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Acne: hormonal concepts and therapy.

Acne vulgaris is the most common skin condition observed in the medical community. Although we know that hormones are important in the development of acne, many questions remain unanswered regarding the mechanisms by which hormones exert their effects. Androgens such as dihydrotestosterone (DHT) and testosterone, the adrenal precursor dehydroepiandrosterone sulfate (DHEAS), estrogens such as estradiol, and other hormones, including growth hormone and insulin-like growth factors (IGFs), may be important in acne. It is not known whether these hormones are taken up from the serum by the sebaceous gland, whether they are produced locally within the gland, or whether a combination of these processes is involved. Finally, the cellular and molecular mechanisms by which these hormones exert their influence on the sebaceous gland have not been fully elucidated. Hormonal therapy is an option in women with acne not responding to conventional treatment or with signs of endocrine abnormalities.

Acne Vulgaris↗

Histological characteristics of the pelage skin of rough fur mice (C3H/HeJ- ruf/ruf).

Pelage skin of C3H/HeJ mice homozygous at an autosomal recessive mutant locus, rough fur (ruf) which is located on chromosome 9, was histologically analyzed. Sebaceous glands synthesizing lipids were larger in the mutant mice than in controls in an examination by Sudan IV staining. Electron microscopic analysis of the sebaceous gland showed that lipid droplets were denser in mutant mice than in control mice, and that they were irregular in shape in ruf mice while those of controls were round. Our results suggested that rough fur (ruf) mice might be an animal model for hyperlipogenesis of the pelage skin.

Animals↗

[Treatment of acne with antiandrogens--an evidence-based review].

BACKGROUND: Increased sebaceous gland activity with seborrhea is one of the major pathogenetic factors in acne. Antiandrogen treatment targets the androgen-metabolizing follicular keratinocytes and the sebaceous gland leading to sebostasis, with a reduction of the sebum secretion rate of 12.5-65%. Antiandrogens can be classified based on their mechanism of action as androgen receptor blockers, inhibitors of circulating androgens by affecting ovarian function (oral contraceptives), inhibitors of circulating androgens by affecting the pituitary (gonadotropin-releasing hormone agonists and dopamine agonists in hyperprolactinemia), inhibitors of adrenal function, and inhibitors of peripheral androgen metabolism (5alpha-reductase inhibitors, inhibitors of other enzymes). METHODS: All original and review publications on antiandrogen treatment of acne as monotherapy or in combination included in the MedLine system were extracted by using the terms "acne", "seborrhea", "polycystic ovary syndrome", "hyperandrog", and "treatment" and classified according to their level of evidence. RESULTS: The combinations of cyproterone acetate (2 mg)/ethinyl estradiol (35 microg), drospirenone (3 mg)/ethinyl estradiol (30 microg), and desogestrel (25 microg)/ ethinyl estradiol (40 microg) for 1 week followed by desogestrel (125 microg)/ethinyl estradiol (30 microg) for 2 weeks showed the strongest anti-acne activity. Gestagens or estrogens as monotherapy, spironolactone, flutamide, gonadotropin-releasing hormone agonists, and inhibitors of peripheral androgen metabolism cannot be endorsed based on current knowledge. Low dose prednisolone is only effective in late-onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. Treatment with antiandrogens should only be considered if none of the contraindications exist. CONCLUSION: Antiandrogen treatment should be limited to female patients with additional signs of peripheral hyperandrogenism or hyperandrogenemia. In addition, women with late-onset or recalcitrant acne who also desire contraception can be treated with antiandrogens as can those being treated with systemic isotretinoin. Antiandrogen treatment is not appropriate primary monotherapy for noninflammatory and mild inflammatory acne.

Acne Vulgaris↗

Fel d I levels in cat anal glands.

BACKGROUND: Major cat allergen Fel d I is produced consistently by skin and by sebaceous glands before being spread on the fur. OBJECTIVE: Since cats have tubular anal glands secreting sebum, proteins and lipids, we looked at the possible presence of Fel d I in these secretions and compared the levels found to those already reported in other cat tissues or secretions. METHODS: Thirty-seven cats were studied. Fel d I dosage in the anal sacs' secretions was performed using an enzyme linked immunosorbent assay (ELISA) method and total protein evaluation by the Bradford's method. RESULTS: The geometric mean Fel d I concentration was 41 U/g secretion which represents 3.4% of the total protein levels. This amount is the highest ever reported in cat tissues or secretions. CONCLUSION: The close association of Fel d I protein with skin sebaceous glands and anal sacs both with holocrine function and lipids' secretions in one hand, and the homology of chain I of Fel d I with some steroid-binding proteins in other hand, suggest a possible physiological role for Fel d I in the regulation of lipids on skin and cat fur.

