性激素结合球蛋白在多囊卵巢综合征中的研究进展
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摘要
多囊卵巢综合征(PCOS)是女性常见的内分泌疾病,主要以排卵障碍,卵巢呈多囊样改变和高雄激素血症为特征。性激素结合球蛋白(SHBG)主要作用是结合睾酮和雌激素,调节性激素在血中的浓度。本文对SHBG基因表达水平与PCOS,SHBG水平和胰岛素抵抗(IR)、高雄激素血症、2型糖尿病、代谢综合征(MS)、妊娠糖尿病、乳腺癌和子宫内膜癌等远期并发症的相关性进行综述,以期为PCOS的诊断提供一定参考,为临床治疗提供指导。
Polycystic ovary syndrome(PCOS) is one of the most common endocrine disorders in female,and it is characterized by ovulation disorders,polycystic ovary and high androgen level.SHBG mainly binds to testosterone and estrogen to adjust the serum reproductive hormone levels.SHBG is a specific marker of PCOS.In this paper,the relationships between the expression level of SHBG and PCOS,insulin resistance(IR),hyperandrogenism and type II diabetes,metabolic syndrome(MS),gestational diabetes,long-term complications of breast cancer and endometrial cancer are reviewed,in order to provide a reference for diagnosis of PCOS and guidance of clinical treatment.
Polycystic ovary syndrome(PCOS) is one of the most common endocrine disorders in female,and it is characterized by ovulation disorders,polycystic ovary and high androgen level.SHBG mainly binds to testosterone and estrogen to adjust the serum reproductive hormone levels.SHBG is a specific marker of PCOS.In this paper,the relationships between the expression level of SHBG and PCOS,insulin resistance(IR),hyperandrogenism and type II diabetes,metabolic syndrome(MS),gestational diabetes,long-term complications of breast cancer and endometrial cancer are reviewed,in order to provide a reference for diagnosis of PCOS and guidance of clinical treatment.
引文
[1] Rosenfield RL.The Diagnosis of Polycystic Ovary Syndrome in Adolescents[J].Pediatrics,2015,136:1154-1165.
[2] Markatseli AE,Hatzi E,Pamporaki C,et al.Association of the(TAAAA)n repeat polymorphism of SHBG gene with the age at menopause in Greek postmenopausal women[J].Maturitas,2014,78:113-116.
[3] Kosova G,Urbanek M.Genetics of the polycystic ovary syndrome[J].Mol Cell Endocrinol,2013,373:29-38.
[4] Abu-Hijleh TM,Gammoh E,Al-Busaidi AS,et al.Common Variants in the Sex Hormone-Binding Globulin(SHBG)Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome[J].Ann Nutr Metab,2016,68:66-74.
[5] Ferk P,Teran N,Gersak K.The(TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome[J].Hum Reprod,2007,22:1031-1036.
[6]刘英,江霞.性激素结合球蛋白与胰岛素抵抗相关性疾病关系的研究进展[J].山东医药,2016,56:105-107.
[7] Pelanis R,Mellembakken JR,Sundstr9m-Poromaa I,et al.The prevalence of Type 2diabetes is not increased in normalweight women with PCOS[J].Hum Reprod,2017,32:2279-2286.
[8]郝晓园.性激素结合球蛋白在育龄期多囊卵巢综合征合并糖代谢异常患者血清中的表达及检测价值[J].现代中西医结合杂志,2017,26:172-173,174.
[9]牛静云,侯丽辉,寇丽辉,等.不同高雄激素血症表型多囊卵巢综合征患者临床特征分析[J].实用妇产科杂志,2018,34:286-290.
[10] Rosner W.Free estradiol and sex hormone-binding globulin[J].Steroids,2015,99(Pt A):113-116.
[11] Kupreeva Maria,Diane Abdoulaye,Lehner Richard,et al.Effect of Metformin and Flutamide on Insulin,Lipogenic and Androgen-Estrogen Signaling and Cardiometabolic Risk in a PCOS-prone Rodent Model[J].Am J Physiol Endocrinol Metab,2018.28,143-149.
[12] Livadas S,Kollias A,Panidis D,et al.Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome:evidence from 1345women with the syndrome[J].Eur J Endocrinol,2014,171:301-309.
