Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures

Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures
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DOI:
10.1016/s0304-3940(02)00146-5
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发表时间:
2002-05-03
影响因子:
2.5
通讯作者:
Finch, CE
Finch, CE
中科院分区:
医学4区
文献类型:
--
作者:
Rozovsky, I;Hoving, S;Finch, CE

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倍美力含有几种马雌激素,以及雌二醇(E2)作为次要成分,被广泛用于雌激素缺乏的替代治疗,但对其对脑细胞的直接作用知之甚少。在混合胶质细胞培养中,载脂蛋白E(apoE)和胶质细胞酸性蛋白(GFAP)可被雌激素诱导。GFAP诱导显示出倒U形E2剂量反应,在1 pM时诱导最大,而apoE mRNA诱导在100 pM时最大。GFAP和ApoE mRNA被马雌激素以以下顺序诱导:E2 =马雌激素>雌酮> 17 α-二氢马雌激素。然而,17 α-dihydroequilenin诱导apoE分泌与其他雌激素一样有效。apoE分泌比GFAP mRNA诱导对17 α-dihydroequilenin更大的反应可能是治疗上重要的,因为脑损伤期间的神经胶质瘢痕形成,其中GFAP诱导在抑制神经突生长中起主要作用,而apoE分泌支持神经突生长。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
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 > 17alpha-dihydroequilenin. However, the induction of apoE secretion by 17alpha-dihydroequilenin was as effective as by the other estrogens. The greater response of apoE secretion than GFAP mRNA induction to 17alpha-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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.