Baulieu E E
Communications Hormonales (U 33) INSERM and Biochimie Hormonale, Faculté de Médecine Paris-Sud, Bicêtre, France.
Biol Cell. 1991;71(1-2):3-10. doi: 10.1016/0248-4900(91)90045-o.
"Neurosteroids" accumulate in the central nervous system independently of supply by peripheral endocrine glands. Dehydroepiandrosterone (DHA) and pregnenolone (delta 5P) were first found in the rat brain. Then, a steroid biosynthetic pathway was demonstrated in oligodendrocytes, mostly by enzyme immunocytochemistry and biochemical studies in primary cultures of glial cells, where the formation, from appropriate radioactive precursors, of delta 5P, delta 5-pregn-3 beta, 20 alpha-diol (20 alpha-DH delta 5P), progesterone (P), 5 alpha-pregnane-3,20-dione (5 alpha-DHP) and 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-THP), as well as estrogen-induced nuclear progesterone receptor (PR) was observed. Several biological effects of neurosteroids have been observed, such as electrical stimulation of neurones, involvement in behaviorial activities, modulation of GABAA-receptor (GABAA-R) function (potentiated by 3 alpha, 5 alpha-THP and its 21-hydroxyderivative, antagonized by delta 5P- and DHA-sulfates) and growth/differentiation of glial cells in vitro. Preliminary findings suggest that the neurosteroid concept applies to all mammalian species, including man. Further investigations should assess the pathophysiological significance of the synthesis of neurosteroids and decipher their mechanisms of action via nuclear and membrane receptors.
“神经甾体”在中枢神经系统中蓄积，与外周内分泌腺的供应无关。脱氢表雄酮（DHA）和孕烯醇酮（δ5P）最初在大鼠脑中被发现。随后，在少突胶质细胞中证实了一条甾体生物合成途径，这主要是通过酶免疫细胞化学和神经胶质细胞原代培养中的生化研究得出的。在这些研究中，观察到从合适的放射性前体形成了δ5P、δ5-孕甾-3β,20α-二醇（20α-DHδ5P）、孕酮（P）、5α-孕烷-3,20-二酮（5α-DHP）和3α-羟基-5α-孕烷-20-酮（3α,5α-THP），以及雌激素诱导的核孕酮受体（PR）。已观察到神经甾体的多种生物学效应，如对神经元的电刺激、参与行为活动、调节GABAA受体（GABAA-R）功能（3α,5α-THP及其21-羟基衍生物可增强该功能，δ5P-和DHA-硫酸盐则起拮抗作用）以及体外神经胶质细胞的生长/分化。初步研究结果表明，神经甾体的概念适用于包括人类在内的所有哺乳动物物种。进一步的研究应评估神经甾体合成的病理生理学意义，并阐明它们通过核受体和膜受体的作用机制。
