Endocrine Abstracts

Objective: The human androgen recteptor (AR) contains a polyglutamine and a polyglycine stretch that are highly polymorphic and are coded by a CAG and GGN repeat, respectively, in exon 1 of the AR gene. Although in vitro studies indicated a possible effect on AR gene tanscription and clinical observations suggest a modulation of androgen action, the functional significance of the GGN repeat remains unclear.

We wanted to assess whether the GGN repeat affects serum T levels in healthy men, which is the expected outcome through feedback regulation if the GGN repeat influences androgen action as shown to be the case for the CAG repeat.

Design and patients: A population based cohort study including 1485 healthy young, middle-aged, and elderly men. The study protocol was approved by the ethical committee of the Ghent University Hospital and written informed consent was obtained from all participants.

Measurement: Testosterone (T) and luteinizing hormone levels were determined by immunoassay; free T levels (FT) were calculated. Genotyping of the GGN repeat was performed using the sequencing technique.

Results: The GGN repeat number was significantly associated with circulating T and FT levels (β=0.063, P=0.011 and β=0.058, P=0.006 respectively). However, taking into account that age, BMI and CAG are already in the regression model, the GGN repeat could explain only 0.4 percent of the variation of both T and FT.

Conclusion: To our knowledge, this study is the first to find a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study adds credence to the view that the polyglycine tract in the AR modulates AR action, this effect appears to be only small so that its clinical relevancy remains questionable.