A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary
A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary
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DOI：
10.1095/biolreprod66.1.77
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发表时间：
2002-01-01
影响因子：
3.6
通讯作者：
Hovatta, O
中科院分区：
文献类型：
--
作者：
Cheng, GJ;Zhang, WH;Hovatta, O
雌激素受体β(ERP)高表达，但ERα在小鼠卵巢的颗粒细胞中检测不到。在ERβ基因敲除(BERKO)小鼠中，卵泡发育异常，生育力极低。3周龄时，野生型(WT)与BERKO小鼠卵巢形态无明显差异，但5个月龄时，BERKO小鼠卵巢内可见大量的闭锁卵泡，而健康的腔后卵泡或黄体很少。在2岁时，与WT产仔小鼠的卵巢不同，BERKO小鼠的卵巢没有健康的卵泡，但有许多巨大的、泡沫状的、充满脂肪的基质细胞。BERKO小鼠晚期有腔卵泡和闭锁卵泡以雄激素受体(AR)和IGF-1受体高表达为特征。这些蛋白在WT小鼠腔前卵泡和腔早期卵泡的颗粒细胞中大量表达，而在WT小鼠的腔前卵泡和腔早期卵泡颗粒细胞中表达减弱。用抗雄激素药物氟他胺治疗15天后，BERKO小鼠的卵巢恢复了健康的晚腔卵泡和黄体。结果表明，在缺乏ERβ的情况下，AR失去了调节。由于雄激素促进原始卵泡的募集进入生长池，并导致晚期有腔卵泡闭锁，因此AR水平过高可能与BERKO小鼠卵泡闭锁和卵泡早期耗竭有关。
Estrogen receptor beta (ERP) is highly expressed, but ER alpha is not detectable in granulosa cells in the mouse ovary. In ER beta knockout (BERKO) mice, there is abnormal follicular development and very reduced fertility. At 3 wk of age, no significant morphologic differences were discernible between wild type (WT) and BERKO mouse ovaries, but by 5 mo of age, atretic follicles were abundant in BERKO mice and there were very few healthy late antral follicles or corpora lutea. At 2 yr of age, unlike the ovaries of their WT littermates, BERKO mouse ovaries were devoid of healthy follicles but had numerous large, foamy lipid-filled stromal cells. The late antral and atretic follicles in BERKO mice were characterized by a high level of expression of the androgen receptor (AR) and IGF-1 receptor. These proteins were abundantly expressed in granulosa cells of preantral and early antral follicles in both genotypes, but their expression was extinguished in late antral follicles of WT mice. Healthy late antral follicles and corpora lutea were restored in BERKO ovaries after 15 days of treatment of mice with the antiandrogen flutamide. The results suggest that in the absence of ER beta there was a loss of regulation of AR. Because androgens enhance recruitment of primordial follicles into the growth pool and cause atresia of late antral follicles, the inappropriately high level of AR probably is related to the follicular atresia and to the early exhaustion of follicles in BERKO mice.