Divisions of Pediatric Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Biol Reprod. 2009 Sep;81(3):488-96. doi: 10.1095/biolreprod.108.075259. Epub 2009 May 13.
Mice lacking estrogen receptor alpha in the pituitary gonadotroph (PitEsr1KO) were generated to determine the physiologic role of pituitary estrogen signaling in the reproductive axis. PitEsr1KO female mice are subfertile or infertile and have elevated levels of serum luteinizing hormone (LH) and LH beta subunit gene expression, reflecting a lack of estrogen negative feedback effect on the gonadotroph. While serum LH values are elevated in PitEsr1KO mice, the degree of elevation is much less than that observed in ESR1-null mice, indicating that the hypothalamus must also have an important role in estrogen negative feedback. PitEsr1KO mice also demonstrate a defect in estrogen positive feedback, as surge LH values and estrous cyclicity are absent in these mice. Although sex steroid feedback in the reproductive axis is thought to involve discrete anatomic regions that mediate either a positive or negative estrogen effect, PitEsr1KO mice demonstrate novel evidence that localizes both estrogen positive feedback and estrogen negative feedback to the gonadotroph, which suggests that they may be mechanistically related.
为了确定垂体雌激素信号在生殖轴中的生理作用，我们生成了缺乏垂体促性腺激素中雌激素受体 α（PitEsr1KO）的小鼠。PitEsr1KO 雌性小鼠繁殖力低下或不育，血清促黄体生成激素（LH）和 LHβ亚基基因表达水平升高，反映出雌激素对促性腺激素缺乏负反馈作用。虽然 PitEsr1KO 小鼠的血清 LH 值升高，但升高的程度远低于 ESR1 缺失小鼠，这表明下丘脑在雌激素负反馈中也具有重要作用。PitEsr1KO 小鼠还表现出雌激素正反馈的缺陷，因为这些小鼠缺乏 LH 激增值和动情周期性。虽然认为生殖轴中的性激素反馈涉及介导雌激素正或负效应的不同解剖区域，但 PitEsr1KO 小鼠提供了将雌激素正反馈和雌激素负反馈都定位于促性腺激素的新证据，这表明它们可能在机制上相关。
