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Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.

Huhtaniemi, Ilpo T; Pye, Stephen R; Limer, Kate L; Thomson, Wendy; O'Neill, Terence W; Platt, Hazel; Payne, Debbie; John, Sally L; Jiang, Min and Boonen, Steven, et al. (2009) In Journal of Clinical Endocrinology and Metabolism 94. p.277-284
Abstract
Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of... (More)
Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels. (Less)
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Contribution to journal
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published
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in
Journal of Clinical Endocrinology and Metabolism
volume
94
pages
277 - 284
publisher
The Endocrine Society
external identifiers
  • wos:000262260200042
  • pmid:18840639
  • scopus:58149400587
ISSN
1945-7197
DOI
10.1210/jc.2008-0848
language
English
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yes
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b1bd069e-f73b-4299-905f-f03fb698ccf7 (old id 1262446)
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http://www.ncbi.nlm.nih.gov/pubmed/18840639?dopt=Abstract
date added to LUP
2009-01-09 14:38:37
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2017-11-26 03:29:27
@article{b1bd069e-f73b-4299-905f-f03fb698ccf7,
  abstract     = {Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels.},
  author       = {Huhtaniemi, Ilpo T and Pye, Stephen R and Limer, Kate L and Thomson, Wendy and O'Neill, Terence W and Platt, Hazel and Payne, Debbie and John, Sally L and Jiang, Min and Boonen, Steven and Borghs, Herman and Vanderschueren, Dirk and Adams, Judith E and Ward, Kate A and Bartfai, György and Casanueva, Felipe 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 Wu, Frederick C W},
  issn         = {1945-7197},
  language     = {eng},
  pages        = {277--284},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.},
  url          = {http://dx.doi.org/10.1210/jc.2008-0848},
  volume       = {94},
  year         = {2009},
}