Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder mainly affecting the structure and functions of the striatum, cerebral cortex and hippocampus leading to movement disorders, cognitive dysfunctions and emotional disturbances. The onset of HD has been linked to a pathogenic CAG repeat expansion in the huntingtin (HTT) gene that encodes for the polyglutamine (polyQ) stretches in the huntingtin (Htt) protein. Notably, the neuropathogenic events of the mutant HTT gene appear to be primed during adulthood and magnified along the ageing process. While the normal Htt protein is vital for the neuronal differentiation and neuroprotection, experimental HD models and postmortem human HD brains have been characterized by neurodegeneration and defects in neuroregenerative plasticity in the basal ganglia and limbic system including the hippocampus. Besides gonadal dysfunctions, reduced androgen levels and abnormal hypothalamic-pituitary-gonadal (HPG) axis have increasingly been evident in HD. Recently, ageing-related changes in levels of steroid sex hormones have been proposed to play a detrimental effect on the regulation of hippocampal neurogenesis in the adult brain. Considering its adult-onset nature, a potential relationship between dysregulation in the synthesis of sex steroid hormones and the pathogenesis of the mutant HTT gene appears to be an important clinical issue in HD. While the hippocampus and testis are the major sites of steroidogenesis, the presence of Htt in both areas is conclusively evident. Hence, the expression of the normal HTT gene may take part in the steroidogenic events in aforementioned organs in the physiological state, whereas the mutant HTT gene may cause defects in steroidogenesis in HD. Therefore, this review article comprehends the potential relationship between the gonadal dysfunctions and abnormal hippocampal plasticity in HD and represents a hypothesis for the putative role of the HTT gene in the regulation of steroidogenesis in gonads and in the brain.

中文翻译：

---

在亨廷顿氏病中，与睾丸萎缩和下丘脑-垂体-性腺（HPG）轴失调相关的神经再生可塑性恶化：亨廷顿基因在类固醇生成中的推定作用。

亨廷顿舞蹈病（HD）是一种常染色体显性遗传进行性神经退行性疾病，主要影响纹状体，大脑皮层和海马的结构和功能，导致运动障碍，认知功能障碍和情绪障碍。HD的发作与亨廷顿蛋白（HTT）基因中的致病性CAG重复扩增有关，该基因编码亨廷顿蛋白（Htt）蛋白中的聚谷氨酰胺（polyQ）片段。值得注意的是，突变型HTT基因的神经致病性事件似乎在成年期间已引发，并随着衰老过程而放大。正常的Htt蛋白对于神经元的分化和神经保护至关重要，实验性HD模型和死后人类HD大脑的特征在于神经变性以及基底神经节和包括海马在内的边缘系统的神经再生可塑性缺陷。除了性腺功能障碍外，HD患者中雄激素水平降低和下丘脑-垂体-性腺（HPG）轴异常也越来越明显。近来，已提出类固醇性激素水平的与衰老有关的变化对成年大脑海马神经发生的调节起有害作用。考虑到其成年发作的性质，性类固醇激素合成中的失调与突变型HTT基因的发病机理之间的潜在关系似乎是HD的重要临床问题。海马和睾丸是类固醇生成的主要部位，在这两个区域中Htt的存在是明显的。因此，正常HTT基因的表达可能参与上述处于生理状态的器官中的类固醇生成事件，而突变型HTT基因可能导致HD中类固醇生成的缺陷。因此，这篇综述文章理解了性腺功能障碍和HD中海马可塑性异常之间的潜在关系，并提出了有关HTT基因在性腺和大脑中类固醇生成调控中的假定作用的假设。