Möhlig Matthias, Jürgens Annette, Spranger Joachim, Hoffmann Kurt, Weickert Martin O, Schlösser Hans W, Schill Thilo, Brabant Georg, Schüring Andreas, Pfeiffer Andreas F H, Gromoll Jörg, Schöfl Christof
Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Berlin, Germany.
Eur J Endocrinol. 2006 Jul;155(1):127-30. doi: 10.1530/eje.1.02195.
Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR.
In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR).
Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR.
The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.
高雄激素血症是多囊卵巢综合征（PCOS）的核心特征，可能会加重PCOS患者常见的胰岛素抵抗（IR）。雄激素通过雄激素受体（AR）发挥作用。据报道，AR基因内的一个多态性CAG重复序列可调节其反式激活活性。因此，我们研究了睾酮与CAG重复长度多态性之间关于IR的假定相互作用。
在63名糖耐量正常的PCOS女性中，通过多元线性回归分析研究游离睾酮、双等位基因CAG重复长度及一个相乘交互项与IR的相关性，IR采用胰岛素抵抗稳态模型评估（HOMA-IR）表示。
游离睾酮与HOMA-IR相关。如交互项所示，睾酮对HOMA-IR的影响因AR CAG长度而改变。在对吸烟、年龄和体重指数进行校正后，这种交互作用仍然显著。虽然游离睾酮与HOMA-IR呈正相关，但交互项呈负相关。该模型解释了HOMA-IR变异的42.5%，预测在CAG长度短的携带者中，睾酮增加会导致IR增加。随着双等位基因CAG长度增加，这种效应减弱，直到CAG长度超过23时变为相反情况。使用CIGMA作为IR的另一种测量方法证实了这些结果。
AR内的CAG重复多态性改变了睾酮与IR之间的关联。因此，在评估睾酮对IR的影响时，似乎需要考虑PCOS女性的AR CAG重复多态性。
