Cawley Niamh X, Li Zhaojin, Loh Y Peng
Section on Cellular NeurobiologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Section on Cellular NeurobiologyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
J Mol Endocrinol. 2016 May;56(4):T77-97. doi: 10.1530/JME-15-0323. Epub 2016 Feb 15.
Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide hormones within its structure. These peptide hormones can be generated by cleavage of POMC at basic residue cleavage sites by prohormone-converting enzymes in the regulated secretory pathway (RSP) of POMC-synthesizing endocrine cells and neurons. The peptides are stored inside the cells in dense-core secretory granules until released in a stimulus-dependent manner. The complexity of the regulation of the biosynthesis, trafficking, and secretion of POMC and its peptides reflects an impressive level of control over many factors involved in the ultimate role of POMC-expressing cells, that is, to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to adrenocorticotropic hormone (ACTH) and β-lipotropin in the late 1970s to our current knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology. In this article, we describe the intracellular trafficking of POMC in endocrine cells, its sorting into dense-core secretory granules and transport of these granules to the RSP. Additionally, we review the enzymes involved in the maturation of POMC to its various peptides and the mechanisms involved in the differential processing of POMC in different cell types. Finally, we highlight studies pertaining to the regulation of ACTH secretion in the anterior and intermediate pituitary and POMC neurons of the hypothalamus.
阿黑皮素原（POMC）是一种前体激素，其结构中编码多种较小的肽类激素。这些肽类激素可通过POMC合成内分泌细胞和神经元的调节性分泌途径（RSP）中的前体激素转化酶，在碱性残基裂解位点切割POMC而产生。这些肽储存在细胞内的致密核心分泌颗粒中，直到以刺激依赖的方式释放。POMC及其肽的生物合成、运输和分泌的调节复杂性反映了对参与POMC表达细胞最终作用的许多因素的高度控制，也就是说，当身体发出信号时，产生一系列不同的具有生物活性的肽类激素以备行动。从20世纪70年代末发现POMC是促肾上腺皮质激素（ACTH）和β-促脂素的前体到我们目前的认识，对POMC生理学的理解仍然是一项具有里程碑意义的工作，为分子内分泌学的许多方面提供了见解。在本文中，我们描述了POMC在内分泌细胞中的细胞内运输、其分选到致密核心分泌颗粒以及这些颗粒向RSP的运输。此外，我们回顾了参与POMC成熟为其各种肽的酶以及不同细胞类型中POMC差异加工所涉及的机制。最后，我们重点介绍了与垂体前叶和中间叶以及下丘脑POMC神经元中ACTH分泌调节相关的研究。
