Molecular basis of Gender Dysphoria: androgen and estrogen receptor interaction
Molecular basis of Gender Dysphoria: androgen and estrogen receptor interaction
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DOI：
10.1016/j.psyneuen.2018.07.032
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发表时间：
2018-12-01
影响因子：
3.7
通讯作者：
Pasaro, Eduardo
中科院分区：
文献类型：
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作者：
Fernandez, Rosa;Guillamon, Antonio;Pasaro, Eduardo
背景：性类固醇受体的多态性与易性癖有关。然而，已发表的复制研究得出的结果不一致，可能是因为样本量有限和/或变性人群在烦躁不安和性取向发病方面的异质性。我们评估了雄激素受体（AR）、雌激素受体α（ER α）（ER α）和β（ER β），和芳香化酶（CYP 19 A1）在两个大的和同质的变性的男性对女性（MtF）和女性对男性（FtM）的population.Methods：每个多态性与易性癖的关联进行了研究与双重主题对照分析：在549名早发性男性化MtF变性者与728名男性对照以及425名女性化FtM与599名女性对照的同质人群中。协会和相互作用进行了调查，使用二进制logistic regression.Results：我们的数据显示，特定的等位基因和基因型组合的ER β，ER α和AR的有牵连的遗传基础的易性癖，MtF性别发展需要AR，这必须伴随着ER β。ER β和AR之间的反向等位基因相互作用是MtF人群的特征：当这些多态性中的任何一个是短的，另一个是长的。ER β和ER α也与FtM人群中的易性癖有关，尽管多态性之间没有相互作用。我们的数据表明ER β在人类典型的大脑分化中发挥关键作用。结论：ER β在人类男性和女性的性别分化中发挥关键作用。
Background: Polymorphisms in sex steroid receptors have been associated with transsexualism. However, published replication studies have yielded inconsistent findings, possibly because of a limited sample size and/or the heterogeneity of the transsexual population with respect to the onset of dysphoria and sexual orientation. We assessed the role of androgen receptor (AR), estrogen receptors alpha (ER alpha) and beta (ER beta), and aromatase (CYP19A1) in two large and homogeneous transsexual male-to-female (MtF) and female-to-male (FtM) populations.Methods: The association of each polymorphism with transsexualism was studied with a twofold subject -control analysis: in a homogeneous population of 549 early onset androphilic MtF transsexuals versus 728 male controls, and 425 gynephilic FtMs versus 599 female controls. Associations and interactions were investigated using binary logistic regression.Results: Our data show that specific allele and genotype combinations of ER beta, ER alpha and AR are implicated in the genetic basis of transsexualism, and that MtF gender development requires AR, which must be accompanied by ER beta. An inverse allele interaction between ER beta and AR is characteristic of the MtF population: when either of these polymorphisms is short, the other is long. ER beta and ER alpha are also associated with transsexualism in the FtM population although there was no interaction between the polymorphisms. Our data show that ER beta plays a key role in the typical brain differentiation of humans.Conclusion: ER beta plays a key role in human gender differentiation in males and females.