Abstract：
An important aspect of the neuromodulatory and neuroprotective actions exerted by neuroactive steroids is that they are sex-specific, as determined by the sexually dimorphic levels of these molecules in plasma and the nervous tissue. Thus, the identification of the factors that generate the sex-dimorphic levels of neuroactive steroids may be crucial from a neuroprotectant perspective. The main driver for sex determination in mammals is the SRY gene and the subsequent presence of a specific gonad: testes for males and ovaries for females, thus producing hormonal compounds, primarily androgens and estrogens, respectively. Nowadays, it is well established that despite the relevance of gonads, other factors control sexual features, and, among them, sex chromosome complement is highly relevant. In this study, neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in the hypothalamus, the hippocampus, and plasma of the four core genotype mouse model, to determine the relative contribution of sex chromosome complement and gonads in determining their sex dimorphic levels. The data obtained reveal that although gonads are the main contributing factor for sex differences in neuroactive steroid levels, the levels of some neuroactive steroids, including testosterone, are also influenced in brain and plasma by tissue-specific actions of sex chromosomes. The data presented here adds a new piece to the puzzle of steroid level regulation, which may be useful in designing sex-specific neuroprotective approaches to pathological conditions affecting the nervous system.
摘要：
神经活性类固醇发挥的神经调节和神经保护作用的一个重要方面是它们具有性别特异性，取决于血浆和神经组织中这些分子的性别二态水平。因此，从神经保护剂的角度来看,确定产生神经活性类固醇性别二态水平的因素可能是至关重要的.哺乳动物性别决定的主要驱动因素是SRY基因和随后存在的特定性腺：男性的睾丸和女性的卵巢，从而产生荷尔蒙化合物，主要是雄激素和雌激素，分别。如今,众所周知，尽管性腺具有相关性，其他因素控制性特征，and,其中,性染色体补体是高度相关的。在这项研究中,神经活性类固醇在下丘脑通过液相色谱-串联质谱法进行评估，四种核心基因型小鼠模型的海马和血浆，确定性染色体补体和性腺在确定其性别二态水平中的相对贡献。获得的数据表明，尽管性腺是神经活性类固醇水平性别差异的主要因素，一些神经活性类固醇的水平，包括睾丸激素,在大脑和血浆中也受到性染色体的组织特异性作用的影响。这里提供的数据为类固醇水平调节的难题增加了一个新的部分，这可能有助于设计针对影响神经系统的病理状况的性别特异性神经保护方法。