[13] Wallace IR,McKinley MC,Bell PM,et al.Sex hormone binding globulin and insulin resistance[J].Clin Endocrinol(Oxf),2013,78:321-329.
[14] Jaschke N,Lunger F,Wildt L,et al.Beta endorphin in serum and follicular fluid of PCOS-and non-PCOS women[J].Arch Gynecol Obstet,2018,298:217-222.
[15] Thaler MA,Seifert-Klauss V,Luppa PB.The biomarker sex hormone-binding globulin-from established applications to emerging trends in clinical medicine[J].Best Pract Res Clin Endocrinol Metab,2015,29:749-760.
[16] Kim C,Halter JB.Endogenous sex hormones,metabolic syndrome,and diabetes in men and women[J].Curr Cardiol Rep,2014,16:467.
[17] Shin JY,Kim SK,Lee MY,et al.Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2diabetes[J].Diabetes Res Clin Pract,2011,94:156-162.
[18] Le TN,Nestler JE,Strauss JF,et al.Sex hormone-binding globulin and type 2diabetes mellitus[J].Trends Endocrinol Metab,2012,23:32-40.
[19] White MJ,Eren F,Agirbasli D,et al.SHBG gene polymorphism(rs1799941)associates with metabolic syndrome in children and adolescents[J].PLoS One,2015,10:e0116915.
[20] Muka T,Nano J,Jaspers L,et al.Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women:A Population-Based Cohort Study and Meta-analysis[J].Diabetes,2017,66:577-586.
[21] Fenske B,Kische H,Gross S,et al.Endogenous Androgens and Sex Hormone-Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes[J].J Clin Endocrinol Metab,2015,100:4595-4603.
[22] Hua X,Li M,Pan F,et al.Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients[J].Sci Rep,2017,7:14532.
[23] Siddiqui Khalid,Al-Rubeaan Khalid,Nawaz Shaik Sarfaraz,et al.Serum Sex Hormone Binding Globulin(SHBG)Relation with Different Components of Metabolic Syndrome in Men with Type 2Diabetes[J].Horm Metab Res,2018,50:138-144.
[24] Glueck CJ,Morrison JA,Daniels S,et al.Sex hormonebinding globulin,oligomenorrhea,polycystic ovary syndrome,and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24years[J].J Pediatr,2011,159:308-313.e2.
[25] Agirbasli M,Eren F,Agirbasli D,et al.Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort:lessons learned on LPL,CETP,LIPC,ABCA1,and SHBG[J].OMICS,2013,17:636-645.
[26] White MJ,Eren F,Agirbasli D,et al.SHBG gene polymorphism(rs1799941)associates with metabolic syndrome in children and adolescents[J].PLoS One,2015,10:e0116915.
[27]陈国芳,李春睿,范尧夫,等.短期极低热量饮食对代谢综合征患者代谢指标及性激素结合球蛋白的影响[J].中华糖尿病杂志,2016,8:410-413.
[28]钟卓慧.多囊卵巢综合征孕妇产科并发症及其危险因素分析[J].中国计划生育和妇产科,2017,9:9-12.
[29] Petry CJ,Ong KK,Hughes IA,et al.Early PregnancyAssociated Plasma Protein A Concentrations Are Associated With Third Trimester Insulin Sensitivity[J]. J Clin Endocrinol Metab,2017,102:2000-2008.
[30] Powe CE,Allard C,Battista MC,et al. Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus[J].Diabetes Care,2016,39:1052-1055.
[31] Hedderson MM,Xu F,Darbinian JA,et al.Prepregnancy SHBG concentrations and risk for subsequently developing gestational diabetes mellitus[J].Diabetes Care,2014,37:1296-1303.
[32]金镇,迟鑫姝,滕卫平,等.血糖控制满意的妊娠期糖尿病孕妇血清性激素结合球蛋白水平与妊娠结局的关系[J].中华妇产科杂志,2011,46:422-426.
[33] Maged AM,Moety GA,Mostafa WA,et al.Comparative study between different biomarkers for early prediction of gestational diabetes mellitus[J].J Matern Fetal Neonatal Med,2014,27:1108-1112.
[34] Johannsen TH,Main KM,Ljubicic ML,et al.Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development[J].J Clin Endocrinol Metab,2018,103:3028-3037.