Allergens↗

A case of multiple sebaceous epithelioma: analysis of microsatellite instability.

Sebaceous gland tumor is a rare disease that is a sign of Muir-Torre syndrome, an autosomal, dominantly inherited genodermatosis characterized by the presence of at least one sebaceous gland tumor and a minimum of one internal malignancy. Recent studies have indicated that defective DNA mismatch repair occurs in Muir-Torre syndrome. Cutaneous lesions may occur before diagnosis of the internal cancer. We describe a 64-year-old male patient with multiple sebaceous epitheliomas with no evident internal malignancy. Microsatellite instability, determined by examining dinucleotide CA repeats at the microsatellite loci, was observed in DNA from one sebaceous epithelioma but not from the other two sebaceous epitheliomas or from one basal cell epithelioma with sebaceous differentiation, suggesting that this condition is unlikely to be due to germ-line mutation of mismatch repair genes.

Adenocarcinoma, Sebaceous↗

Jugulo-sternal-gland tumors in male tree shrews (Tupaia belangeri).

Adenocarcinomas of the jugulo-sternal glands were observed in seven adult male tree shrews (Tupaia belangeri) at biopsy or necrospy. Five of these tumors were classified as carcinomas of the sebaceous gland compartment; one was diagnosed as a papilliform adenoma of apocrine (monoptychic) sweat glands; and one was of a mixed sebaceous gland/apocrine sweat gland structure. Four sebaceous gland carcinomas had histologic evidence of vascular invasion; one had metastasized to the regional lymph nodes and lungs and had also invaded the thoracic muscles.

Adenocarcinoma↗

Further observations on spontaneous neoplasms in the Mongolian gerbil, Meriones unguiculatus.

One hundred sixty Mongolian gerbils, Meriones unguiculatus, were examined for the presence of naturally occurring lesions. The first recognized cases of cecal adenocarcinoma, testicular teratoma, and sebaceous gland pad carcinoma were found. Neoplasms previously reported from the gerbil and also seen in the present study included ovarian theca lutein and granulosa lutein cell tumors, sebaceous gland pad adenoma, cutaneous squamous cell carcinoma, malignant melanoma, and renal and splenic hemangiomas. Calcinosis cutis was also observed in two male gerbils.

Adenocarcinoma, Mucinous↗

A more reliable photometric technique for the measurement of scalp sebum excretion.

The objective assessment of antiseborrhoeic therapy for the scalp requires a reliable technique for the measurement of sebaceous gland activity. Previously published methods were tried but found to be unreliable. This paper describes a photometric technique which gave repeatable results and demonstrated a reduction of sebaceous gland activity on the scalp with both oral isotretinoin and topical II alpha-hydroxyprogesterone. The accuracy of the method was achieved by careful preparation of the scalp but was affected by recent shampooing.

Adult↗

Skin lipids: an update.

The stratum corneum lipids, responsible for the epidermal water barrier, consist principally of ceramides, cholesterol, cholesteryl sulfate, and free fatty acids. These lipids are arranged in multiple intercellular lamellae that provide an efficient water barrier because of the crystalline array of the straight and predominantly saturated lipid chains. Interlamellar linkages provided by lipids based on 30-carbon omega-hydroxyacids may be responsible for holding together the intercellular lamellae as well as for assembly of the lamellar granules of the granular cells. The normally ordered exfoliation of corneocytes as they arrive at the surface seems to require hydrolysis of the cholesteryl sulfate to free cholesterol. The sebaceous glands secrete continuously, producing sebum that consists predominantly of triglycerides, wax esters, and squalene. High rates of sebum production per sebocyte result in low levels of linoleate in the sebaceous esters, subjecting the follicular epithelium to essential fatty acid deficiency and the characteristic hyperkeratosis that results in comedo formation. Suppression of sebum production by drugs elevates sebum linoleate concentration and relieves follicular hyperkeratosis. Thus, sebum continues to be a prime suspect in the crime of acne. Low levels of sebaceous gland activity are not correlated with the occurrence of dry skin.

Acne Vulgaris↗

The pilosebaceous unit is part of the skin immune system.

