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Hypothalamic Thyroid Hormone Catabolism Acts as a Gatekeeper for the Seasonal Control of Body Weight and Reproduction

Rowett Research Institute and Aberdeen Center for Energy Regulation and Obesity (P.B., D.W., A.W.R., D.M.O., Z.A.A., J.G.M., P.J.M.), Bucksburn, Aberdeen AB21 9SB, United Kingdom; School of Biomedical Sciences (F.J.P.E., S.S., A.W., P.J.), University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom; Department of Endocrinology, Metabolism (A.B.), F5-165, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; and Department of Internal Medicine (T.J.V.), Erasmus University Medical Center, NL-3015 GE Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Perry Barrett, Rowett Research Institute, Greenburn Road, Buckburn, Aberdeen AB21 9SB, United Kingdom. E-mail: P.Barrett{at}Rowett.ac.uk.

Seasonal adaptations in physiology exhibited by many animals involve an interface between biological timing and specific neuroendocrine systems, but the molecular basis of this interface is unknown. In this study of Siberian hamsters, we show that the availability of thyroid hormone within the hypothalamus is a key determinant of seasonal transitions. The expression of the gene encoding type III deiodinase (Dio3) and Dio3 activity in vivo (catabolism of T₄ and T₃) is dynamically and temporally regulated by photoperiod, consistent with the loss of hypothalamic T₃ concentrations under short photoperiods. Chronic replacement of T₃ in the hypothalamus of male hamsters exposed to short photoperiods, thus bypassing synthetic or catabolic deiodinase enzymes located in cells of the ependyma of the third ventricle, prevented the onset of short-day physiology: hamsters maintained a long-day body weight phenotype and failed to undergo testicular and epididymal regression. However, pelage moult to a winter coat was not affected. Type II deiodinase gene expression was not regulated by photoperiod in these hamsters. Collectively, these data point to a pivotal role for hypothalamic DIO3 and T₃ catabolism in seasonal cycles of body weight and reproduction in mammals.

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