Ormerod B K, Galea L A
Department of Psychology and Graduate Neuroscience Program, The University of British Columbia, BC, V6T 1Z4, Vancouver, Canada.
Neuroscience. 2001;102(2):369-79. doi: 10.1016/s0306-4522(00)00474-7.
Galea and McEwen [Galea and McEwan (1999) Neuroscience 89, 955-964] found that cell proliferation was suppressed in female meadow voles trapped during the breeding season relative to females trapped during the non-breeding season. We investigated the effect of reproductive status and estradiol level on cell proliferation and cell survival in adult laboratory-reared female meadow voles to control for the variables of age, experience and pregnancy that could confound the results derived from a wild sample. Voles were housed in either a long- or short-photoperiod to simulate season and a male or female cage partner was introduced to influence reproductive status. Because females are reflex ovulators, exposure to a male rapidly induces behavioural estrous and high levels of estradiol. Forty-eight hours after introducing a cage partner, we injected either bromodeoxyuridine or [3H]thymidine to mark cell synthesis and then examined labelled cells 2h (cell proliferation) or five weeks (cell survival) later, respectively. To determine whether estradiol mimicked the effect of reproductive status, groups of reproductively inactive females were given a single injection of estradiol benzoate (10 microg) either four or 48h prior to bromodeoxyuridine labelling. The density of proliferating cells in the granule cell layer and the hilus was elevated in reproductively inactive females compared to reproductively active females and was correlated negatively with serum estradiol level. Exposure to estradiol benzoate initially increased cell proliferation (within 4h) but subsequently suppressed cell proliferation (within 48h). In addition, the density of surviving cells was greater in reproductively inactive females relative to reproductively active females but reproductively active females had a greater rate of cell survival than did reproductively inactive females. Reproductive status did not influence the number of pyknotic cells in the dentate gyrus (at either 2h or five weeks).We conclude that reproductive status regulates cell proliferation in adult female meadow voles, possibly via an estradiol-regulated mechanism. The results from the present study showed that reproductively active female meadow voles have suppressed rates of cell proliferation in the dentate gyrus relative compared with reproductively inactive female meadow voles. Administering estradiol initially (within 4h) elevates the cell proliferation within the dentate gyrus of adult females but subsequently (within 48h) suppresses cell proliferation. However, more new cells survived in females with high endogenous levels of estradiol (reproductively active females). In conclusion, reproductive status regulates the level of cell proliferation and survival through a complex estradiol regulated mechanism(s).
加利亚和麦克尤恩[加利亚和麦克尤恩（1999年），《神经科学》89卷，955 - 964页]发现，与在非繁殖季节捕获的雌性草地田鼠相比，在繁殖季节捕获的雌性草地田鼠的细胞增殖受到抑制。我们研究了生殖状态和雌二醇水平对成年实验室饲养的雌性草地田鼠细胞增殖和细胞存活的影响，以控制可能混淆来自野生样本结果的年龄、经验和怀孕等变量。将田鼠饲养在长光照周期或短光照周期中以模拟季节，并引入雄性或雌性笼伴以影响生殖状态。由于雌性是反射性排卵动物，接触雄性会迅速诱导行为发情和高水平的雌二醇。引入笼伴48小时后，我们注射溴脱氧尿苷或[³H]胸腺嘧啶核苷以标记细胞合成，然后分别在2小时后（细胞增殖）或五周后（细胞存活）检查标记细胞。为了确定雌二醇是否模拟了生殖状态的影响，在溴脱氧尿苷标记前4小时或48小时，对未处于生殖活跃状态的雌性田鼠组单次注射苯甲酸雌二醇（10微克）。与处于生殖活跃状态的雌性相比，未处于生殖活跃状态的雌性颗粒细胞层和齿状回中的增殖细胞密度升高，且与血清雌二醇水平呈负相关。接触苯甲酸雌二醇最初会增加细胞增殖（4小时内），但随后会抑制细胞增殖（48小时内）。此外，未处于生殖活跃状态的雌性中存活细胞的密度相对于处于生殖活跃状态的雌性更大，但处于生殖活跃状态的雌性细胞存活速率比未处于生殖活跃状态的雌性更高。生殖状态不影响齿状回中固缩细胞的数量（2小时或五周时均如此）。我们得出结论，生殖状态可能通过一种雌二醇调节机制来调节成年雌性草地田鼠的细胞增殖。本研究结果表明，与未处于生殖活跃状态的雌性草地田鼠相比，处于生殖活跃状态的雌性草地田鼠齿状回中的细胞增殖速率受到抑制。最初（4小时内）给予雌二醇会提高成年雌性齿状回内的细胞增殖，但随后（48小时内）会抑制细胞增殖。然而，内源性雌二醇水平高的雌性（处于生殖活跃状态的雌性）中有更多新细胞存活。总之，生殖状态通过一种复杂的雌二醇调节机制来调节细胞增殖和存活水平。
