Nillni E A
Department of Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
Endocrine. 1999 Jun;10(3):185-99. doi: 10.1007/BF02738618.
This review presents an overview of the current knowledge on proTRH biosynthesis, its processing, its tissue distribution, and the role of known processing enzymes in proTRH maturation. The neuroendocrine regulation of TRH biosynthesis, the biological actions of its products, and the signal transduction and catabolic pathways used by those products are also reviewed. The widespread expression of proTRH, PC1, and PC2 rnRNAs in hypophysiotropic and extrahypophysiotropic areas of the brain, with their overlapping distribution in many areas, indicates the striking versatility provided by tissue-specific processing in generating quantitative and qualitative differences in nonTRH peptide products as well as TRH. Evidence is presented suggesting that differential processing for proTRH at the intracellular level is physiologically relevant. It is clear that control over the diverse range of proTRH-derived peptides within a specific cell is accomplished most from the regulation at the posttranslational level rather than the translational or transcriptional levels. Several examples supporting this hypothesis are presented in this review. A better understanding of proTRH-derived peptides role represents an exciting new frontier in proTRH research. These connecting sequences in between TRH molecules to form the precursor protein may function as structural or targeting elements that guide the folding and sorting of proTRH and its larger intermediates so that subsequent processing and secretion are properly regulated. The particular anatomical distribution of the proTRH end products, as well as regulation of their levels by neuroendocrine or pharmacological manipulations, supports a unique potential biologic role for these peptides.
本综述概述了目前关于促甲状腺激素释放激素原（proTRH）生物合成、加工、组织分布以及已知加工酶在proTRH成熟过程中作用的知识。还综述了TRH生物合成的神经内分泌调节、其产物的生物学作用以及这些产物所使用的信号转导和分解代谢途径。proTRH、PC1和PC2 mRNA在脑促垂体区和脑外促垂体区广泛表达，且在许多区域分布重叠，这表明组织特异性加工在产生非TRH肽产物以及TRH的数量和质量差异方面具有显著的多功能性。有证据表明，proTRH在细胞内水平的差异加工具有生理相关性。显然，对特定细胞内多种proTRH衍生肽的控制主要是通过翻译后水平的调节而非翻译或转录水平来实现的。本综述给出了几个支持这一假说的例子。更好地理解proTRH衍生肽的作用代表了proTRH研究中一个令人兴奋的新领域。TRH分子之间形成前体蛋白的这些连接序列可能作为结构或靶向元件，指导proTRH及其较大中间体的折叠和分选，从而使后续的加工和分泌得到适当调节。proTRH终产物的特定解剖分布以及神经内分泌或药理学操作对其水平的调节，支持了这些肽具有独特的潜在生物学作用。
