Photoperiod-dependent proteolytic processing of neuropeptide precursors

Body weight in seasonal animals such as the Siberian hamster (Phodopus sungorus) is regulated by a complex interaction of neuropeptides in a hypothalamic network of neurons that integrates environmental photoperiod inputs. Most of these energy balance-regulating neuropeptides derive from larger biol...

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Bibliographic Details
Main Author: Helwig, Michael
Contributors: Klingenspor, Martin (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:English
Published: Philipps-Universität Marburg 2008
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Summary:Body weight in seasonal animals such as the Siberian hamster (Phodopus sungorus) is regulated by a complex interaction of neuropeptides in a hypothalamic network of neurons that integrates environmental photoperiod inputs. Most of these energy balance-regulating neuropeptides derive from larger biologically inactive precursors and have to undergo post-translational processing by endo- and exoproteolytic cleavage. In the current PhD thesis we investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3), 2 (PC2), carboxypeptidase D and E (CPD and CPE) and the proteolytic processing of the neuropeptide precursor pro-opiomelanocortin (POMC) within key energy balance regulating centres of the hypothalamus. We compared mRNA levels and protein distribution of the enzymes PC1/3, PC2, CPD and CPE and the neuropeptide precursor POMC and its derived peptides ACTH, a-MSH and ß-endorphin in selected hypothalamic areas of either long day (LD, 16h light: 8h dark) or short day (SD, 8h light: 16h dark) acclimated Siberian hamsters. Messenger RNA and immunoreactivity of PC1/3 enzyme and neuropeptides cleaved by PC1/3 such as ACTH in the ARC, and orexin A in the LH, were not affected by photoperiod changes. In contrast increased levels of PC2 mRNA and protein were associated with a higher abundance of the mature neuropeptides a-MSH and ß-endorphin in SD. CPE immunoreactivity was increased in SD and after leptin injection suggesting increased terminal activation of neuropeptides subsequent to processing by PC2. The photoperiod-driven regulatory mechanism by differential activity of the major neuroendocrine enzymes on a posttranslational level observed in this study could be an additional universal control point for selective maturation of energy balance related neuropeptides.
DOI:10.17192/z2008.0490