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      Hiperplasia sebácea cutânea: estudo piloto para a correlação da doença com hormônios androgênios Translated title: Sebaceous hyperplasia: a pilot study to correlate this skin disease with circulating androgen levels

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          Abstract

          FUNDAMENTOS: As glândulas sebáceas são suscetíveis à ação dos hormônios androgênios e apresentam proliferação benigna com a idade, ou seja, hiperplasia. OBJETIVOS: Estudo piloto para verificar se há correlação entre a taxa de hormônios masculinos circulantes e o aumento da incidência da hiperplasia das glândulas sebáceas. MÉTODOS: 16 pacientes do sexo feminino, com diagnóstico de hiperplasia sebácea cutânea, foram comparados a um grupo-controle de mesmo gênero e idades semelhantes, sem a doença. Ambos os grupos foram submetidos a testes de dosagem sanguínea para avaliação das taxas de hormônios androgênios circulantes (testosterona livre e total, androstenediona). Os resultados foram tabulados e analisados estatisticamente. RESULTADOS: Os dados demonstraram não haver mudanças nos níveis de hormônios masculinos circulantes dos pacientes com hiperplasia sebácea cutânea, quando comparados ao grupo-controle. CONCLUSÃO: Os dados sugerem que não há alterações estatisticamente significantes nas taxas dos hormônios circulantes (testosterona livre e total, androstenediona, deidroepiandrosterona, sulfato de deidroepiandrosterona) dos pacientes com hiperplasia sebácea cutânea.

          Translated abstract

          BACKGROUND: The sebaceous glands are susceptible to the effects of androgens. A benign proliferation of these hormones, i.e. hyperplasia, occurs with age. OBJECTIVES: This was a pilot study to demonstrate whether any correlation exists between circulating androgen levels and an increase in the incidence of sebaceous hyperplasia. METHODS: Sixteen female patients with a diagnosis of sebaceous hyperplasia were compared to a control group of females of a similar age without the disease. Blood tests were performed on participants of both groups to measure circulating androgen levels (free and total testosterone and androstenedione levels). Results were tabulated for statistical analysis. RESULTS: These data showed no statistically significant differences in circulating androgen levels between the patients with sebaceous hyperplasia and the control group. CONCLUSION: These data suggest that no significant changes occur in circulating androgen levels [free and total testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate] in patients with sebaceous hyperplasia.

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          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.
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            The Human Sebocyte Culture Model Provides New Insights into Development and Management of Seborrhoea and Acne

            Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin 1α expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5α-reductase and metabolized testosterone to androstenedione, 5α-androstanedione, 5α-dihydrotestosterone, androsterone and 5α-androstanediol, whereas the levels of 5α-reductase activity were probably not feedback regulated. 4,7β-Dimethyl-4-aza-5αcholestan-3-one, a type 1 5α-reductase inhibitor, induced an early, marked down-regulation of 5α-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 10 3 -fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.
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              The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity.

              To evaluate the androgen control of sebum, subjects with complete androgen insensitivity and male pseudohermaphrodites with inherited 5 alpha-reductase deficiency and decreased dihydrotestosterone (DHT) production had sebum production studied. A hydrophobic polymeric film applied to the forehead was used to measure sebum production through the use of air filled micropores. Sebum scores of normal preadrenarchal children (ages 2-6), and normal age-matched adult males and females, were studied as well as males treated with the 5 alpha-reductase inhibitor, finasteride, for benign prostatic hyperplasia who were studied at baseline and after drug therapy. Androgen insensitive subjects had no sebum production by this methodology, and the results were identical to preadrenarchal children. In contrast, adult male pseudohermaphrodites with 5 alpha-reductase deficiency and a selective decrease in DHT production had sebum production scores identical to normal age-matched males. Males with benign prostatic hyperplasia treated with the 5 alpha-reductase inhibitor, finasteride, to lower DHT levels did not decrease the sebum score from baseline values. The lack of demonstrable sebum in androgen-insensitive subjects clearly demonstrates the absolute androgen control of sebum production. The DHT dependency of the sebaceous gland, however, could not be demonstrated in this study. Two 5 alpha-reductase isoenzymes 1 and 2, have been described. 5 alpha-reductase-2 is the gene responsible for inherited 5 alpha-reductase deficiency. Although the degree of inhibition of DHT in utero and in adulthood in male pseudohermaphrodites with a defect in 5 alpha-reductase-2 enzyme activity caused severe impairment of external genital and prostate differentiation and decreased facial and body hair, it had no demonstrable effect on sebaceous gland development or function. Furthermore, lowering DHT levels in adulthood had no effect on sebum production. If the gland is rich in the enzyme 5 alpha-reductase-2, it is proposed that the sebaceous gland is either exquisitely sensitive to DHT, requiring only small amounts for normal development and function, or that male levels of testosterone compensate for DHT and maintain normal sebaceous gland activity throughout life. It is also possible that 5 alpha-reductase-1 is the enzyme of the sebaceous gland and is unaffected in the inherited condition and by finasteride.
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                Author and article information

                Journal
                abd
                Anais Brasileiros de Dermatologia
                An. Bras. Dermatol.
                Sociedade Brasileira de Dermatologia (Rio de Janeiro, RJ, Brazil )
                0365-0596
                1806-4841
                October 2011
                : 86
                : 5
                : 917-923
                Affiliations
                [01] São Paulo SP orgnameUniversidade Federal de São Paulo orgdiv1Departamento de Dermatologia Brasil
                Article
                S0365-05962011000500009 S0365-0596(11)08600509
                31ec15eb-e843-4ff1-b52a-e0e02468530e

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 20 May 2010
                : 09 July 2011
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 30, Pages: 7
                Categories
                Investigação

                Glândulas sebáceas,Hormônios, substitutos de hormônios e antagonistas de hormônios,Hormônios,Hiperplasia,Sebaceous glands,Hyperplasia,Hormones, hormone substitutes, and hormone antagonists,Hormones

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