Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose‐ and time‐dependent manner
Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose‐ and time‐dependent manner
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DOI：
10.1002/cne.20385
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发表时间：
2005-01
影响因子：
2.5
通讯作者：
P. Tanapat;N. Hastings;E. Gould
中科院分区：
文献类型：
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作者：
P. Tanapat;N. Hastings;E. Gould
在以前的工作中，我们已经证明了在自然和实验条件下，成年海马结构中的细胞增殖都受到雌激素的调节。为了确定激素治疗的剂量或程序或黄体酮给药对这一调节的影响程度，我们使用S时相标记溴脱氧尿苷检测了不同的急性和慢性卵巢激素替代方案对细胞生产的影响。此外，我们还研究了外科卵巢激素耗竭对雌激素刺激细胞增殖的能力的长期影响，以及表达TuJ1(神经元表型的标记)或胶质纤维酸性蛋白(GFAP；星形胶质表型的标记)的新细胞的产生。在卵巢切除(OVX)动物中，用中等剂量(而不是低剂量或高剂量)的雌激素急性治疗可迅速促进细胞增殖，但这种作用可被黄体酮逆转。相比之下，在激素替代开始3周后，长期单独使用雌激素(持续或周期)或雌激素+孕酮(周期)替代的OVX动物没有表现出雌激素诱导的细胞增殖增加。在长期缺乏卵巢激素的动物中，中等剂量的雌激素急性治疗未能刺激细胞增殖，表达神经元表型的新细胞数量明显减少。总而言之，这些结果表明，卵巢激素的长期减少导致1)随着时间的推移，该系统对雌激素的反应减弱，2)神经元产生的减少，这不太可能通过标准的激素替代方案来逆转。J.Comp.神经。481：252-265,2005。©2004 Wiley-Liss Inc.
In previous work, we have demonstrated that cell proliferation in the adult hippocampal formation is regulated by estrogen under both natural and experimental conditions. To determine the extent to which this regulation is affected by the dose or schedule of hormone treatment, or progesterone administration, we examined the impact of different acute and chronic ovarian hormone replacement regimens on cell production using the S‐phase marker bromodeoxyuridine. Additionally, we investigated the long‐term impact of surgical ovarian hormone depletion on the capacity of estrogen to stimulate cell proliferation and the production of new cells that express either TuJ1 (a marker of neuronal phenotype) or glial fibrillary acidic protein (GFAP; a marker of astroglial phenotype). Acute treatment with a moderate, but not a low or a high, dose of estrogen rapidly increased cell proliferation in ovariectomized (OVX) animals, an effect that was reversed by the administration of progesterone. In contrast, OVX animals that were chronically replaced with either estrogen alone (continuous or cyclic) or estrogen plus progesterone (cyclic) did not exhibit an estrogen‐induced increase in cell proliferation 3 weeks following the onset of hormone replacement. In animals that were subjected to a prolonged absence of ovarian hormones, acute treatment with the moderate dose of estrogen failed to stimulate cell proliferation, and a decrease in the number of new cells expressing a neuronal phenotype was evident. Collectively, these results indicate that a prolonged reduction in ovarian hormones results in 1) a diminished responsiveness to estrogen over time in this system and 2) a decrease in neuron production that is unlikely to be reversible by standard regimens of hormone replacement. J. Comp. Neurol. 481:252–265, 2005. © 2004 Wiley‐Liss, Inc.