[35] Coradini D,Orenti A,Venturelli E,et al.Serum levels of testosterone and SHBG in association with body mass index improve the predictive capability of consolidate tumor biomarkers in pre-and postmenopausal breast cancer patients[J].Jpn J Clin Oncol,2018,48:308-316.
[36]杨镒魟,周善杰,谷翊群.性激素结合球蛋白与某些生殖系统疾病的相关性[J].生殖医学杂志,2014,23:513-517.
[37] Fourkala EO,Blyuss O,Field H,et al. Sex hormone measurements using mass spectrometry and sensitive extraction radioimmunoassay and risk of estrogen receptor negative and positive breast cancer:Case control study in UK Collaborative Cancer Trial of Ovarian Cancer Screening(UKCTOCS)[J].Steroids,2016,110:62-69.
[38] Fung TT,Schulze MB,Hu FB,et al.A dietary pattern derived to correlate with estrogens and risk of postmenopausal breast cancer[J].Breast Cancer Res Treat,2012,132:1157-1162.
[2] Markatseli AE,Hatzi E,Pamporaki C,et al.Association of the(TAAAA)n repeat polymorphism of SHBG gene with the age at menopause in Greek postmenopausal women[J].Maturitas,2014,78:113-116.
[3] Kosova G,Urbanek M.Genetics of the polycystic ovary syndrome[J].Mol Cell Endocrinol,2013,373:29-38.
[4] Abu-Hijleh TM,Gammoh E,Al-Busaidi AS,et al.Common Variants in the Sex Hormone-Binding Globulin(SHBG)Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome[J].Ann Nutr Metab,2016,68:66-74.
[5] Ferk P,Teran N,Gersak K.The(TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome[J].Hum Reprod,2007,22:1031-1036.
[6]刘英,江霞.性激素结合球蛋白与胰岛素抵抗相关性疾病关系的研究进展[J].山东医药,2016,56:105-107.
[7] Pelanis R,Mellembakken JR,Sundstr9m-Poromaa I,et al.The prevalence of Type 2diabetes is not increased in normalweight women with PCOS[J].Hum Reprod,2017,32:2279-2286.
[8]郝晓园.性激素结合球蛋白在育龄期多囊卵巢综合征合并糖代谢异常患者血清中的表达及检测价值[J].现代中西医结合杂志,2017,26:172-173,174.
[9]牛静云,侯丽辉,寇丽辉,等.不同高雄激素血症表型多囊卵巢综合征患者临床特征分析[J].实用妇产科杂志,2018,34:286-290.
[10] Rosner W.Free estradiol and sex hormone-binding globulin[J].Steroids,2015,99(Pt A):113-116.
[11] Kupreeva Maria,Diane Abdoulaye,Lehner Richard,et al.Effect of Metformin and Flutamide on Insulin,Lipogenic and Androgen-Estrogen Signaling and Cardiometabolic Risk in a PCOS-prone Rodent Model[J].Am J Physiol Endocrinol Metab,2018.28,143-149.
[12] Livadas S,Kollias A,Panidis D,et al.Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome:evidence from 1345women with the syndrome[J].Eur J Endocrinol,2014,171:301-309.
[13] Wallace IR,McKinley MC,Bell PM,et al.Sex hormone binding globulin and insulin resistance[J].Clin Endocrinol(Oxf),2013,78:321-329.
[14] Jaschke N,Lunger F,Wildt L,et al.Beta endorphin in serum and follicular fluid of PCOS-and non-PCOS women[J].Arch Gynecol Obstet,2018,298:217-222.
[15] Thaler MA,Seifert-Klauss V,Luppa PB.The biomarker sex hormone-binding globulin-from established applications to emerging trends in clinical medicine[J].Best Pract Res Clin Endocrinol Metab,2015,29:749-760.
[16] Kim C,Halter JB.Endogenous sex hormones,metabolic syndrome,and diabetes in men and women[J].Curr Cardiol Rep,2014,16:467.
[17] Shin JY,Kim SK,Lee MY,et al.Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2diabetes[J].Diabetes Res Clin Pract,2011,94:156-162.
[18] Le TN,Nestler JE,Strauss JF,et al.Sex hormone-binding globulin and type 2diabetes mellitus[J].Trends Endocrinol Metab,2012,23:32-40.
[19] White MJ,Eren F,Agirbasli D,et al.SHBG gene polymorphism(rs1799941)associates with metabolic syndrome in children and adolescents[J].PLoS One,2015,10:e0116915.
