Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men

被引：29

作者：

Huhtaniemi, Ilpo T. ^{[1
]}

Pye, Stephen R. ^{[2
]}

Holliday, Kate L. ^{[2
]}

Thomson, Wendy ^{[2
]}

O'Neill, Terence W. ^{[2
]}

Platt, Hazel ^{[3
]}

Payne, Debbie ^{[3
]}

John, Sally L. ^{[2
]}

Jiang, Min ^{[4
]}

Bartfai, Gyoergy ^{[5
]}

Boonen, Steven ^{[6
,7
]}

Casanueva, Felipe F. ^{[8
]}

Finn, Joseph D. ^{[2
]}

Forti, Gianni ^{[9
]}

Giwercman, Aleksander ^{[10
]}

Han, Thang S. ^{[11
]}

Kula, Krzysztof ^{[12
]}

Lean, Michael E. J. ^{[13
]}

Pendleton, Neil ^{[14
]}

Punab, Margus ^{[15
]}

Silman, Alan J. ^{[2
]}

Vanderschueren, Dirk ^{[7
,16
]}

Labrie, Fernand ^{[17
]}

Wu, Frederick C. W. ^{[18
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England

[2] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res Campaign Epidemiol Unit, Manchester M13 9PT, Lancs, England

[3] Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Integrated Genom Med Res, Manchester M13 9PT, Lancs, England

[4] Univ Turku, Dept Physiol, FIN-20520 Turku, Finland

[5] Albert Szent Gyorgyi Med Univ, Dept Obstet Gynaecol & Androl, H-6725 Szeged, Hungary

[6] Katholieke Univ Leuven, Leuven Univ Div Geriatr Med, B-3000 Louvain, Belgium

[7] Katholieke Univ Leuven, Ctr Metab Bone Dis, B-3000 Louvain, Belgium

[8] Univ Santiago de Compostela, Dept Med, Complejo Hosp Univ Santiago, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, E-15780 Santiago De Compostela, Spain

[9] Univ Florence, Androl Unit, Dept Clin Physiopathol, I-50139 Florence, Italy

[10] Lund Univ, Reprod Med Ctr, Malmo Univ Hosp, S-20502 Malmo, Sweden

[11] Royal Free Hosp, Sch Med, Royal Free & Univ Coll Hosp, Dept Endocrinol, London NW3 2PF, England

[12] Med Univ Lodz, Dept Androl & Reprod Endocrinol, PL-91425 Lodz, Poland

[13] Univ Glasgow, Dept Human Nutr, Glasgow G3 2FR, Lanark, Scotland

[14] Univ Manchester, Hope Hosp, Manchester Acad Hlth Sci Ctr, Salford M6 8HD, Lancs, England

[15] Tartu Univ Clin, Androl Unit, United Labs, EE-50406 Tartu, Estonia

[16] Katholieke Univ Leuven, Leuven Univ Div Endocrinol, B-3000 Louvain, Belgium

[17] Univ Laval, Lab Mol Endocrinol & Oncol, Quebec City, PQ G1V 46A, Canada

[18] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Dept Endocrinol, Manchester M13 9WL, Lancs, England

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2010年 / 95卷 / 04期

关键词：

BINDING GLOBULIN SHBG; ANDROGEN RECEPTOR; LUTEINIZING-HORMONE; TESTOSTERONE LEVELS; ELDERLY-MEN; SERUM; RISK; INSULIN; VARIANT; AGE;

D O I：

10.1210/jc.2009-2071

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40-79 (mean +/- SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5 alpha-reductase type II (SRD5A2), 17 alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters. (J Clin Endocrinol Metab 95: 1898-1908, 2010)

引用

页码：1898 / 1908

页数：11

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