Neuroactive steroids, molecules produced from cholesterol in steroidogenic cells (i.e., peripheral glands and nervous system) are physiological modulators and protective agents of nervous function. A possible role for neuroactive steroids in the sex-dimorphic clinical manifestation, onset and progression of Multiple Sclerosis (MS) has been recently suggested. To explore this possibility, we assessed the synthesis of the first steroidogenic product (pregnenolone; PREG) in the spinal cord of experimental autoimmune encephalomyelitis rats, a MS model. Data obtained indicate that the synthesis of PREG in the spinal cord is altered by the pathology in a sex-dimorphic way and depending on the pathological progression. Indeed, in male spinal cord the synthesis was already decreased at the acute phase of the disease (i.e., 14 days post induction - dpi) and maintained low during the chronic phase (i.e., 45 dpi), while in females this effect was observed only at the chronic phase. Substrate availability had also a role in the sex-dimorphic kinetics. Indeed, at the chronic phase, male animals showed a reduction in the levels of free cholesterol coupled to alteration of cholesterol metabolism into oxysterols; these effects were not observed in female animals. These findings suggest that the comprehension of the neurosteroidogenic processes could be relevant to better understand the sexual dimorphism of MS and to possibly design sex-oriented therapeutic strategies based on neuroactive steroids.

中文翻译：

---

多发性硬化症动物模型中的性别二态性：集中于孕烯醇酮的合成。

神经活性类固醇是由类固醇生成细胞（即外周腺体和神经系统）中的胆固醇产生的分子，是神经调节剂和神经功能的保护剂。最近有人建议神经活性类固醇在多发性硬化症（MS）的性别-双态临床表现，发作和进展中可能发挥作用。为了探索这种可能性，我们评估了实验性自身免疫性脑脊髓炎大鼠（一种MS模型）的脊髓中第一个类固醇生成产物（孕烯醇酮； PREG）的合成。所获得的数据表明，脊髓中PREG的合成被病理改变为性别双态性并取决于病理进展。实际上，在男性脊髓中，该疾病的急性期合成已经减少（即，诱导后14天（dpi），并在慢性阶段保持较低水平（即45 dpi），而在女性中，只有在慢性阶段才观察到这种作用。底物的可用性在性别-双态动力学中也有作用。的确，在慢性期，雄性动物的游离胆固醇水平降低，胆固醇代谢转变为氧固醇。在雌性动物中未观察到这些作用。这些发现表明，神经甾体生成过程的理解可能与更好地理解MS的性二态性以及可能设计基于神经活性甾体的性取向治疗策略有关。底物的可用性在性别-双态动力学中也有作用。的确，在慢性期，雄性动物的游离胆固醇水平降低，胆固醇代谢转变为氧固醇。在雌性动物中未观察到这些作用。这些发现表明，神经甾体生成过程的理解可能与更好地理解MS的性二态性以及可能设计基于神经活性甾体的性取向治疗策略有关。底物的可用性在性别-双态动力学中也有作用。的确，在慢性期，雄性动物的游离胆固醇水平降低，胆固醇代谢转变为氧固醇。在雌性动物中未观察到这些作用。这些发现表明，神经甾体生成过程的理解可能与更好地理解MS的性二态性以及可能设计基于神经活性甾体的性取向治疗策略有关。