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PubMed2006

Gender differences and effects of sex steroids and dehydroepiandrosterone on androgen and oestrogen alpha receptors in mouse sebaceous glands.

BACKGROUND: It is generally believed that the sebaceous gland is an intracrine organ which synthesizes its own active hormones to meet its local needs. OBJECTIVES: To understand further the mechanisms of sex steroid action in mouse sebaceous glands. METHODS: We have used immunocytochemistry to examine the expression of oestrogen receptor alpha (ERalpha) and androgen receptor (AR) in mouse sebaceous glands. RESULTS: In intact males AR is exclusively localized in the nuclei of basal and mature sebocytes, while in females it is present at a lower level in both the nuclei and the cytoplasm. Three weeks following gonadectomy (GDX), a marked decrease of AR labelling is observed in male sebocytes, while no change occurs in female sebocytes. Treatment of GDX animals with dihydrotestosterone (DHT) or dehydroepiandrosterone (DHEA) increases AR expression, while 17beta-estradiol (E2) decreases the stimulatory effect of DHT and DHEA. ERalpha is detected only in basal sebocytes of intact females but not in males. Following treatment with E2, ERalpha expression becomes visible in GDX males while DHT and DHEA inhibit the effect of E2. CONCLUSIONS: The present data show gender differences and demonstrate that DHT, E2 and DHEA exert specific effects on the expression of AR and ERalpha in mouse sebocytes.

Animals↗
PubMed1977

The effect of various treatments on the size of sebaceous glands of hairless mice and hairless hamsters.

The effect of castration on the size of sebaceous glands of male hairless mice and male hairless hamsters was studied over a period of 4 weeks. Statistically significant decreases in the size of sebaceous glands were observed. The effects of intracutaneous injections of micronized crystalline suspensions of testosterone, testosterone propionate, testosterone phenylpropionate, testosterone decanoate and nandrolone phenylpropionate on the sebaceous glands of castrated hairless mice, castrated hairless hamsters and intact female hairless hamsters were studied over a period of one week. Highly significant increases in sebaceous gland volume were observed 6-7 days after treatment. The effects of subcutaneous and intracutaneous injections of micronized crystalline suspensions of testosterone on the sebaceous glands of intact male and female hairless hamsters were examined at sites local and distal to the injection. Increases in sebaceous gland volume were limited to local sites in the male but increases were observed locally and distally in the female. There was no difference between subcutaneous and intracutaneous injections.

Animals↗
PubMed1999

Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95).

Human facial sebaceous gland cells were transfected with a PBR-322-based plasmid containing the coding region for the Simian virus-40 large T antigen. The resulting proliferating cell cultures have been passaged over 50 times to date, have been cloned, and show no signs of senescence after 4&DF;1 2 y in vitro, whereas normal human sebocytes can only be grown for three to six passages. The immortalized transfected cells, termed SZ95, expressed the Simian virus-40 large T antigen and presented an hyper-diploid-aneuploid karyotype with a modal chromosome number of 64.5. The SZ95 cell line exhibited epithelial, polymorphous characteristics with different cell sizes of up to 3.25-fold during proliferation and 6-fold at confluence, showing numerous cytoplasmic lipid droplets. The cells showed large cytoplasm profiles with abundant organelles, including vacuoles and myelin figures which indicated lipid synthesis. Lack of or only few desmosomal areas were observed. SZ95 cells expressed molecules typically associated with human sebocytes, such as keratins 7, 13, and 19, and several proteins of the polymorphous epithelial mucin family. Functional studies revealed synthesis of the sebaceous lipids squalene and wax esters as well as of triglycerides and free fatty acids, even after 25-40 passages; active lipid secretion; population doubling times of 52.4 +/- 1.6 h; reduced growth but maintenance of lipid synthesis under serum-free conditions; and retrieval of cell proliferation after addition of 5alpha-dihydrotestosterone. Retinoids significantly inhibited proliferation of certain SZ95 cell clones in the expected magnitude 13-cis-retinoic acid > all-trans-retinoic acid > > acitretin. Thus SZ95 is an immortalized human sebaceous gland cell line that shows the morphologic, phenotypic and functional characteristics of normal human sebocytes.

Antigens, Polyomavirus Transforming↗
PubMed1995

Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin.

