VGF derived peptides, TLQP-21 and HHPD-41, appear to have opposite effects on food intake in Siberian hamsters (Jethwa et al., 2007; Lewis et al., unpublished data). VGF mRNA expression is altered by photoperiod in Siberian hamsters, with increased levels observed in the dorsal medial arcuate nucleus of the hypothalamus in the short photoperiod (SD) (Barrett et al., 2005), when food intake is reduced.  It has recently been postulated that hypothalamic thyroid hormone availability plays a key role in the seasonal regulation of appetite and bodyweight, since a reduction in the local availability of tri-iodothyronine (T₃) in SD results in hypophagia and weight loss (Murphy et al., 2012).  Therefore, using the SH-SY5Y cell line as an in vitro model, we investigated whether T₃ affects endogenous expression of VGF and VGF promoter activity as a mechanism for the observed decrease in VGF expression in SD.  Initial studies showed that 10nM T₃ reduced endogenous VGF gene expression (p < 0.001) 24 hours post addition in SH-SY5Y cells.  A reporter construct, based on the mammalian expression vector, pZsGreen1, was designed containing 1Kb of the VGF promoter, including a postulated T3 response element (TRE).  As hypothesised, T₃ (both 5 and 10nM) reduced VGF promoter activities after 2, 6, 24 and 48hrs of treatment (p < 0.001), while truncation of the promoter region to remove the TRE nullified the effect of T₃ on VGF promoter activity.  In conclusion, we have identified a possible mechanism whereby T₃ and VGF appear to interact in the seasonal regulation of appetite.