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      Papel dos Androgênios Adrenais e Periféricos na Modulação dos Níveis da Globulina Ligadora dos Hormônios Sexuais na Pubarca Precoce Translated title: Role of Adrenal and Peripheral Androgens in Modulating SHBG Levels in Premature Pubarche

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          Abstract

          Avaliamos em 26 meninas com pubarca precoce (PP) e 14 controles (7,3±1,0 x 7,0±2,0 anos) os efeitos dos androgênios adrenais e periféricos na modulação dos níveis da globulina ligadora dos hormônios sexuais (SHBG) na infância. Foram avaliados: a idade óssea (IO) e o índice de massa corporal (IMC) e os níveis de androstenediona (A), testosterona (T), dehidro-epiandrostenediona e seu sulfato (DHEA e SDHEA), dihidrotestosterona (DHT), 3a-androstanediol glucuronídeo (3a-diolG) e SHBG. A IO (8,0±1,4 x 8,3±1,4 anos) foi semelhante, mas o IMC (18,7±3,1 x 16,7±2,0, p=0,03) foi maior na PP. O SDHEA (0,7±0,4 x 0,3±0,2µg/mL, p<0,001) foi maior, o 3a-diolG (1,1±0,7x 0,6±0,6ng/mL) e a DHT (180±95 x 132±68pg/mL) tenderam a ser maiores; o SHBG (60±24 x 89± 26nmol/L, p=0,001) foi menor; e a DHEA (4,8±2,6 x 3,3±2,0ng/mL), T (133±149 x 90±59pg/mL) e A (603±330 x 420±318pg/mL) foram semelhantes. A SHBG se correlacionou negativamente com o IMC (r= -0,53; p<0,001), DHT (r= -0,43, p=0,005) e 3a-diolG (r= -0,46, p=0,02), mas no modelo de regressão múltipla, a SHBG se correlacionou somente com o IMC e o 3a-diolG. Esses dados sugerem que os níveis elevados do SDHEA resultam do aumento da secreção dos androgênios adrenais, enquanto o 3a-diolG e a DHT podem refletir a maior conversão periférica dos androgênios na PP. Além disso, tanto o peso corporal e o 3a-diolG, mas não a T e os androgênios adrenais, parecem ser importantes reguladores da SHBG na infância.

          Translated abstract

          We investigated in 26 girls with premature pubarche (PP) and 14 age-matched controls (7.3±1.0 x 7.0±2.0 years) the role of adrenal and peripheral androgens in the regulation of sex hormone-binding globulin (SHBG) during childhood. Bone age (BA) and body mass index (BMI) were determined, together with androstenedione (A), testosterone (T), dehydroepiandrosterone and its sulfate (DHEA and DHEAS), dihydrotestosterone (DHT), 3a-androstanediol glucuronide (3a-diolG) and SHBG. Although BA was similar (8.0±1.4 x 8.3±1.4 years), BMI was higher in PP (18.7±3.1 x 16.7±2.0, p=0.03). Plasma levels of DHEAS (0.7±0.4 x 0.3±0.2µg/mL, p<0.001), 3a-diolG (1.1±0.7 x 0.6±0.6ng/mL, p=0.06) and DHT (180±95 x 132±68pg/mL, p=0.09) were greater, whereas SHBG (60±24 x 89±26nmol/L, p=0.001) was lower; and levels of DHEA (4.8±2.6 x 3.3±2.0ng/mL), T (133±149 x 90±59pg/mL) and A (603±330 x 420±318pg/mL) were similar. SHBG was negatively correlated with BMI (r= -0.53, p< 0.001), DHT (r= -0.43, p=0.005) and 3a-diolG (r= -0.46, p=0.02), but in the multiple regression model, SHBG correlated only with BMI and 3a-diolG. These findings suggest that increased levels of SDHEA result from a greater secretion of adrenal androgens, whereas 3a-diolG and DHT may reflect a greater skin utilization of androgens in the PP. Moreover, both body weight and 3a-diolG, but not T and adrenal androgens, could be important regulators of SHBG during childhood.

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          Most cited references26

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          Synthesis and regulation of sex hormone-binding globulin in obesity.

          A Hautanen (2000)
          Sex hormone-binding globulin (SHBG) is a plasma glycoprotein with high binding affinity for testosterone and dihydrotestosterone and lower affinity for estradiol. SHBG is synthesized in the liver, and its plasma level is important in the regulation of plasma free and albumin-bound androgens and estrogens. Obesity and particularly excess visceral fat, known risk factors for cardiovascular and metabolic diseases, are associated with decreased testosterone levels in males and SHBG levels in both sexes. SHBG is usually positively correlated with high-density lipoprotein cholesterol and negatively correlated with triglyceride and insulin concentrations. A positive association between SHBG and various measures of insulin sensitivity has been demonstrated in both sexes, suggesting that decreased SHBG levels may be one of the components of the metabolic syndrome. We have examined pituitary-adrenocortical function, glucose tolerance, and lipoprotein and hormone levels in a large cohort of Finnish males. Abdominal obesity appears to be associated with slight hypocortisolemia and increased sensitivity to exogenous adrenocorticotropin stimulation, which may contribute to the hyperinsulinemia and related metabolic changes including decreased SHBG levels in males.
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            Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche.

            The fasting insulin resistance index, mean blood glucose, mean serum insulin (MSI), early insulin response to glucose, glucose uptake rate in peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were evaluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postmenarcheal (B5; n = 16)] and in 86 Tanner stage- and bone age-matched controls. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Body mass indexes did not differ significantly between patients and controls within the same pubertal stage. MSI levels showed a significant increase with pubertal onset in all subjects, as expected. Patients showed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, respectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake rate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respectively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01, P < 0.05, and P < 0.001, respectively) compared to controls. Among others, significant correlations between SHBG and MSI levels (r = -0.49; P < 0.0001) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were found in all subjects. Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend strong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The possible causal role of hyperinsulinemia in adrenal and/or ovarian androgen hypersecretion remains to be established.
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              Normal and Almost Normal Precocious Variations in Pubertal Development Premature Pubarche and Premature Thelarche Revisited

              Premature pubarche, premature thelarche and complete precocious puberty are usually simply normal phenomena occurring at an early age. This is not necessarily the case, however, and they may sometimes be harbingers of reproductive endocrine disturbances in adulthood. Consequently, girls with these complaints cannot be entirely reassured that they are of no consequence, and they should be followed to ascertain whether pubertal reproductive function is eventually normal.
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                Author and article information

                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo, SP, Brazil )
                1677-9487
                October 2002
                : 46
                : 5
                : 520-525
                Affiliations
                [01] Rio de Janeiro RJ orgnameUniversidade do Estado do Rio de Janeiro orgdiv1Faculdade de Ciências Médicas orgdiv2Hospital Universitário Pedro Ernesto
                Article
                S0004-27302002000500005 S0004-2730(02)04600505
                3dd3a2cc-846f-4b3e-ae64-9e74f4e7f053

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

                History
                : 16 May 2002
                : 10 June 2002
                : 08 March 2002
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 26, Pages: 6
                Product

                SciELO Brazil

                Categories
                Artigos Originais

                Pubarca Precoce,SHBG,Androgens,Premature Pubarche,Androgênios

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