Andrews W W, Mizejewski G J, Ojeda S R
Endocrinology. 1981 Nov;109(5):1404-13. doi: 10.1210/endo-109-5-1404.
Experiments were conducted to study, in a quantitative manner, the development of estradiol (E2)-positive feedback on LH release in the female rat. A Silastic capsule (20 mm in length/100 g BW) containing E2 dissolved in corn oil (400 micrograms/ml) reproduced first proestrous levels of serum E2 when implanted sc in juvenile rats of different ages (days 20-32). When similar capsules were implanted in infantile rats (days 10-18), serum E2, measured 2 days later, was found to be extremely elevated in 12- and 14-day-old rats (4-6 times higher than first proestrous levels), declining thereafter so that in 16- to 20-day-old rats the levels were only 2-fold greater than proestrous values. Serum levels of alpha-fetoprotein decreased markedly between days 12-28, and both normal and implant-produced serum E2 levels paralleled the decline in the protein titers. However, calculation of the total E2 binding capacity of alpha-fetoprotein indicated that in addition to binding to this protein, there are additional factors responsible for the persistence of E2 in the serum of infantile rats. A LH surge could not be induced in 12- or 14-day-old rats by a 48-h E2 pulse, despite the presence of substantial amounts of free E2, which exerted profound negative feedback effects. Between days 16-20, only E2 levels that were at least 2-fold higher than first proestrous values were effective in inducing a LH surge. Between days 22-34, a LH surge was elicited by serum E2 levels very similar to those seen during the first proestrus. By days 26-28, the profile of the LH surge was indistinguishable from that of the first preovulatory surge. Starting on day 26, and in addition to the LH surge elicited by the 48-h E2 pulse, an earlier surge occurred on the next day after E2 implantation. By day 30, the early LH surge became firmly established, and the late surge was no longer apparent. It is suggested that in the female rat, the development of E2-positive feedback comprises four phases: phase I, before day 16, in which the surge mechanism of the LH-releasing system is not developed; phase II, between days 16-20, in which E2 levels twice as high as those of first proestrus are necessary to activate the LH surge mechanism; phase III, which is initiated at the beginning of the juvenile period (approximately days 20-22) and in which the LH surge mechanism responds to E2 levels of preovulatory magnitude; and mechanism responds to E2 levels of preovulatory magnitude; and phase IV, which begins around days 26-28 and in which a 24-h exposure to E2 levels of preovulatory magnitude is sufficient to elicit a LH surge.
进行了实验，以定量方式研究雌二醇（E2）对雌性大鼠促黄体生成素（LH）释放的正反馈作用的发展。将含有溶解于玉米油（400微克/毫升）中的E2的硅橡胶胶囊（长度20毫米/体重100克）皮下植入不同年龄（20 - 32天）的幼年大鼠体内，可重现首次发情前期血清E2水平。当将类似的胶囊植入幼龄大鼠（10 - 18天）体内时，在植入2天后测量发现，12日龄和14日龄大鼠的血清E2极度升高（比首次发情前期水平高4 - 6倍），此后逐渐下降，以至于16 - 20日龄大鼠的E2水平仅比发情前期值高2倍。12 - 28日龄期间，血清甲胎蛋白水平显著下降，正常和植入产生的血清E2水平均与该蛋白滴度的下降平行。然而，对甲胎蛋白的总E2结合能力的计算表明，除了与该蛋白结合外，还有其他因素导致幼龄大鼠血清中E2持续存在。尽管存在大量游离E2并产生了深刻的负反馈作用，但48小时的E2脉冲仍无法在12日龄或14日龄大鼠中诱导LH峰。在16 - 20日龄期间，只有至少比首次发情前期值高2倍的E2水平才能有效诱导LH峰。在22 - 34日龄期间，血清E2水平与首次发情前期所见水平非常相似时可引发LH峰。到26 - 28日龄时，LH峰的特征与第一次排卵前峰难以区分。从26日龄开始，除了48小时E2脉冲引发的LH峰外，在E2植入后的第二天还会出现较早的峰。到30日龄时，早期LH峰已牢固确立，晚期峰不再明显。有人提出，在雌性大鼠中，E2正反馈作用的发展包括四个阶段：第一阶段，16日龄之前，LH释放系统的峰机制尚未发育；第二阶段，16 - 20日龄之间，E2水平需比首次发情前期高两倍才能激活LH峰机制；第三阶段，在幼年初期（约20 - 22日龄）开始，LH峰机制对排卵前水平的E2作出反应；第四阶段，大约在26 - 28日龄开始，24小时暴露于排卵前水平的E2足以引发LH峰。
