Induction of mammary gland development in estrogen receptor-α knockout mice
Induction of mammary gland development in estrogen receptor-α knockout mice
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DOI：
10.1210/en.141.8.2982
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发表时间：
2000-08-01
期刊：
影响因子：
4.8
通讯作者：
Korach, KS
中科院分区：
文献类型：
--
作者：
Bocchinfuso, WP;Lindzey, JK;Korach, KS
乳腺从雌激素受体——一个！基因敲除（α ERKO）小鼠不发生导管形态发生或肺泡发育。内质网α信号的中断可能导致乳腺中雌激素应答基因产物的减少或导致α ERKO乳腺表型的促乳激素的减少。我们报道，循环PRL在雌性α ERKO小鼠中减少。在25日龄或12周龄α ERKO小鼠的肾包膜下植入年龄匹配的杂合ER α垂体异位移植物，可增加循环PRL和孕酮水平，并诱导乳腺发育。移植的α ERKO小鼠还具有肥大的黄体，这表明PRL在α ERKO卵巢中具有黄体性。相比之下，尽管PRL水平升高，但在α ERKO小鼠中，在垂体移植时切除卵巢可阻止乳腺发育。使用颗粒植入的激素替代表明，药理学剂量的雌二醇诱导有限的乳腺导管伸长，而雌二醇与黄体酮联合使用可刺激小叶肺泡发育。PRL单独或与黄体酮或雌二醇联合使用均不能诱导α ERKO乳腺生长。雌二醇和黄体酮是α EBKO乳腺结构发育所必需的，而PRL通过诱导卵巢黄体酮水平来促进这种发育。因此，α ERKO乳腺表型的表现是由于乳腺缺乏雌激素的直接作用和下丘脑/垂体轴雌激素信号的间接促进作用。
Mammary glands from the estrogen receptor-a! knockout (alpha ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted ER alpha signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute to the alpha ERKO mammary phenotype. We report that circulating PRL is reduced in the female alpha ERKO mouse. Implantation of an age-matched, heterozygous ER alpha pituitary isograft under the renal capsule of 25-day-old or 12-week-old alpha ERKO mice increased circulating PRL and progesterone levels, and induced mammary gland development. Grafted alpha ERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL is luteotropic in the alpha ERKO ovary. By contrast, ovariectomy at the time of pituitary grafting prevented mammary gland development in alpha ERKO mice despite elevated PRL levels. Hormone replacement using pellet implants demonstrated that pharmacological doses of estradiol induced limited mammary ductal elongation, and estradiol in combination with progesterone stimulated lobuloalveolar development. PRL alone or in combination with progesterone or estradiol did not induce alpha ERKO mammary growth. Estradiol and progesterone are required for the structural development of the alpha EBKO mammary gland, and PRL contributes to this development by inducing ovarian progesterone levels. Therefore, the manifestation of the alpha ERKO mammary phenotype appears due to the lack of direct estrogen action at the mammary gland and an indirect contributory role of estrogen signaling at the hypothalamic/pituitary axis.