. In castrated males, the sebaceous gland areas and sebogenesis were both diminished, and androgen and estrogen receptors were decreased. When the castrated males were substituted with testosterone propionate, the sebaceous glands showed large volumes, high sebum production, and androgen binding activity again. In female animals having small sebaceous follicles and a low rate of sebogenesis, testosterone propionate enlarged the sebaceous glands and increased sebogenesis and the capacity of androgen binding. One can conclude from these data that testosterone is not only the main hormone for sebum production but also induces the synthesis of its own receptor.     

皮脂腺痣皮肤镜及反射式共聚焦显微镜特征分析

【摘要】 目的 探讨不同年龄患者皮脂腺痣的皮肤镜及反射式共聚焦显微镜特征。方法 2016年1 - 12月将武汉市第一医院皮肤科门诊经组织病理学确诊的83例皮脂腺痣患者,按年龄分成4组,采集、分析其皮肤镜及反射式共聚焦显微镜图像特征。结果 < 10岁组21 例,皮损在皮肤镜下表现为橘色背景下独立分布、较为一致的黄红色、球块状结构,似鹅卵石样排列,伴血管增生、扩张;反射式共聚焦显微镜下可见皮脂腺发育不全, 仅见幼稚毛囊。10 ~ 20岁组28例,皮肤镜下可见聚集分布、与毛囊无关、大小不同的黄色圆形、卵圆形结构,伴毛细血管扩张;反射式共聚焦显微镜下可见,真表皮交界处及真皮浅层葡萄串样皮脂腺结构,中央为管状/柄样结构,外周为簇集分布、鱼籽/蛙卵样增生的皮脂腺小叶,其上方表皮往往呈疣状/乳头瘤样增生。21 ~ 59岁组30例,影像学表现同10 ~ 20岁组。≥ 60岁组4例,影像学特征主要为乳头瘤样增生。结论 皮脂腺痣是一种动态发展的疾病,不同年龄阶段影像学表现不尽相同;在皮肤镜及反射式共聚焦显微镜下均具有特征性结构,可作为有效的无创性诊断方法。     

Effects of skin extract on sebaceous gland function in the rat

Summary The subcutaneous injection of a rat skin extract inhibits sebum excretion. The mitotic rate in the sebaceous glands is reduced. Therefore, a chalone of the sebaceous gland seems to exist. The regulation of sebum excretion is discussed.     

Influence of photoperiodism on testicular function and sebaceous glands in Syrian hamster

The photoperiod (i.e., the daylight fraction of the 24-h day and its seasonal changes) influences the annual cycle of many mammalian species. Especially the Syrian hamster (Mesocricetus auratus), which is an appropriate animal model to investigate the sebaceous gland activity, shows a strong photoperiodism controlling the sexual development as well as the function of androgen-controlled organs such as sebaceous glands. Short photoperiods with accompanying long dark periods lead to a sexual regression while long photoperiods stimulate the recrudescence. In light-physiologic studies Syrian hamsters were exposed to different light schedules. The daily light exposure was increased from 8 to 12, 13, 14, and 16 h. Sebaceous gland areas, weight of testes and accessory glands, tubular areas, and plasma levels of testosterone were determined. Syrian hamsters are sexually stimulated at a daily light exposure of 14 h. Below this light threshold the sexual regression begins. At a light schedule of 8 h the testes shrink, plasma testosterone levels and sebaceous gland areas show a significant reduction ("photoperiodic castration"). Therefore, in experiments of androgen-controlled organs of the Syrian hamster a minimum daily light period of 14 or 16 h is necessary for a sufficient testicular function and therefore for an effective stimulation of the sebaceous gland activity. Control animals of the same age and the same light schedule should be required to avoid pitfalls of photoperiodic effects.     

Photodynamic therapy of facial nevus sebaceous

A 29‐year‐old man visited our department with an orange‐colored patch on his right cheek. A skin biopsy confirmed the diagnosis of nevus sebaceous. As surgical excision was considered too destructive, photodynamic therapy (PDT) was proposed. Sixteen sessions of PDT was performed in total. There was a definitive but transient decrease in sebum production and destruction of the sebaceous glands. Overall, we were not able to achieve long‐lasting clinical improvement after PDT.     

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.     

Doxorubicin-induced alopecia is associated with sebaceous gland degeneration

Alopecia, accompanied by skin dryness, is one of the distressing side effects often occurring in chemotherapy-treated cancer patients. Little is known of the effects of chemotherapy on sebaceous glands, despite their importance in hair follicle homeostasis. This study investigates sebaceous gland morphology and the response of SZ95 sebaceous gland cell line to doxorubicin (DXR) treatment. The morphology of sebaceous glands during intraperitoneal DXR treatment was investigated by optical and electron microscopy in a 7-day-old rat model and further confirmed in an adult mouse model. Moreover, in vitro studies using the SZ95 sebaceous gland cell line were performed to assess the response of sebocytes to DXR in terms of cell proliferation, apoptosis, and necrosis. DXR treatment induced sebaceous gland regression and occasionally caused their complete disappearance. This observed damage and disappearance preceded DXR-induced hair loss. In vitro experiments using the SZ95 sebaceous gland cell line indicated that DXR treatment induced a differentiation process leading to premature sebocytes apoptosis. Owing to the importance of the sebaceous gland in hair follicle homeostasis, DXR-induced involution of this gland might be related to subsequent hair loss.     

Sebum excretion rates in mothers and neonates

As neonates have a high sebum production compared with 6-month-old babies, we wished to investigate the relationship of sebum production in mother and neonate. The sebum excretion rate (SER) was therefore measured in 10 mothers prenatally, and in each mother and baby as soon after birth as possible, and again 5-12 weeks postnatally. There was a significant correlation between the maternal and neonatal SER perinatally. The perinatal SER in the babies was markedly higher than the postnatal sample. These observations suggest an important role for the maternal hormonal environment on the infant sebaceous glands. There is animal evidence which suggests that the endocrine environment of the neonate influences the sebaceous gland development in puberty, but it is not known whether babies with a high SER are more prone to seborrhoea and acne in later life.     

On the mechanism of sebaceous secretion

Summary Following the studies of Kligman, most investigators now believe that sebaceous glands function continuously in excreting sebum to the skin surface [7, 8]. Populations of differentiating cells are maintained by mitotic activity both in the peripheral cells of the sebaceous lobules and in aggregations of undifferentiated cells which extend through the body of the lobules. Once formed, and as long as maintained by circulating hormones, each lobule continues to produce a stream of differentiating cells which accumulate sebum as they move towards the sebaceous duct and finally disrupt to release their contents into the pilosebaceous canal.After intradermal injections of ³H-thymidine to label germinative cells during DNA replication, up to 28 days elapse before all labeled cells disappear from the glands. When differentiating cells are labeled with ³H-amino acids, much of the label is lost in 7 days. Likewise, when lipids are labeled with ¹⁴C-acetate, the average excretion time for the labeled sebum is 8 days. To this time may be added the renewal time of undifferentiated cells to give an average sebaceous cell transition time of 14 days [15].From knowledge of the time between synthesis and excretion of sebum, sebum production rates were calculated from the sebum content of punch biopsies. The transit time of sebum in the follicular canals was estimated to be 14 h. Production rates determined in this way agree with those measured by long-term absorption of sebum at the skin surface.This study was supported in part by a grant from the US Public Health Service (AM 22083)     

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.