Reproduction, Mother and Child Health, Centre de recherche du CHU de Québec-Université Laval, Québec, Quebec, Canada.
Centre de recherche en reproduction, développement et santé intergénérationnelle, Department of Obstetrics, Gynecology, and Reproduction, Université Laval, Québec, Quebec, Canada.
J Endocrinol. 2024 Oct 8;263(2). doi: 10.1530/JOE-24-0087. Print 2024 Nov 1.
The steroidogenic acute regulatory (STAR) protein is an essential cholesterol transporter that shuttles cholesterol from the outer to the inner mitochondrial membrane in the major steroidogenic endocrine organs. It is a key player in the acute regulation of steroid hormone biosynthesis in response to tropic hormone stimulation. Its discovery 30 years ago sparked immediate interest in understanding how STAR action is controlled. Since increased STAR gene expression is a classic feature of the acute regulation of steroidogenesis, a special emphasis was placed on defining the transcriptional regulatory mechanisms that underlie its rapid induction in response to tropic hormone stimulation. These mechanisms include the effects of enhancers, the regulation of chromatin accessibility, the impact of epigenetic factors, and the role of transcription factors. Over the past three decades, understanding the transcription factors that regulate STAR gene expression has been the subject of more than 170 independent scientific publications, making it one of, and if not the best, studied genes in the steroidogenic pathway. This intense research effort has led to the identification of dozens of transcription factors and their related binding sites in STAR 5' flanking (promoter) sequences across multiple species. STAR gene transcription appears to be complex in that a large number of transcription factors have been proposed to interact with either isolated or overlapping regulatory sequences that are tightly clustered over a relatively short promoter region upstream of the STAR transcription start site. Many of these transcription factors appear to work in unique combinatorial codes and are impacted by diverse hormonal and intracellular signaling pathways. This review provides a retrospective overview of the transcription factors proposed to regulate both basal and acute (hormonal) STAR gene expression, and how insights in this area have evolved over the past 30 years.
类固醇生成急性调节蛋白（STAR）是一种必需的胆固醇转运蛋白，它将胆固醇从细胞器外膜转运到主要类固醇生成内分泌器官的内膜。它是激素刺激下类固醇激素生物合成急性调节的关键因子。它的发现引发了人们对理解 STAR 作用如何被调控的浓厚兴趣。由于 STAR 基因表达的增加是类固醇生成急性调节的经典特征，因此特别强调定义其快速诱导的转录调控机制，这些机制包括增强子的作用、染色质可及性的调节、表观遗传因素的影响以及转录因子的作用。在过去的三十年中，理解调控 STAR 基因表达的转录因子一直是 170 多篇独立科学出版物的主题，使其成为类固醇生成途径中研究最多的基因之一，如果不是最多的话。这项深入的研究工作导致了数十种转录因子及其在多种物种中 STAR5'侧翼（启动子）序列中的相关结合位点的鉴定。STAR 基因转录似乎很复杂，因为已经提出了许多转录因子与在 STAR 转录起始位点上游的相对较短的启动子区域中紧密聚集的分离或重叠的调节序列相互作用。许多这些转录因子似乎以独特的组合代码工作，并受到多种激素和细胞内信号通路的影响。这篇综述回顾了被提议调节基础和急性（激素）STAR 基因表达的转录因子，并介绍了在过去 30 年中这一领域的研究进展。
