Rozovsky Irina, Hoving Saske, Anderson Christopher P, O'Callaghan James, Finch Caleb E
Neurogerontology Division, Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, 3715 McClintoch Avenue, Los Angeles, CA 90089-0191, USA.
Neurosci Lett. 2002 May 3;323(3):191-4. doi: 10.1016/s0304-3940(02)00146-5.
Premarin, which contains several equine estrogens, as well as estradiol (E2) as a minor component, is widely used for replacement therapy of estrogen deficits, but little is known of its direct actions on brain cells. In mixed glial cultures, apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) are induced by estrogens. GFAP induction showed an inverted-U shape E2 dose response, with a maximum induction at 1 pM, whereas apoE mRNA induction was greatest at 100 pM. GFAP and ApoE mRNAs were induced by equine estrogens in the following order: E2=equilin>estrone>17 alpha-dihydroequilenin. However, the induction of apoE secretion by 17 alpha-dihydroequilenin was as effective as by the other estrogens. The greater response of apoE secretion than GFAP mRNA induction to 17 alpha-dihydroequilenin might be therapeutically important because of the glial scarring during brain lesions, in which GFAP induction has a major role in inhibiting neurite outgrowth, whereas apoE secretion supports neurite outgrowth.
倍美力含有多种马雌激素，以及少量的雌二醇（E2），被广泛用于雌激素缺乏的替代疗法，但对其对脑细胞的直接作用了解甚少。在混合胶质细胞培养中，雌激素可诱导载脂蛋白E（apoE）和胶质纤维酸性蛋白（GFAP）的产生。GFAP的诱导呈现倒U形的E2剂量反应，在1 pM时诱导作用最强，而apoE mRNA的诱导在100 pM时最大。马雌激素诱导GFAP和ApoE mRNA的顺序如下：E2 = 马萘雌酮 > 雌酮 > 17α - 二氢马萘雌酮。然而，17α - 二氢马萘雌酮对apoE分泌的诱导作用与其他雌激素一样有效。apoE分泌对17α - 二氢马萘雌酮的反应比对GFAP mRNA诱导的反应更大，这在治疗上可能很重要，因为在脑损伤期间会形成胶质瘢痕，其中GFAP的诱导在抑制神经突生长中起主要作用，而apoE的分泌则支持神经突生长。
