Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats

Ilpo T. Huhtaniemi, Stephen R. Pye, Kate L. Limer, Wendy Thomson, Terence W. O'Neill, Hazel Platt, Debbie Payne, Sally L. John, Min Jiang, Steven Boonen, Herman Borghs, Dirk Vanderschueren, Judith E. Adams, Kate A. Ward, György Bartfai, Felipe Casanueva, Joseph D. Finn, Gianni Forti, Aleksander Giwercman, Thang S. HanKrzysztof Kula, Michael E.J. Lean, Neil Pendleton, Margus Punab, Alan J. Silman, Frederick C.W. Wu, Luisa Petrone, Antonio Cilotti, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska, Ilpo Huhtaniemi, Frederick Wu, Alan Silman, Terence O'Neill, Joseph Finn, Philip Steer, Abdelouahid Tajar, David Lee, Stephen Pye, Marta Ocampo, Mary Lage, Imre Földesi, Imre Fejes, Paul Korrovitz

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105 Citations (Scopus)

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: 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.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number1
DOIs
Publication statusPublished - Jan 2009

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Huhtaniemi, I. T., Pye, S. R., Limer, K. L., Thomson, W., O'Neill, T. W., Platt, H., Payne, D., John, S. L., Jiang, M., Boonen, S., Borghs, H., Vanderschueren, D., Adams, J. E., Ward, K. A., Bartfai, G., Casanueva, F., Finn, J. D., Forti, G., Giwercman, A., ... Korrovitz, P. (2009). Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. Journal of Clinical Endocrinology and Metabolism, 94(1), 277-284. https://doi.org/10.1210/jc.2008-0848