Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression
Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression
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DOI：
10.1074/jbc.m010043200
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发表时间：
2001-04-06
影响因子：
4.8
通讯作者：
Shimasaki, S
中科院分区：
文献类型：
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作者：
Otsuka, F;Yamamoto, S;Shimasaki, S
我们最近报道了卵母细胞来源的骨形态发生蛋白-15 （BMP-15）可以直接调节大鼠颗粒细胞的促卵泡激素（FSH）作用。在这里，我们研究了BMP-15效应的潜在机制。单独使用BMP-15对编码类固醇急性调节蛋白、P450侧链切割酶、P450芳香化酶、3 β -羟基类固醇脱氢酶、黄体生成素受体和抑制素/激活素亚基的mrna的基础表达没有显著影响。然而，BMP-15显著抑制了fsh诱导的这些信息的增加。与之形成鲜明对比的是，BMP-15并没有改变福斯克林诱导的这些转录本的水平，因此，BMP-15对FSH作用的抑制作用一定是在cAMP信号传导的上游。接下来我们检测了FSH受体mRNA表达的变化。有趣的是，BMP-15在基底细胞和FSH刺激细胞中都严重降低了FSH受体mRNA的水平。为了确定这种影响是否在FSH功能水平上，我们研究了BMP-15对FSH生物活性的影响，与mRNA数据一致，BMP-15抑制FSH的生物反应，但不抑制福斯克林。基于这些结果，我们提出BMP-15通过其抑制FSH受体表达的能力是FSH作用的重要决定因素。由于FSH在卵泡生长和发育中起着至关重要的作用，我们的研究结果可能对理解卵母细胞生长因子如何促进卵泡发生有新的意义。
We have recently reported that oocyte-derived bone morphogenetic protein-15 (BMP-15) can directly modulate follicle-stimulating hormone (FSH) action in rat granulosa cells. Here, we investigate underlying mechanisms of this BMP-15 effect. Treatment with BMP-15 alone exerted no significant effect on the basal expression of mRNAs encoding steroidogenic acute regulatory protein, P450 side chain cleavage enzyme, P450 aromatase, 3 beta -hydroxysteroid dehydrogenase, luteinization hormone receptor, and inhibin/activin subunits. However, BMP-15 markedly inhibited the FSH-induced increases in these messages. In striking contrast, BMP-15 did not change the forskolin-induced levels of these transcripts, Thus, the inhibitory effect of BMP-15 on FSH action must be upstream of cAMP signaling. We next examined changes in FSH receptor mRNA expression. Interestingly, BMP-15 severely reduced the levels of FSH receptor mRNA in both basal and FSH-stimulated cells. To determine whether this effect was at the level of FSH function, we investigated the effect of BMP-15 on FSH bioactivity, Consistent with the mRNA data, BMP-15 inhibited the biological response of FSH, but not that of forskolin. Based on these results, we propose that BMP-15 is an important determinant of FSH action through its ability to inhibit FSH receptor expression. Because FSH plays an essential role in follicle growth and development, our findings could have new implications for understanding how oocyte growth factors contribute to folliculogenesis.