Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin.
Interaction of pituitary hormones and expression of clock genes modulated by bone morphogenetic protein-4 and melatonin.
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DOI：
10.1016/j.bbrc.2015.02.100
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Naoko Tsukamoto-Yamauchi;T. Terasaka;Y. Iwasaki;F. Otsuka
中科院分区：
文献类型：
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作者：
Naoko Tsukamoto-Yamauchi;T. Terasaka;Y. Iwasaki;F. Otsuka
通过研究垂体前叶细胞中骨形态发生蛋白（BMP）-4和褪黑激素的作用，研究了生物钟基因和垂体激素的功能相互作用。阿黑皮素原（POMC）和Per 2的mRNA表达之间的显着相关性被揭示在系列培养的促肾上腺皮质激素AtT 20细胞。在AtT 20细胞中通过siRNA敲低Per 2表达导致POMC mRNA水平显著降低，有或没有促肾上腺皮质激素释放激素（CRH）刺激。BMP-4和褪黑激素均可抑制POMC表达，用这两种药物处理可降低AtT 20细胞中Per 2 mRNA和蛋白质水平。另一方面，在催乳素GH 3细胞中，发现催乳素（PRL）和时钟mRNA水平之间的表达相关性，在毛喉素处理的存在下减弱。siRNA介导的Clock表达的敲低，而不是Bmal 1的敲低，显著降低了GH 3细胞中的PRL mRNA水平。有趣的是，时钟mRNA和蛋白质水平并没有波动与褪黑激素，BMP-4或毛喉素治疗，虽然Bmal 1的表达显着增加毛喉素治疗。总的来说，POMC和Per 2的表达之间的显着相关性和PRL和时钟之间的发现分别在促皮质激素细胞和催乳激素细胞。Per 2的表达被包括褪黑激素和BMP-4在内的POMC调节剂抑制，而Clock的表达稳定地维持。因此，褪黑激素和BMP-4对时钟基因表达的影响可能意味着垂体前叶分泌的促肾上腺皮质激素（ACTH）和PRL的昼夜节律的差异稳定性。
Functional interaction of clock genes and pituitary hormones was investigated by focusing on bone morphogenetic protein (BMP)-4 and melatonin actions in anterior pituitary cells. A significant correlation between the mRNA expression of proopiomelanocortin (POMC) and Per2 was revealed in serial cultures of corticotrope AtT20 cells. Knockdown of Per2 expression by siRNA in AtT20 cells resulted in a significant reduction of POMC mRNA level with or without corticotropin-releasing hormone (CRH) stimulation. Treatments with BMP-4 and melatonin, both of which suppress POMC expression, reduced Per2 mRNA as well as protein levels in AtT20 cells. On the other hand, in lactosomatotrope GH3 cells, an expressional correlation was found between prolactin (PRL) and Clock mRNA levels, which was attenuated in the presence of forskolin treatment. The siRNA-mediated knockdown of Clock expression, but not that of Bmal1, significantly reduced PRL mRNA levels in GH3 cells. Interestingly, Clock mRNA and protein levels did not fluctuate with melatonin, BMP-4 or forskolin treatment, although Bmal1 expression was significantly increased by forskolin treatment. Collectively, a significant correlation between the expression of POMC and Per2 and that between PRL and Clock were uncovered in corticotrope and lactosomatotrope cells, respectively. Per2 expression was inhibited by POMC modulators including melatonin and BMP-4, while Clock expression was steadily maintained. Thus, the effects of melatonin and BMP-4 on clock gene expression may imply differential stability of circadian rhythms of adrenocorticotropin (ACTH) and PRL secreted from the anterior pituitary.