The presence of 5 alpha-reductase (5 alpha-R) in skin may indicate that the androgen regulation of sebaceous glands and sebum production requires the local conversion of testosterone to dihydrotestosterone. The goals of this study were to identify which isozyme of 5 alpha-R (type 1 or type 2) is expressed in sebaceous glands from facial areas, scalp, and non-acne-prone areas; to determine if 5 alpha-R activity is concentrated in sebaceous glands; to assess whether there are regional differences in this enzyme's activity; and to test the effects of azasteroid inhibitors and 13-cis retinoic acid on 5 alpha-R in these tissues. Sebaceous glands were microdissected from facial skin, scalp, and non-acne-prone skin (arm, breast, abdomen, leg), and the activity of 5 alpha-R was determined. A total of 49 samples from 23 male and 21 female subjects without acne (age range, 16 to 81 years, 56 +/- 20 years [mean +/- SD]) was analyzed. The biochemical properties of the enzyme in each of the samples tested are consistent with those of the type 1 5 alpha-R. Minimal to no type 2 5 alpha-R was detected. The level of 5 alpha-R activity was significantly higher in the sebaceous glands compared to whole skin in facial skin (p = 0.047), scalp (p = 0.039), and non-acne-prone skin (p = 0.04). Enzyme activity in sebaceous glands from facial skin and scalp was significantly higher than in a comparable amount of sebaceous gland material obtained from non-acne-prone areas (32 +/- 6 [mean +/- SEM]), 35 +/- 7 (mean +/- SEM) versus 6.0 +/- 3.0 (mean +/- SEM) pmol/min/mg protein, p = 0.014 and 0.007, respectively). Finasteride and 13-cis retinoic acid were poor inhibitors of the enzyme with 50% inhibitory concentration values greater than 500 nM. These data demonstrate that in the skin from older patients without acne the type 1 isozyme of 5 alpha-R predominates, its activity is concentrated in sebaceous glands and is significantly higher in sebaceous glands from the face and scalp compared to non-acne-prone areas, and the action of 13-cis retinoic acid in the control of acne is not at the level of 5 alpha-R. Furthermore, we suggest that specific inhibition of the type 1 5 alpha-R may offer a viable approach to the management of sebum production and, hence, acne.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

[A case of giant sebaceous gland carcinoma without adequate treatment].

BACKGROUND: A patient with a sebaceous gland carcinoma without adequate treatment is reported. CASE: A 67-year-old man underwent an operation on his left upper eyelid after a diagnosis of chalazion in 1981. Two years after the initial operation, he noticed a tumor in the left upper eyelid. In 1987, he visited another hospital and was diagnosed with sebaceous gland carcinoma by a tissue biopsy. He left it untreated against medical advice. When he visited our hospital in 1996, the tumor was as large as 80 x 75 x 40 mm and the left upper and lower eyelids stuck together. After admission, he died of myocardial infarction 23 days after his visit to our hospital. Autopsy revealed that the tumor had extended into the orbital cavity, paranasal sinus, and base of the skull, with metastasis to the preauricular, submandibular, and cervical lymph nodes and both lungs. The pathology of the tumor was a moderately differentiated sebaceous gland carcinoma. CONCLUSION: This case showed the natural course of extension and metastasis of a sebaceous gland carcinoma.

Aged↗
PubMed1999

Laser hair removal affects sebaceous glands and sebum excretion: a pilot study.

BACKGROUND: During laser-assisted hair removal, sebaceous glands closely associated with hair follicles might also be affected. OBJECTIVE: We investigated the effect of the long-pulsed ruby laser on sebaceous glands. METHODS: Sebum excretion rates (SERs) of 16 subjects were measured quantitatively by means of sebum-absorbent tape and analyzed by means of image analysis techniques on laser-treated sites, compared with adjacent untreated areas. Evaluation was done at an average of 9 months (range, 4.5 to 12 months) after the last treatment. Histologic examinations were performed on 3 representative subjects before treatment, immediately after treatment, and 9 months after the last treatment. RESULTS: Significant increases in SERs were observed in 11 of 16 subjects (68.75%). Three subjects (18.75%) showed lower SERs, whereas 2 subjects (12.5%) demonstrated no difference in SERs between treated and untreated areas. Biopsy specimens showed an apparent reduction in sebaceous gland size. Specimens taken immediately after laser irradiation revealed sporadic damage to sebaceous glands. CONCLUSION: In some patients a variable but statistically significant increase in sebum excretion occurs 4 to 12 months after ruby-laser hair removal treatment at high fluences. A reduction in sebaceous gland sizes on laser-treated areas was observed. We hypothesize that decreased resistance to sebum outflow may explain this result, following miniaturization or absence of hair shaft after ruby laser treatment. Further study is needed to assess mechanisms for this interesting response.

