Melcangi R C, Magnaghi V, Cavarretta I, Martini L, Piva F
Department of Endocrinology, University of Milan, Italy.
Neuroscience. 1998 Jul;85(2):569-78. doi: 10.1016/s0306-4522(97)00628-3.
The data here reported show that the gene expression of the glycoprotein Po and of the myelin basic protein, the major components of myelin in the peripheral nervous system, dramatically decreases with ageing in the sciatic nerve of normal male rats. A one-month treatment with dihydroprogesterone, the 5alpha-reduced derivative of progesterone, is able to partially restore the fall in Po gene expression occurring in the sciatic nerve of aged male rats, without significantly modifying the gene expression of the myelin basic protein. In cultures of neonatal Schwann cells (the peripheral nervous system elements involved in the synthesis of myelin), the addition of progesterone and of dihydroprogesterone significantly increases Po gene expression; the 3alpha-reduced metabolite of dihydroprogesterone, tetrahydroprogesterone proved to be even more effective. These data suggest that the effect of progesterone is linked to its conversion into dihydroprogesterone and especially into tetrahydroprogesterone, since Schwann cells possess the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase system. The data provide the first demonstration that ageing decreases the gene expression of two major components of the peripheral myelin in the sciatic nerve; they also show that this phenomenon may be partially reversed by progesterone derivatives, which might act by stimulating Po gene expression in the Schwann cells.
此处报告的数据表明，在正常雄性大鼠的坐骨神经中，髓磷脂在周围神经系统中的主要成分——糖蛋白Po和髓磷脂碱性蛋白的基因表达，会随着年龄增长而显著下降。用二氢孕酮（孕酮的5α-还原衍生物）进行为期一个月的治疗，能够部分恢复老年雄性大鼠坐骨神经中Po基因表达的下降，而不会显著改变髓磷脂碱性蛋白的基因表达。在新生雪旺细胞（参与髓磷脂合成的周围神经系统细胞）的培养物中，添加孕酮和二氢孕酮会显著增加Po基因表达；二氢孕酮的3α-还原代谢物四氢孕酮被证明更有效。这些数据表明，孕酮的作用与其转化为二氢孕酮，尤其是四氢孕酮有关，因为雪旺细胞拥有5α-还原酶-3α-羟基类固醇脱氢酶系统。这些数据首次证明，衰老会降低坐骨神经中周围髓磷脂两种主要成分的基因表达；它们还表明，这种现象可能会被孕酮衍生物部分逆转，孕酮衍生物可能通过刺激雪旺细胞中的Po基因表达起作用。
