TY - JOUR
T1 - Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats
AU - Holliday, Kate
AU - Limer, Kate L.
AU - Thomson, Wendy
AU - Platt, Hazel
AU - Payne, Debbie
AU - John, Sally L.
AU - Jiang, Min
AU - Boonen, Steven
AU - Borghs, Herman
AU - Vanderschueren, Dirk
AU - Adams, Judith E.
AU - Ward, Kate A.
AU - Bartfai, György
AU - Casanueva, Felipe
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 - Petrone, Luisa
AU - Cilotti, Antonio
AU - Slowikowska-Hilczer, Jolanta
AU - Walczak-Jedrzejowska, Renata
AU - Huhtaniemi, Ilpo
AU - Wu, Frederick
AU - Silman, Alan
AU - O'Neill, Terence
AU - Finn, Joseph
AU - Steer, Philip
AU - Tajar, Abdelouahid
AU - Lee, David
AU - Pye, Stephen
AU - Ocampo, Marta
AU - Lage, Mary
AU - Földesi, Imre
AU - Fejes, Imre
AU - Korrovitz, Paul
PY - 2009/1
Y1 - 2009/1
N2 - 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: The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length. Design: We conducted a multinational prospective cohort observational study with cross-sectional baseline data. Setting: This was a population survey of community-dwelling men. Participants: Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men. Main Outcome Measures: We measured 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. 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 estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels. Copyright © 2009 by The Endocrine Society.
AB - 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: The aim was to investigate the relationships between health status, various reproductive hormones, and the AR CAG repeat length. Design: We conducted a multinational prospective cohort observational study with cross-sectional baseline data. Setting: This was a population survey of community-dwelling men. Participants: Men (40-79 yr old; n = 3369) were randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2878 men. Main Outcome Measures: We measured 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. 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 estradiol of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or nearly totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions after aromatization of the higher T levels. Copyright © 2009 by The Endocrine Society.
KW - Adult
KW - Aged
KW - Aging/blood
KW - Cohort Studies
KW - Cross-Sectional Studies
KW - Estradiol/blood
KW - Follicle Stimulating Hormone/blood
KW - Humans
KW - Luteinizing Hormone/blood
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Receptors, Androgen/genetics
KW - Sex Hormone-Binding Globulin/analysis
KW - Testosterone/blood
KW - Trinucleotide Repeats
U2 - 10.1210/jc.2008-0848
DO - 10.1210/jc.2008-0848
M3 - Article
C2 - 18840639
SN - 1945-7197
VL - 94
SP - 277
EP - 284
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -