Baulieu E E, Robel P
Communications Hormonales (U33), INSERM, Bicêtre, France.
J Steroid Biochem Mol Biol. 1990 Nov 20;37(3):395-403. doi: 10.1016/0960-0760(90)90490-c.
The biosynthesis of neurosteroids proceeds through cholesterol side-chain cleavage, and gives rise to pregnenolone (P) and dehydroepiandrosterone (D). These steroids accumulate in the rat brain independently of the supply by peripheral endocrine glands. This led to the discovery of a steroid biosynthesis pathway in rat brain oligodendrocytes based on enzyme immunocytochemistry and conversion of radioactive precursors to C-21 steroids. Several biological functions have been proposed for P and D. They may serve as precursors of other steroids (such as progesterone and testosterone and their metabolites). They are implicated in the control of some behavioural activities. They have excitatory effects on neurons, and they modulate the function of GABAA-receptors. These observations may apply to all mammalian species including the human, and the physiological significance of neurosteroid synthesis needs further investigation. The relationship between steroids and cerebral function may be reconsidered in the light of a new fact: the existence of a biosynthetic pathway of these compounds from cholesterol, assured in the brain by the oligodendrocytes, glial cells which synthesize myelin.
神经甾体的生物合成通过胆固醇侧链裂解进行，产生孕烯醇酮（P）和脱氢表雄酮（D）。这些甾体在大鼠脑中积累，与外周内分泌腺的供应无关。基于酶免疫细胞化学以及放射性前体向C-21甾体的转化，这导致了在大鼠脑少突胶质细胞中发现了一种甾体生物合成途径。已提出P和D具有多种生物学功能。它们可能作为其他甾体（如孕酮和睾酮及其代谢物）的前体。它们与某些行为活动的控制有关。它们对神经元有兴奋作用，并调节GABAA受体的功能。这些观察结果可能适用于包括人类在内的所有哺乳动物物种，神经甾体合成的生理意义需要进一步研究。鉴于一个新的事实，甾体与脑功能之间的关系可能需要重新考虑：这些化合物从胆固醇开始的生物合成途径的存在，由少突胶质细胞（合成髓磷脂的神经胶质细胞）在脑中确保。
