TY - JOUR
T1 - Effect of polymorphisms in selected genes involved in pituitary-testicular function on reproductive hormones and phenotype in aging men
AU - Huhtaniemi, Ilpo T.
AU - Pye, Stephen R.
AU - Holliday, Kate L.
AU - Thomson, Wendy
AU - O'Neill, Terence W.
AU - Platt, Hazel
AU - Payne, Debbie
AU - John, Sally L.
AU - Jiang, Min
AU - Bartfai, György
AU - Boonen, Steven
AU - Casanueva, Felipe F.
AU - Finn, Joseph D.
AU - Forti, Gianni
AU - Giwercman, Aleksander
AU - Han, Thang S.
AU - Kula, Krzysztof
AU - Lean, Michael E J
AU - Pendleton, Neil
AU - Punab, Margus
AU - Silman, Alan J.
AU - Vanderschueren, Dirk
AU - Labrie, Fernand
AU - Wu, Frederick C W
AU - Petrone, Luisa
AU - Corona, Giovanni
AU - Borghs, Herman
AU - Slowikowska-Hilczer, Jolanta
AU - Walczak-Jedrzejowska, Renata
AU - Steer, Philip
AU - Tajar, Abdelouahid
AU - Lee, David
AU - Lage, Mary
AU - Földesi, Imre
AU - Fejes, Imre
AU - Korrovitz, Paul
PY - 2010/4
Y1 - 2010/4
N2 - 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 pituitarytesticular 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:Atotal 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-α and -β (ESR1 and ESR2), steroid 5α-reductase type II (SRD5A2), 17α-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH β-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,andindices 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 down-stream effects may be too small to influence secondary phenotypic parameters. Copyright © 2010 by The Endocrine Society.
AB - 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 pituitarytesticular 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:Atotal 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-α and -β (ESR1 and ESR2), steroid 5α-reductase type II (SRD5A2), 17α-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH β-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,andindices 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 down-stream effects may be too small to influence secondary phenotypic parameters. Copyright © 2010 by The Endocrine Society.
U2 - 10.1210/jc.2009-2071
DO - 10.1210/jc.2009-2071
M3 - Article
C2 - 20173016
SN - 1945-7197
VL - 95
SP - 1898
EP - 1908
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -