Figure 5.

Schematic summary of the proposed photoneuroendocrine control of VGF expression. Thyroxine (T₄) is taken up from the circulation into tanycytes via MCT8 transporters, and in LD is converted by DIO2 to T₃ (Ebling 2014). Furthermore, in LD, components of the retinoic acid-signaling pathway – CRBP-1, CRABP-2, RAR, and RXR – are all upregulated in the Siberian hamster (Ross et al. 2005, Barrett et al. 2006), while RALDH-1 is increased in the photoperiodic rat (Shearer et al. 2010). We demonstrate that VGF expression and promoter activity in SH-SY5Y cells is increased in response to treatment with RA and vitamin D and reduced in response to treatment with T₃. Furthermore, VGF mRNA expression is reduced in response to intra-hypothalamic T₃ administration in the SD-exposed Siberian hamster. In SD, expression of DIO3 is upregulated, and thus, inactive metabolites of T₄ such as rT₃ and T₂ are produced alongside reductions in components of the retinoic acid-signaling pathway, while vitamin D plasma levels are increased. This may account for the increase in VGF expression in the dmpARC whilst reducing VGF expression in the ARC. Adapted from Ebling (2014).