PC1/3 and PC2 Gene Expression and Post-Translational Endoproteolytic Pro-Opiomelanocortin Processing is Regulated by Photoperiod in the Seasonal Siberian Hamster ( Phodopus sungorus ) M. Helwig,*† R. M. H. Khorooshi,‡ A. Tups,† P. Barrett,* Z. A. Archer,* C. Exner,† J. Rozman,† L. J. Braulke,† J. G. Mercer* and M. Klingenspor† *Molecular Endocrinology Group, Division of Obesity and Metabolic Health, Rowett Research Institute, Aberdeen Centre for Energy Regulation and Obesity (ACERO), Aberdeen, UK. †Department of Animal Physiology, Biology Faculty, Philipps University Marburg, Marburg, Germany. ‡Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark. Key words: seasonal body weight regulation, proteolytic processing, photoperiod, prohormone convertases, POMC. Abstract A remarkable feature of the seasonal adaptation displayed by the Siberian hamster (Phodopus sungorus) is the ability to decrease food intake and body weight (by up to 40%) in response to shortening photoperiod. The regulating neuroendocrine systems involved in this adaptation and their neuroanatomical and molecular bases are poorly understood. We investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3) and 2 (PC2) and the endoproteolytic 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 PC1/3, PC2, POMC, adrenocorticotrophic hormone (ACTH), a-melanocyte-stimulating hormone (MSH), b-endorphin and orexin-A in selected hypothalamic areas of long day (LD, 16 : 8 h light : dark), short day (SD, 8 : 16 h light : dark) and natural-day (ND, photoperiod depending on time of the year) acclimated Siberian hamsters. The gene expression of PC2 was significantly higher within the arcuate nucleus (ARC, P < 0.01) in SD and in ND (versus LD), and is reflected in the day length profile between October and April in the latter. PC1/3 gene expression in the ARC and lateral hypothalamus was higher in ND but not in SD compared to the respective LD controls. The immunoreactivity of PC1/3 cleaved neuropeptide ACTH in the ARC and PC1/3-colocalised orexin-A in the latyeral hypothalamus were not affected by photoperiod changes. However, increased levels of PC2 mRNA and protein were associated with higher abundance of the mature neuropeptides a-MSH and b-endorphin (P < 0.01) in SD. This study provides a possible explanation for previous paradoxical findings showing lower food intake in SD associated with decreased POMC mRNA levels. Our results suggest that a major part of neuroendocrine body weight control in seasonal adaptation may be effected by post-translational pro- cessing mediated by the prohormone convertases PC1/3 and PC2, in addition to regulation of gene expression of neuropeptide precursors. Seasonal animals such as the Siberian hamster (Phodopus sungorus) exhibit remarkable physiological and metabolic adaptations in response to the seasonally changing environ- ment. These adaptations include changes in coat insulation and colour, reproductive activity, food intake and body weight (1). The drive to reduce food intake in shortening winter photoperiod persists even if food is provided ad lib demonstrating the importance of this regulatory energy balance mechanism. A key neuronal centre that regulates these physiological responses is the hypothalamus, an area of the central nervous system (CNS) that integrates photoperi- odic and peripheral inputs in a complex network of interact- ing orexigenic and anorexigenic neuropeptides (2, 3). The Siberian hamster processes information on changing photo- period through the pineal hormone, melatonin, and about internal energy stores via peripherally released hormones such Correspondence to: Michael Helwig, Animal Physiology, Department of Biology, Philipps-University, Karl-von-Frisch-Str. 8, 35032 Marburg, Germany (e-mail: helwigmi@staff.uni-marburg.de). Journal of Neuroendocrinology, 2006, Vol. 18, 413–425 doi:10.1111/j.1365-2826.2006.01431.x Ó 2006 The Authors. Journal compilation Ó 2006 Blackwell Publishing Ltd