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

Huhtaniemi, Ilpo T; Pye, Stephen R; Holliday, Kate L; Thomson, Wendy; O'Neill, Terence W; Platt, Hazel; Payne, Debbie; John, Sally L; Jiang, Min and Bartfai, György, et al. (2010) In The Journal of clinical endocrinology and metabolism 95. p.1898-1908
Abstract
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... (More)
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 5alpha-reductase type II (SRD5A2), 17alpha-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. (Less)
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The Journal of clinical endocrinology and metabolism
volume
95
pages
1898 - 1908
publisher
The Endocrine Society
external identifiers
  • WOS:000276402300051
  • PMID:20173016
  • Scopus:77951634472
ISSN
1945-7197
DOI
10.1210/jc.2009-2071
language
English
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yes
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1b2bb06d-4e3c-46f0-b4ef-b5f12a210d60 (old id 1552427)
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http://www.ncbi.nlm.nih.gov/pubmed/20173016?dopt=Abstract
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2010-03-03 12:55:05
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2016-11-09 14:39:57
@misc{1b2bb06d-4e3c-46f0-b4ef-b5f12a210d60,
  abstract     = {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 5alpha-reductase type II (SRD5A2), 17alpha-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.},
  author       = {Huhtaniemi, Ilpo T and Pye, Stephen R and Holliday, Kate L and Thomson, Wendy and O'Neill, Terence W and Platt, Hazel and Payne, Debbie and John, Sally L and Jiang, Min and Bartfai, György and Boonen, Steven and Casanueva, Felipe F and Finn, Joseph D and Forti, Gianni and Giwercman, Aleksander and Han, Thang S and Kula, Krzysztof and Lean, Michael E J and Pendleton, Neil and Punab, Margus and Silman, Alan J and Vanderschueren, Dirk and Labrie, Fernand and Wu, Frederick C W},
  issn         = {1945-7197},
  language     = {eng},
  pages        = {1898--1908},
  publisher    = {ARRAY(0xa95d128)},
  series       = {The Journal of clinical endocrinology and metabolism},
  title        = {Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men.},
  url          = {http://dx.doi.org/10.1210/jc.2009-2071},
  volume       = {95},
  year         = {2010},
}