IMR Press / FBL / Volume 12 / Issue 9 / DOI: 10.2741/2334

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

The biosynthesis and processing of neuropeptides: lessons from prothyrotropin releasing hormone (proTRH)
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1 Division of Endocrinology, Department of Medicine, Brown Medical School, Rhode Island Hospital, Providence, RI, USA
2 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University,Providence, RI, USA
Front. Biosci. (Landmark Ed) 2007, 12(9), 3554–3565;
Published: 1 May 2007

The biosynthesis of prohormone-derived peptides is a complex cellular process, which requires specific cleavage, sorting, and modifications of the peptides before the final generation of the bioactive products. In this review, we describe the current knowledge of the cell biology of a key prohormone: proThyrotropin Releasing Hormone (proTRH), which is the precursor of the TRH peptide. In particular, we focus on the biosynthesis of the hypophysiotropic TRH, which is produced in the hypothalamic paraventricular nucleus (PVN) and is the main activator of the hypothalamic-pituitary-thyroid (HPT) axis. Recently, we showed that the regulation of the biosynthesis of TRH in the PVN also occurs at post-translational level through coordinated changes in proTRH processing, by the action of the prohormone convertase (PC1/3 and PC2) processing enzymes. Such regulation, which represents a novel aspect in the regulation of the neuropeptide biosynthesis, ultimately would lead to a more effective processing of prohormones into mature peptides.

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