It is well established that the functional state of sebaceous glands in vivo is a tightly regulated process orchestrated through the interaction of male sex hormones and functional androgen receptors expressed on sebocytes. In the last few years, however, it has become increasingly apparent that sebocytes like epidermal keratinocytes express a variety of cytokines which are implicated in inflammatory and immune responses. For example, sebocytes in vivo have been found to highly express tumor necrosis factor alpha (TNF-alpha) as determined by immunohistochemical and electron-microscopic methods. Moreover, certain neuropeptides including vascular intestinal peptide and proopiomelanocortin (POMC) peptides as well as their receptors have been localized within the pilosebaceous unit of murine and human skin. Since POMC peptides such as alpha-melanocyte-stimulating hormone have recently been shown to exert important immunoregulatory effects by antagonizing the function of proinflammatory cytokines (e.g interleukin 1, interleukin 6 and TNF-alpha), induction of immunosuppressive cytokines (like interleukin 10), modulation of costimulatory molecule expression (e.g. B7-2) or suppression of macrophage-derived nitric oxide, complex interactions between these mediators and their target cells within the pilosebaceous gland seem to exist. The successful cultivation of sebocytes will provide a model by which the effect of these mediators can be studied in detail in order to shed light onto the various pathophysiological conditions of sebaceous glands.

Animals↗

Topical minoxidil does not act as an antiandrogen in the flank organ of the golden Syrian hamster.

Little is known about the mechanism of action of minoxidil-induced hair growth in male pattern baldness. We studied the potential antiandrogenic effect of topical minoxidil administered at the same dose and in the same vehicle that has been used successfully clinically in human subjects on the androgen-dependent cutaneous structures of the flank organ of the golden Syrian hamster. Minoxidil applied topically to one flank organ had no androgenic effect. Neither 1% nor 5% minoxidil topically applied for three weeks prevented the androgen-dependent growth of the pigmented spot, the sebaceous gland, or the hair follicle diameter induced by subcutaneous Silastic capsules filled with crystalline testosterone. As a positive control in the same experiments, 5% progesterone did significantly inhibit pigment and sebaceous gland enlargement. We conclude that there is no antiandrogenic component to the mechanism of action of topical minoxidil in the hamster flank organ, and thus there is probably no antiandrogenic role in man either.

Androgen Antagonists↗

Skin appendage involvement in anal intraepithelial neoplasia.

BACKGROUND: High-grade anal intraepithelial neoplasia (AIN III) may be premalignant. Surgical excision of large areas of anal epithelium carries significant morbidity. Ablation treatments may carry less morbidity; however, the depth of ablation is uncertain and failure to ablate dysplasia in hair shafts and other skin appendages may lead to early recurrence. METHODS: This study assesses morphometric aspects of skin appendages in perianal skin and anal canal mucosa in tissues from 30 patients with AIN III. Both normal and dysplastic epithelium was assessed in each patient. The depth to which AIN III involved skin appendages was measured using computerized image analysis. RESULTS: Both the perianal epidermis and anal canal mucosa affected by AIN III were significantly thicker than normal. Nineteen of 30 patients with AIN III had skin appendage involvement. Some 57 per cent of hair follicles (79 of 138), 16 per cent of sebaceous glands (11 of 69) and 25 per cent of sweat glands (24 of 96) observed beneath an abnormal epithelium had evidence of AIN. The median depth of AIN involvement of the hair follicle was 1.14 (range 0.44-1.67) mm, sebaceous glands 1.44 (range 0.96-1.90) mm, and sweat glands 0.94 (range 0.50-2.20) mm. These figures do not take into account tissue shrinkage due to histological processing. CONCLUSION: AIN III involvement of epithelial appendages is a significant problem. For disease eradication, tissue destruction or removal to a depth of at least 2.2 mm below the adjacent basement membrane is required. Surgical excision of high-grade AIN remains the treatment of choice.

Adult↗

Effect of oestradiol-17 beta on perineal and neck skin glands in heifer calves.

Ten 16-week-old Friesian x Hereford heifer calves were split into experimental and control groups. Experimental animals were given an implant of oestradiol-17 beta in the ear whilst controls were given blank implants. They were killed 14 days later. After implantation the experimental group had consistently greater (P less than 0.01) plasma concentrations of oestradiol-17 beta than the control group. After death, sebaceous gland volume in the perineal region was greater (P less than 0.01) in the experimental than in the control group, whereas sebaceous gland volume in the neck was smaller (P less than 0.01). Sweat gland volume in the perineal region was greater (P less than 0.01) in the experimental than in the control group. There was no difference between groups in the volume of sweat glands in the neck.

Animals↗

The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues.

The expression of the neu oncogene product was investigated in invasive and non-invasive ductal carcinomas of the breast, non-neoplastic lesions of the breast, fragments of normal adult and fetal breasts and in several other normal and fetal tissues at different weeks of pregnancy by means of an immunohistochemical study with monoclonal antibodies. The staining pattern along the cytoplasmic membrane was specific for malignancy and occurred in 29% of the breast carcinomas. It was observed in invasive carcinomas as well as in ductal carcinoma in situ and it showed a significantly higher expression in premenopausal women than in postmenopausal women. This higher expression was also present in oestrogen receptor-negative tumours. The tubules of the fetal and adult kidney, the absorption cells of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult skin, the adult endocervix, the endometrium, the C-cells of the thyroid, hepatocytes and all ductal cells of the fetal breast showed a constant diffuse intracytoplasmic granular staining. staining. The same granular intracytoplasmic staining pattern was focally observed in rare cases of normal breast tissue in adults and in some cases of epitheliosis, aprocrine metaplasia and some breast carcinoma cells, which did not express neu oncogene product on their membrane. Western blot experiments showed that the cytoplasmic protein had a molecular weight of 155 kD (kilodaltons); the membrane protein is the known 185 kD neu protein.

