Retinoic acid regulates growth-related gene expression in the rat hypothalamus
P. Stoney, P. Morgan & P. McCaffery
The vitamin A-derived hormone retinoic acid (RA) is best known for its essential role in development, but components of the RA signalling pathway are also expressed in regions of the adult brain, including the hypothalamus, which regulates feeding behaviour, metabolism and body weight. RA is synthesised by the tanycytes lining the third ventricle and has recently been found to regulate cell proliferation in the hypothalamus. Some animals, such as the hamster and F344 rat, alter their feeding and body weight in response to changes in day length and photoperiod manipulation is a useful system for investigating growth- and weight-related changes in the hypothalamus. Expression of the RA synthetic enzyme retinaldehyde dehydrogenase 1 (RALDH1) is photoperiodically regulated in the hypothalamus of the photoresponsive F344 rat, with higher RALDH1 expression in rats kept on a long-day photoperiod (16 h light:8 h darkness; LD), relative to short-day (8 h light:16 h darkness; S.D.). This suggests that RA levels are higher, and RA signalling more active, under LD conditions. To further investigate the role of RA signalling, hypothalamic slices from P10 male Sprague-Dawley rats were cultured in the absence of vitamin A for 4 days, then treated for 48 h with either DMSO or 10−6 M RA. qPCR analysis of treated tissue showed that RA treatment increased hypothalamic expression of GHRH, AGRP and POMC, genes known to be upregulated in LD-exposed rats. PCSK2, which encodes a prohormone convertase necessary for posttranslational processing of POMC, was also upregulated by RA. NPY and CART, genes associated with SD photoperiod, were unaffected by RA treatment. These results demonstrate that increasing hypothalamic RA levels is sufficient to upregulate genes associated with LD photoperiod and suggest that RA signalling contributes to the control of body weight by regulating the expression of growth-promoting genes in the hypothalamus.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.