Dipartimento di Neuroscienze "Rita Levi Montalcini", Università degli Studi di Torino and Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano 10126, Torino, Italy.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Neurosci Biobehav Rev. 2016 Aug;67:2-8. doi: 10.1016/j.neubiorev.2016.04.017. Epub 2016 Apr 23.
Sex differences are present both in the genotype and in the phenotype of all vertebrates, and they have been evidenced also within the central and peripheral nervous system. Earlier studies on brain sex differences suggested a relatively simple view based on (1) the presence of sexually dimorphic circuits in the hypothalamus (or in regions related to reproductive behaviors), (2) the action of gonadal hormones to masculinize the brain, and (3) the gonadal steroids' action to modulate gene transcription through nuclear receptors. These assumptions are today contradicted by the findings accumulated in the last 20 years. We know now that mechanisms determining sexual dimorphisms may vary according to location and species, and may involve several factors, as genes, epigenetic factors, gonadal hormones and neurosteroids. Sex differences were also revealed by epidemiological studies in several neural pathologies. This suggests that the approach to understand the genesis of these pathologies, should involve specific attention to interactions among genes, gonadal and brain-born steroid hormones, epigenetic and environmental factors.
性别的差异不仅存在于所有脊椎动物的基因型和表型中，而且也存在于中枢和外周神经系统中。早期关于大脑性别差异的研究提出了一个相对简单的观点，该观点基于以下几点：（1）下丘脑（或与生殖行为相关的区域）中存在性别二态性回路；（2）性腺激素使大脑雄性化；（3）性腺类固醇通过核受体调节基因转录。这些假设如今已被过去 20 年积累的研究结果所否定。我们现在知道，决定性别二态性的机制可能因位置和物种而异，并且可能涉及多种因素，如基因、表观遗传因素、性腺激素和神经甾体。流行病学研究在多种神经病理学中也揭示了性别差异。这表明，要了解这些病理学的起源，就应该特别注意基因、性腺和脑源性类固醇激素、表观遗传和环境因素之间的相互作用。
