Gasser Benedikt, Kurz Johann, Mohaupt Markus
Department für Sport, Bewegung und Gesundheit, Universität Basel, 4052 Basel, Switzerland.
Intersci Research Association, Karl Morre Gasse 10, 8430 Leibnitz, Austria.
Diseases. 2021 Feb 1;9(1):13. doi: 10.3390/diseases9010013.
Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development.
Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry.
The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected ( = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected ( = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R < 0.22, all samples).
As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism.
表睾酮[E]长期以来一直被认为是一种无生物活性的雄激素。然而，最近已证明这种天然存在的睾酮差向异构体具有独特的抗雄激素活性。特别是睾酮/表睾酮（T/E）的比值似乎是关键因素，因为推测表睾酮对雄激素活性有抑制作用。由于在自闭症中暗示有较高的雄激素活性，因此我们推测自闭症儿童的T/E比值高于发育正常的儿童。
对22名自闭症女孩（体重指数18.7±4.3；平均年龄12.3±3.8岁）的尿液样本以及51名对照（体重指数17.0±2.6；平均年龄11.9±4岁），还有61名自闭症男孩（体重指数17.04±2；平均年龄11.9±2.5岁）和61名对照男孩（体重指数17.0±2.6；平均年龄11.1±3.0岁）的尿液样本进行气相色谱 - 质谱分析。
所有自闭症男孩的平均T/E比值为2.5±1.8，而发育正常男孩为2.4±1.3。未检测出自闭症男孩与发育正常男孩之间存在显著差异（P = 0.977）。自闭症女孩的平均T/E比值为1.4±0.9，而发育正常女孩为2.0±1.4，可检测到显著差异（P = 0.0285）。此外，进行了三次多项式分析，结果表明T/E比值与年龄相关，具有合理的决定系数（0.075 < R < 0.22，所有样本）。
由于全面的类固醇激素分析成本高昂且工作量大，我们希望找到一种易于应用的生物标志物来辅助自闭症的诊断。然而，由于仅分析了22名自闭症女孩这一相对较小的样本，且月经周期和青春期状态仅通过体重指数和年龄匹配部分可控，因此这一发现是否偶然仍存在疑问。尽管如此，一种推测可能是表睾酮对雄激素受体具有竞争性抑制作用，这可能有助于解释自闭症男孩患病率高于女孩的现象。据推测，由于在男孩中未检测到显著差异，从类固醇激素角度来看，这种作用可能不太相关，而先前在自闭症男孩和女孩中显示的如17/20 - 羟化酶活性改变等其他作用似乎更具相关性。为了验证目前关于自闭症中类固醇激素改变的发现，需要分析更大的样本，包括大量代谢物和酶促级联反应，以及自闭症女孩雄激素合成的旁路途径活性的作用。