Adult↗
PubMed2003

Hedgehog signaling regulates sebaceous gland development.

Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous gland development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were functional, secreting their contents directly onto the skin's surface instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.

Animals↗
PubMed1991

[Morphological changes in sebaceous glands with aging in human males].

Using a computer stereographic analysis, the normal human forehead skin from 16 males of ages ranging from 7 to 77 years were investigated to known the morphological changes of the sebaceous glands with aging. The volume of sebaceous glands increased abruptly in teens, reaching maximum in the 20s; it was maintained at high levels even at middle ages and then began to decrease gradually in the 60s. The volume of sebaceous glands positively correlated with the number of the sebaceous cells but not with their sizes. Ultrastructually, in the large sebaceous glands, and peripheral cells were cuboidal, whereas they were flat in the small sebaceous glands. It is concluded that the sebaceous glands in males show no morphological change in relation to age between the 20s and 50s.

Adolescent↗
PubMed1980

Influence of cyproterone acetate and estradiol on cell kinetics in the sebaceous gland of the golden hamster ear.

The cell kinetics of the sebaceous gland of the hamster ear were analysed in untreated animals, in animals treated with cyproterone acetate, and in animals treated with estradiol. Both active substances lead to a reduction in the size of the sebaceous gland (measurement with the integration plate), to a reduction of mitoses (colcemide method), to a reduction in the 3H-thymidine labelling index, to a prolongation of the S-phase (double labelling technique with 3H- and 14C-thymidine), and to a decrease in the number of cells labelled with 3H-thymidine which remain in contact with the basal lamina of the sebaceous gland 6 days after application of the isotope. The results indicate that, like cyproterone acetate, estradiol reduces the effect of androgens on cell kinetics in the sebaceous gland under the test conditions chosen, even if in an entirely different way.

Androgen Antagonists↗
PubMed2002

Loss of fragile histidine triad (FHIT) expression and microsatellite instability in periocular sebaceous gland carcinoma in patients with Muir-Torre syndrome.

PURPOSE: To report fragile histidine triad expression and microsatellite instability in periocular sebaceous gland carcinoma. DESIGN: Interventional case series. METHODS: Biopsy specimens of periocular sebaceous gland carcinoma obtained from six patients (mean age, 60 +/- 17 years; range, 38 to 83 years, 5 male, 1 female) with Muir-Torre syndrome and histopathologically proven sebaceous gland carcinoma were studied immunohistochemically for the presence of fragile histidine triad protein. Polymerase chain reaction-based analysis of the markers BAT25, BAT26, D2S123, D5S346, and D17S250 was performed for microsatellite instability in tumorous and matching normal tissues. RESULTS: Fragile histidine triad protein was detectable in the sebaceous gland carcinoma from one patient with microsatellite instability. It was not detectable in sebaceous gland carcinoma specimens from five patients without any evidence of microsatellite instability. CONCLUSION: Inactivation of fragile histidine triad tumor suppressor gene or inactivation of the mismatch-repair system resulting in microsatellite instability may contribute to the development of periocular sebaceous gland carcinoma in Muir-Torre syndrome.

Acid Anhydride Hydrolases↗
PubMed1996

Adrenal steroid precursors exert potent androgenic action in the hamster sebaceous glands of flank organs and ears.

To assess the effect of the androgen precursors dehydroepiandrosterone (DHEA) and androstenedione (4-ene-dione) on androgen-sensitive parameters in the skin of the hamster, these two steroids were released from SILASTIC implants inserted sc into castrated male hamsters. The pigmented area of the flank organs, the size of the underlying sebaceous glands, [3H]thymidine incorporation into these sebaceous glands, and the size of the ear sebaceous glands were measured. The decrease in flank organ size caused by orchidectomy was partially reversed by DHEA and completely reversed by 4-ene-dione, testosterone (T), or dihydrotestosterone (DHT) implants. Similarly, the size of the sebaceous glands of the flank organs was reduced 88.1% by castration, whereas DHEA, 4-ene-dione, T, and DHT implants reversed the effect of orchidectomy. Orchidectomy also decreased the sizes of the sebaceous glands of the ears; DHEA, 4-ene-dione, T, and DHT implants increased their sizes to 50.6%, 81.9%, 91.6%, and 105.8% of the values found in intact hamsters, respectively. Parallel results were observed on the labeling of flank organ sebaceous glands with [3H]thymidine as well as on prostate weight. Serum concentrations of T and DHT became undetectable in castrated hamsters and were increased to intact or slightly elevated values in animals receiving implants of DHEA, 4-ene-dione, or T. The present results show that DHEA and 4-ene-dione are potent stimulators of androgen-sensitive parameters in the sebaceous glands of both the flank organs and ears in the hamster and illustrate the importance of extragonadal or peripheral intracrine formation of active steroids. It is suggested that the castrated hamster supplemented with adrenal precursor steroids is a good model that can closely mimic the human situation, where adrenal steroids play an important role in androgen formation and action in peripheral tissues.

