Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes.
Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes.
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DOI：
10.3389/fendo.2016.00024
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发表时间：
2016
影响因子：
5.2
通讯作者：
Lalli E
中科院分区：
文献类型：
--
作者：
Ruggiero C;Lalli E
促肾上腺皮质激素（ACTH）通过激活cAMP/蛋白激酶a （PKA）信号，刺激类固醇激素的生物合成，引起快速、急性和长期、慢性反应。急性反应是由胆固醇从脂质储存中动员并将其运送到线粒体内膜开始的，这一过程是由类固醇急性调节蛋白介导的。慢性反应导致编码类固醇生成酶的基因的协调转录增加。ACTH与其同源受体黑素皮质素2受体（melanocortin 2 receptor, MC2R）结合，刺激腺苷酸环化酶，从而诱导cAMP的产生、PKA的激活和特定核因子的磷酸化，这些核因子与靶启动子结合，促进辅激活子蛋白的募集，从而指导类固醇基因的转录。本文综述了ACTH/cAMP系统对肾上腺皮质甾体生成酶编码基因表达的转录调控作用。特别强调将给予所需的转录因子介导促肾上腺皮质激素依赖性转录类固醇基因。
The trophic peptide hormone adrenocorticotropic (ACTH) stimulates steroid hormone biosynthesis evoking both a rapid, acute response and a long-term, chronic response, via the activation of cAMP/protein kinase A (PKA) signaling. The acute response is initiated by the mobilization of cholesterol from lipid stores and its delivery to the inner mitochondrial membrane, a process that is mediated by the steroidogenic acute regulatory protein. The chronic response results in the increased coordinated transcription of genes encoding steroidogenic enzymes. ACTH binding to its cognate receptor, melanocortin 2 receptor (MC2R), stimulates adenylyl cyclase, thus inducing cAMP production, PKA activation, and phosphorylation of specific nuclear factors, which bind to target promoters and facilitate coactivator protein recruitment to direct steroidogenic gene transcription. This review provides a general view of the transcriptional control exerted by the ACTH/cAMP system on the expression of genes encoding for steroidogenic enzymes in the adrenal cortex. Special emphasis will be given to the transcription factors required to mediate ACTH-dependent transcription of steroidogenic genes.