Different Forms of Oestrogen Rapidly Upregulate Cell Proliferation in the Dentate Gyrus of Adult Female Rats
Different Forms of Oestrogen Rapidly Upregulate Cell Proliferation in the Dentate Gyrus of Adult Female Rats
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DOI：
10.1111/j.1365-2826.2008.01809.x
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发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
Galea, L. A. M.
中科院分区：
文献类型：
--
作者：
Barha, C. K.;Lieblich, S. E.;Galea, L. A. M.
已知雌激素对成年啮齿动物的海马体产生显着的结构和功能影响。海马的齿状回在整个成年期保持产生神经元的能力，并且17 β-雌二醇已被证明影响成年雌性大鼠的海马神经发生。其他雌激素，如雌酮和17 α-雌二醇，对神经发生的影响尚未研究。本研究旨在研究17 β-雌二醇、苯甲酸雌二醇、雌酮和17 α-雌二醇在两个不同时间点对卵巢切除成年雌性大鼠细胞增殖的影响。年轻的卵巢切除雌性大鼠注射三种剂量之一的雌激素。在实验1中，大鼠暴露于激素4小时，在实验2中，大鼠暴露于激素30分钟之前，5-溴-2-脱氧尿苷注射标记增殖细胞及其后代。我们发现，年轻的卵巢切除女性的细胞增殖反应增加，大多数雌激素，除了雌二醇苯甲酸酯，30分钟后曝光。然而，雌激素给药较长的时间间隔是无效的，在增加细胞增殖。30分钟后，17 β-雌二醇和雌酮在低剂量（0.3 μ g）和高剂量（10 μ g）下增加细胞增殖，而17 α-雌二醇在中剂量（1 μ g）和高剂量下增加细胞增殖。本研究的结果表明，不同的雌激素迅速增加细胞增殖的剂量依赖性的方式，可能是通过一个非经典的，非基因组机制。未来的实验应该集中在进一步阐明每种雌激素所利用的特定途径上。这些结果具有重要的治疗意义，因为它可能会使用17 α-雌二醇和较低剂量的雌激素在激素替代疗法。
Oestrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. The dentate gyrus of the hippocampus retains the ability to produce neurones throughout adulthood and 17 beta-oestradiol has been shown to influence hippocampal neurogenesis in adult female rats. The effects of other oestrogens, such as oestrone and 17 alpha-oestradiol, on neurogenesis have not been investigated. The present study aimed to investigate the effects of 17 beta-oestradiol, oestradiol benzoate, oestrone, and 17 alpha-oestradiol on cell proliferation in ovariectomised adult female rats at two different time points. Young ovariectomised female rats were injected with one of the oestrogens at one of three doses. In Experiment 1, rats were exposed to the hormone for 4 h and, in Experiment 2, rats were exposed to the hormone for 30 min prior to 5-bromo-2-deoxyuridine injection to label proliferating cells and their progeny. We found that young ovariectomised females responded with increased cell proliferation to most oestrogens, except oestradiol benzoate, after 30 min of exposure. However, administration of oestrogens for a longer time interval was ineffective at increasing cell proliferation. After 30 min, 17 beta-oestradiol and oestrone increased cell proliferation at low (0.3 mu g) and high (10 mu g) doses, whereas 17 alpha-oestradiol increased cell proliferation at medium (1 mu g) and high doses. The results of the present study indicate that different oestrogens rapidly increase cell proliferation in a dose-dependent manner, possibly through a nonclassical, nongenomic mechanism. Future experiments should focus on further elucidating the specific pathways utilised by each oestrogen. These results have important therapeutic implications because it may be possible to use 17 alpha-oestradiol and lower doses of oestrogens in hormone replacement therapies.