Adult↗

Chloracne, "the hallmark of dioxin intoxication".

Clinical experiences and laboratory studies are described involving a population of workers who were exposed in a plant making 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), including a trichlorophenol runaway reaction. Workers were followed for a period of four years, and 30 years later a mortality analysis was done on those exposed to runaway reaction material to determine possible increased risks for causes of death. Subsequently, a morbidity study on 436 employees involving three cohorts was carried out to determine the long-term health effects associated with the production of 2,4,5-T including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The mortality and morbidity studies demonstrated that the standardized mortality ratio for all causes of death was 69, and for cancer at all sites and cardiovascular disease it was 100 and 68, respectively. The most significant observations emerging from the morbidity study were that 86% of the exposed persons developed chloracne at some time and that 52.7% still had chloracne on examination 20 to 30 years after the initial exposure. There appeared to be no evidence, on a long-term basis, of increased risks for cardiovascular disease, hepatic disease, renal disease, central and peripheral nerve problems, reproductive problems, or birth defects among the exposed and those who had chloracne among the exposed. Studies on the cell kinetics and pathogenesis of chloracne indicate that TCDD induces the modulation of undifferentiated sebaceous gland cells to keratinocytes. This action results in a disappearance of sebaceous glands and substitution of closed comedones and keratin cysts. Production workers have the highest frequency and severity of chloracne and systemic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acne Vulgaris↗

Esterification of (4--14C)cholesterol by cutaneous bacteria (Staphylococcus epidermidis, Propionibacterium acnes, and Propionibacterium granulosum).

Cholesterol and cholesteryl esters constitute 3 to 5% of the lipids derived from human sebaceous glands. The present study demonstrates that cutaneous bacteria, Staphylococcus epidermidis, and to a lesser extent Propionibacterium acnes, and Propionibacterium granulosum, esterify [4--14C]cholesterol to steryl esters in vitro. The degree of esterification is a characteristic of the strain of organism, ranging from 0 to 32.7% in the organisms tested. Cholesterol esterification in these experiments was dependent on the addition of homogenates of isolated, pooled sebaceous glands to the incubation medium. Indirect evidence suggests that the fatty acids from sebaceous triglycerides are utilized for cholesterol esterification by the bacteria. These results indicate that the proportion of steryl esters in skin surface lipids may be influenced by the density of the microbial population in the skin.

Carbon Radioisotopes↗

Morphology and histogenesis of anal region and clitoral gland tumors induced in mice by 1,2-dimethylhydrazine.

Ninety-seven tumors induced in the anal region in female CBA and BALB/c mice by 1,2-dimethylhydrazine were examined histologically. Tumors originated mainly from the following sources: epidermis (papillomas and basal cell neoplasms), pilosebaceous complexes of the anal region (keratoacanthomas, cystic squamous cell tumors, and adenomas of the perianal sebaceous glands), and clitoral (preputial) glands (adenomas and adenoacanthomas). A subcutaneous location and late ulceration were characteristics of many tumors originating from the pilosebaceous complexes and clitoral glads. From 31 to 43% of all anal tumors were of sebaceous gland (perianal or clitoral) origin. Cystic squamous cell tumors were morphologically similar to type II keratoacanthomas of rodents. Squamous cell tumors of any origin finally became squamous carcinomas.

Adenocarcinoma↗

Expression of cutaneous fatty acid-binding protein and its mRNA in rat skin.

Cutaneous fatty acid-binding protein (C-FABP) has been purified from rat skin. Since there was little information about the role of C-FABP in the skin, we investigated the expression of C-FABP and its mRNA in normal rat skin using an immunohistochemical technique and in situ hybridization. In the epidermis, C-FABP mRNA was found to be expressed in basal cells and highly in prickle cells, while C-FABP itself was strongly expressed in the upper prickle and the granular cell layers. In sebaceous glands, both C-FABP and its mRNA were expressed in both peripheral and differentiating cells, although the expression of C-FABP mRNA gradually reduced during differentiation of sebocytes. Since epidermis and sebaceous glands are active sites of fatty acid synthesis, these results suggest that C-FABP may have important roles in the transport and synthesis of fatty acids.

Animals↗