Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons.
Dihydrotestosterone activates CREB signaling in cultured hippocampal neurons.
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DOI：
10.1016/j.brainres.2009.08.066
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发表时间：
2009-11-17
期刊：
影响因子：
2.9
通讯作者：
Pike CJ
中科院分区：
文献类型：
--
作者：
Nguyen TV;Yao M;Pike CJ
虽然雄激素在大脑中诱导了许多活动，但对于雄激素在神经元中激活了哪些细胞信号通路却知之甚少。我们实验室最近的工作表明，雄激素睾酮和二氢睾酮（DHT）激活雄激素受体（AR）依赖性丝裂原激活蛋白激酶/细胞外信号调节激酶（MAPK/ERK）信号。由于转录因子环AMP反应元件结合蛋白（CREB）是MAPK/ERK的下游效应因子，雄激素在非神经元细胞中激活和激活CREB，我们研究了雄激素是否激活神经元中的CREB信号。首先，我们观察到DHT在培养的海马神经元中迅速激活CREB， CREB磷酸化证明了这一点。此外，我们观察到dht诱导的CREB磷酸化是AR依赖性的，因为它发生在稳定转染了AR的PC12细胞中，而在野生型和空载体转染的细胞中都没有发生。接下来，我们试图利用药物抑制剂确定CREB磷酸化上游的信号转导途径。DHT诱导的神经元CREB磷酸化依赖于蛋白激酶C （PKC）信号，但不依赖于MAPK/ERK、磷脂酰肌醇3-激酶、蛋白激酶A和Ca2+/钙调素依赖性蛋白激酶IV。这些结果表明DHT诱导PKC依赖性CREB信号，这可能有助于雄激素介导的神经功能。
Although androgens induce numerous actions in brain, relatively little is known about which cell signaling pathways androgens activate in neurons. Recent work in our laboratory showed that the androgens testosterone and dihydrotestosterone (DHT) activate androgen receptor (AR)-dependent mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling. Since the transcription factor cyclic AMP response element binding protein (CREB) is a downstream effector of MAPK/ERK and androgens activate and CREB in non-neuronal cells, we investigated whether androgens activate CREB signaling in neurons. First, we observed that DHT rapidly activates CREB in cultured hippocampal neurons, as evidenced by CREB phosphorylation. Further, we observed that DHT-induced CREB phosphorylation is AR-dependent, as it occurs in PC12 cells stably transfected with AR but in neither wild-type nor empty vector-transfected cells. Next, we sought to identify the signal transduction pathways upstream of CREB phosphorylation using pharmacological inhibitors. DHT-induced CREB phosphorylation in neurons was found to be dependent upon protein kinase C (PKC) signaling but independent of MAPK/ERK, phosphatidylinositol 3-kinase, protein kinase A, and Ca2+/calmodulin-dependent protein kinase IV. These results demonstrate that DHT induces PKC-dependent CREB signaling, which may contribute to androgen-mediated neural functions.
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DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
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10.1073/pnas.0404278101
发表时间：
2004-07-27
影响因子：
11.1
作者：
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DOI：
10.1073/pnas.95.5.2313
发表时间：
1998-03-03
影响因子：
11.1
作者：
Crino, P;Khodakhah, K;Eberwine, J
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Eberwine, J