Androgens↗
PubMed1997

Importance of sebaceous glands in cutaneous penetration of an antiandrogen: target effect of liposomes.

The significance of the sebaceous gland pathway in the cutaneous permeation of an antiandrogen, 4-[3-(4-hydroxybutyl)-4,4-dimethyl -2,5-dioxo-1-imidazolidinyl]-2-(trifluoromethyl)benzonitrile (RU 58841), was studied with normal hairless rat skin and an induced scar hairless rat skin without sebaceous glands. RU 58841 was dissolved in an alcoholic solution and encapsulated in liposomes for comparison. After 24 h, the cumulative percentage of RU 58841 absorbed in vitro was 3-4-fold higher in the normal skin than in the scar skin; in the case of liposomes, the accumulation of the drug in the normal dermis was significantly higher than in the scar one. In the in vivo cutaneous distribution, the epidermis and dermis of the normal skin contained higher amounts of RU 58841 than the scar skin (ninefold with the solution and 16-fold with liposomes). An autoradiography study showed that with the solution, the drug was mainly localized in the stratum corneum/epidermis, and with the liposomes, the drug was mainly localized in the sebaceous glands. We concluded that the sebaceous glands constituted the main pathway for RU 58841. The alcoholic solution encouraged the localization of the drug into the stratum corneum, whereas liposomes targeted the sebaceous glands.

Androgen Antagonists↗
PubMed2006

Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne.

BACKGROUND: The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex-hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown. OBJECTIVE: We hypothesized that transcription factors involved in sex formation and regulation of steroidogenesis in the classical steroidogenic organs are also expressed in the sebaceous glands. Their possible role in the pathogenesis of acne were investigated. METHODS: We used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting to analyse the expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in cultured human sebocytes and the facial skin of acne patients. RESULTS: The in situ hybridization study showed SOX-9 mRNA mainly localized in basal keratinocytes, the basal layer of the sebaceous glands and eccrine glands. Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1 and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be higher in the acne-prone male patients, while DAX-1 was stronger in subjects without acne, although both were statistically insignificant. CONCLUSION: Our findings confirm the expression of some sex-determining genes in human sebaceous glands. Further studies on a larger patient population including the normal controls are needed to elucidate the functional significance of these transcription factors in the pathogenesis of acne.

Acne Vulgaris↗
PubMed2002

Selective photothermolysis of the sebaceous glands for acne treatment.

BACKGROUND AND OBJECTIVES: The purpose of this study is to evaluate the efficacy of a long pulse diode laser (Cynosure, Inc.) to target and destroy enlarged sebaceous glands that are preloaded with Indocyanine green (ICG) chromophore. STUDY DESIGN/MATERIALS AND METHODS: This study was designed in three phases. First, preliminary studies were performed to determine the ability of ICG to penetrate into enlarged sebaceous glands. Once penetration of the sebaceous gland was confirmed, the second phase was to determine the necessary parameters for the diode laser to effectively target the ICG loaded glands. This was done using laser-tissue interaction analysis. The final phase was done with patients that had active acne on their back to determine if selective destruction of the sebaceous glands could be achieved and also to assess the safety and efficacy of this novel treatment for acne. RESULTS: Fluorescence microscopy of biopsy samples show evidence of ICG penetration into the sebaceous glands. Histological examination of biopsy samples from the treated areas finds selective necrosis of the sebaceous glands. Preliminary clinical results demonstrate a decrease in acne noted in the treatment area at 3, 6, and 10 months follow-up. CONCLUSIONS: ICG and diode laser treatment is a new approach for the treatment of acne based on experimentally observed selective photothermolysis of the sebaceous glands.

Acne Vulgaris↗