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Melatonin Regulates Type 2 Deiodinase Gene Expression in the Syrian Hamster

Département de Neurobiologie des Rythmes (F.G.R., M.S., P.P., V.S.), Centre National de la Recherche Scientifique Unité Mixte de Recherche-7168/LC2, Institut des Neurosciences Cellulaires et Intégratives, Université Louis Pasteur-IFR des Neurosciences, 67084 Strasbourg Cedex, France; and Department of Functional Neuroanatomy and Biomarkers (F.G.R., J.D.M.), NeuroSearch A/S, DK-2750 Ballerup, Denmark

Address all correspondence and requests for reprints to: Valérie Simonneaux, Département de Neurobiologie des Rythmes, Centre National de la Recherche Scientifique Unité Mixte de Recherche-7168/LC2, Institut des Neurosciences Cellulaires et Intégratives, Université Louis Pasteur-Institut Fédératif de Recherche des Neurosciences, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France. E-mail: simonneaux{at}neurochem.u-strasbg.fr.

In seasonal species, photoperiod organizes various physiological processes, including reproduction. Recent data indicate that the expression of type 2 iodothyronine deiodinase (Dio2) is modulated by photoperiod in the mediobasal hypothalamus of some seasonal species. Dio2 is believed to control the local synthesis of bioactive T₃ to regulate gonadal response. Here we used in situ hybridization to study Dio2 expression in the hypothalamus of a photoperiodic rodent, the Syrian hamster. Dio2 was highly expressed in reproductively active hamsters in long day, whereas it was dramatically reduced in sexually inhibited hamsters maintained in short day. This contrasted with the laboratory rat, a nonphotoperiodic species, in which no evidence for Dio2 photoperiodic modulation was seen. We also demonstrate that photoperiodic variations of Dio2 expression in hamsters are independent from secondary changes in gonadal steroids. Studies in pinealectomized hamsters showed that the photoperiodic variation of Dio2 expression is melatonin dependent, and injections of long day hamsters with melatonin for only 7 d were sufficient to inhibit Dio2 expression to that of short day levels. Finally, because in some seasonal species thyroid hormones are involved in photorefractoriness, we examined Dio2 expression in short day-refractory hamsters and found that Dio2 mRNA levels remained low despite full reproductive recrudescence. Altogether, these results demonstrate that in the Syrian hamster Dio2 is photoperiodically modulated via a melatonin-dependent process. Furthermore, refractoriness to photoperiod in hamsters appears to occur independently of Dio2. These results raise new perspectives for understanding how thyroid hormones are involved in the control of photoperiodic neuroendocrine processes.

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