Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells.
Interaction between gonadotropin-releasing hormone and bone morphogenetic protein-6 and -7 signaling in LβT2 gonadotrope cells.
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DOI：
10.1016/j.mce.2011.08.001
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发表时间：
2012-01-02
影响因子：
4.1
通讯作者：
Lawson, Mark A.
中科院分区：
文献类型：
--
作者：
Takeda, Masaya;Otsuka, Fumio;Takahashi, Hiroaki;Inagaki, Kenichi;Miyoshi, Tomoko;Tsukamoto, Naoko;Makino, Hirofumi;Lawson, Mark A.
关键词：
已知骨形态发生蛋白(BMPs)调节垂体促性腺激素的转录和产生。然而，BMPs在促性腺激素释放激素(GnRH)诱导的FSH产生中的作用仍不确定。在这里，我们使用小鼠促性腺激素LβT2细胞，描述了骨形态发生蛋白-6和骨形态发生蛋白-7信号与促性腺激素释放激素诱导的促性腺激素转录活性之间的功能联系。在LβT2细胞中，BMP-6和BMP-7以浓度依赖的方式增强小鼠β启动子的活性。ActRII胞外区可抑制BMP-6和BMP-7的诱导，但不能抑制BMPRII的诱导。这些结果提示，II型受体ActRII参与了骨形态发生蛋白诱导的促卵泡激素β转录调控。值得注意的是，骨形态发生蛋白-6，而不是骨形态发生蛋白-7，提高了促性腺激素释放激素诱导的卵泡刺激素β启动子活性在LβT2细胞。由于促性腺激素释放激素能刺激LβT2细胞中丝裂原活化蛋白激酶的磷酸化，因此我们研究了丝裂原活化蛋白激酶与卵泡刺激素β转录之间的功能联系。抑制ERK信号通路可抑制促性腺激素释放激素诱导的卵泡刺激素β转录，但不能抑制p38或SAPK/JNK信号通路，提示ERK参与了促性腺激素释放激素诱导的卵泡刺激素β转录。与骨形态发生蛋白-7共同作用，但不与骨形态发生蛋白-6共同作用，抑制促性腺激素释放激素诱导的LβT2细胞中丝裂原活化蛋白激酶的磷酸化。因此，骨形态发生蛋白-6和骨形态发生蛋白-7在促进促性腺激素释放激素诱导的促性腺激素释放激素β转录方面的差异可能是由于骨形态发生蛋白配体在促性腺激素释放激素信号转导中的不同作用。另一方面，GnRH降低Smad1/5/8的磷酸化，增加Smad6/7的表达。这些发现暗示GnRH作用、MAPK信号和垂体促性腺激素中的BMP系统之间存在功能联系，以微调FSH基因的表达。
It is known that bone morphogenetic proteins (BMPs) regulate gonadotropin transcription and production by pituitary gonadotrope cells. However, the role of BMPs in gonadotropin-releasing hormone (GnRH)-induced FSH production remains uncertain. Here, we describe a functional link between BMP-6 and BMP-7 signals and FSH transcriptional activity induced by GnRH using mouse gonadotrope LβT2 cells. In LβT2 cells, BMP-6 and BMP-7 increased mouse FSHβ-promoter activity in a concentration-dependent manner. The induction by BMP-6 and BMP-7 was inhibited by treatment with extracellular domains of ActRII but not BMPRII. These findings suggest that the type II receptor ActRII participates in BMP-induced FSHβ transcription regulation. Notably, BMP-6, but not BMP-7, enhanced GnRH-induced FSHβ-promoter activity in LβT2 cells. Since GnRH stimulated MAPK phosphorylation in LβT2 cells, a functional link between MAPK and FSHβ transcription was examined. Inhibition of the ERK pathway, but not that of p38 or SAPK/JNK signaling, suppressed GnRH-induced FSHβ transcription, suggesting that ERK is functionally involved in GnRH-induced FSHβ transcription. Co-treatment with BMP-7, but not with BMP-6, suppressed GnRH-induced MAPK phosphorylation in LβT2 cells. Thus, the difference between BMP-6 and BMP-7 in enhancing GnRH-induced FSHβ transcription may be due to the differential effects of BMP ligands on GnRH-induced ERK signaling. On the other hand, GnRH reduced Smad1/5/8 phosphorylation but increased Smad6/7 expression. These findings imply the presence of a functional link between GnRH action, MAPK signaling and the BMP system in pituitary gonadotropes for fine-tuning of FSH gene expression.
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影响因子：
4.8
作者：
Otsuka, F;Yamamoto, S;Shimasaki, S
通讯作者：
Shimasaki, S
影响因子：
--
作者：
Sosnowski, R;Mellon, PL;Lawson, MA
通讯作者：
Lawson, MA
影响因子：
4
作者：
Miyoshi, Tomoko;Otsuka, Fumio;Makino, Hirofumi
通讯作者：
Makino, Hirofumi
影响因子：
4
作者：
Sallon, C.;Faure, M. O.;Taragnat, C.
通讯作者：
Taragnat, C.
影响因子：
4.8
作者：
McMahon, Heather E.;Hashimoto, Osamu;Shimasaki, Shunichi
通讯作者：
Shimasaki, Shunichi