[20] Muka T,Nano J,Jaspers L,et al.Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women:A Population-Based Cohort Study and Meta-analysis[J].Diabetes,2017,66:577-586.
[21] Fenske B,Kische H,Gross S,et al.Endogenous Androgens and Sex Hormone-Binding Globulin in Women and Risk of Metabolic Syndrome and Type 2 Diabetes[J].J Clin Endocrinol Metab,2015,100:4595-4603.
[22] Hua X,Li M,Pan F,et al.Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients[J].Sci Rep,2017,7:14532.
[23] Siddiqui Khalid,Al-Rubeaan Khalid,Nawaz Shaik Sarfaraz,et al.Serum Sex Hormone Binding Globulin(SHBG)Relation with Different Components of Metabolic Syndrome in Men with Type 2Diabetes[J].Horm Metab Res,2018,50:138-144.
[24] Glueck CJ,Morrison JA,Daniels S,et al.Sex hormonebinding globulin,oligomenorrhea,polycystic ovary syndrome,and childhood insulin at age 14 years predict metabolic syndrome and class III obesity at age 24years[J].J Pediatr,2011,159:308-313.e2.
[25] Agirbasli M,Eren F,Agirbasli D,et al.Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort:lessons learned on LPL,CETP,LIPC,ABCA1,and SHBG[J].OMICS,2013,17:636-645.
[26] White MJ,Eren F,Agirbasli D,et al.SHBG gene polymorphism(rs1799941)associates with metabolic syndrome in children and adolescents[J].PLoS One,2015,10:e0116915.
[27]陈国芳,李春睿,范尧夫,等.短期极低热量饮食对代谢综合征患者代谢指标及性激素结合球蛋白的影响[J].中华糖尿病杂志,2016,8:410-413.
[28]钟卓慧.多囊卵巢综合征孕妇产科并发症及其危险因素分析[J].中国计划生育和妇产科,2017,9:9-12.
[29] Petry CJ,Ong KK,Hughes IA,et al.Early PregnancyAssociated Plasma Protein A Concentrations Are Associated With Third Trimester Insulin Sensitivity[J]. J Clin Endocrinol Metab,2017,102:2000-2008.
[30] Powe CE,Allard C,Battista MC,et al. Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus[J].Diabetes Care,2016,39:1052-1055.
[31] Hedderson MM,Xu F,Darbinian JA,et al.Prepregnancy SHBG concentrations and risk for subsequently developing gestational diabetes mellitus[J].Diabetes Care,2014,37:1296-1303.
[32]金镇,迟鑫姝,滕卫平,等.血糖控制满意的妊娠期糖尿病孕妇血清性激素结合球蛋白水平与妊娠结局的关系[J].中华妇产科杂志,2011,46:422-426.
[33] Maged AM,Moety GA,Mostafa WA,et al.Comparative study between different biomarkers for early prediction of gestational diabetes mellitus[J].J Matern Fetal Neonatal Med,2014,27:1108-1112.
[34] Johannsen TH,Main KM,Ljubicic ML,et al.Sex Differences in Reproductive Hormones During Mini-Puberty in Infants With Normal and Disordered Sex Development[J].J Clin Endocrinol Metab,2018,103:3028-3037.
[35] Coradini D,Orenti A,Venturelli E,et al.Serum levels of testosterone and SHBG in association with body mass index improve the predictive capability of consolidate tumor biomarkers in pre-and postmenopausal breast cancer patients[J].Jpn J Clin Oncol,2018,48:308-316.
[36]杨镒魟,周善杰,谷翊群.性激素结合球蛋白与某些生殖系统疾病的相关性[J].生殖医学杂志,2014,23:513-517.
[37] Fourkala EO,Blyuss O,Field H,et al. Sex hormone measurements using mass spectrometry and sensitive extraction radioimmunoassay and risk of estrogen receptor negative and positive breast cancer:Case control study in UK Collaborative Cancer Trial of Ovarian Cancer Screening(UKCTOCS)[J].Steroids,2016,110:62-69.
[38] Fung TT,Schulze MB,Hu FB,et al.A dietary pattern derived to correlate with estrogens and risk of postmenopausal breast cancer[J].Breast Cancer Res Treat,2012,132:1157-1162.
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