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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
  • Thang S Han
  • Krzysztof Kula
  • Michael E J Lean
  • Neil Pendleton
  • Margus Punab
  • Alan J Silman
  • Frederick C W Wu
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Obstetrics, Gynecology and Reproductive Medicine
Original languageEnglish
Pages (from-to)277-284
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes