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Photoperiodic Regulation of Hypothalamic Retinoid Signaling: Association of Retinoid X Receptor with Body Weight

Molecular Endocrinology Group (A.W.R., C.A.W., J.G.M., K.M.M., P.B., P.J.M.), Rowett Research Institute, Aberdeen, AB21 9SB, Scotland, United Kingdom; and School of Biomedical Sciences (F.J.E., S.S.), University of Nottingham Medical School, Nottingham, NG7 2UH, United Kingdom

Address all correspondence and requests for reprints to: Professor Peter J. Morgan, Institute Director, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, United Kingdom. E-mail: p.morgan{at}rowett.ac.uk.

This study reports novel events related to photoperiodic programming of the neuroendocrine hypothalamus. To investigate photoperiod-responsive genes, Siberian hamsters were maintained in long or short photoperiods that generate physiological states of obesity or leanness. Microarray expression analysis first identified CRBP1 as a photoperiod-responsive gene, and then further studies using in situ hybridization and immunocytochemistry revealed that expression levels of several related retinoid-signaling genes were modulated in response to photoperiod changes. Genes of the retinoid-signaling pathway, encoding nuclear receptors (RXR/RAR) and retinoid binding proteins (CRBP1 and CRABP2) are photoperiodically regulated in the dorsal tuberomamillary nucleus (DTM): Their expression is significantly lower in short photoperiods and parallels body weight decreases. Studies in pinealectomized hamsters confirm that the pineal melatonin rhythm is necessary for these seasonal changes, and studies in testosterone-treated hamsters reveal that these changes in gene expression are not the secondary consequence of photoperiod-induced changes in steroid levels. Comparative studies using Syrian hamsters, which show divergent seasonal body weight responses to Siberian hamsters when exposed to short photoperiods, showed a distinct pattern of changes in retinoid gene expression in the DTM in response to a change in photoperiod. We infer that the DTM may be an important integrating center for photoperiodic control of seasonal physiology and suggest that the changes in retinoid X receptor expression may be associated with seasonal changes in body weight and energy metabolism.

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