Gene expression analysis and microdialysis suggest hypothalamic triiodothyronine (T3) gates daily torpor in Djungarian hamsters (Phodopus sungorus)

Abstract

Thyroid hormones play an important role in regulating seasonal adaptations of mammals. Several studies suggested that reduced availability of 3,3',5-triiodothyronine (T3) in the hypothalamus is required for the physiological adaptation to winter in Djungarian hamsters. We have previously shown that T3 is involved in the regulation of daily torpor, but it remains unclear, whether T3 affects torpor by central or peripheral mechanisms. To determine the effect of T3 concentrations within the hypothalamus in regulating daily torpor, we tested the hypothesis that low hypothalamic T3 metabolism would favour torpor and high T3 concentrations would not. In experiment 1 gene expression in torpid hamsters was assessed for transporters carrying thyroid hormones between cerebrospinal fluid and hypothalamic cells and for deiodinases enzymes, activating or inactivating T3 within hypothalamic cells. Gene expression analysis suggests reduced T3 in hypothalamic cells during torpor. In experiment 2, hypothalamic T3 concentrations were altered via microdialysis and torpor behaviour was continuously monitored by implanted body temperature transmitters. Increased T3 concentrations in the hypothalamus reduced expression of torpor as well as torpor bout duration and depth. Subsequent analysis of gene expression in the ependymal layer of the third ventricle showed clear up-regulation of T3 inactivating deiodinase 3 but no changes in several other genes related to photoperiodic adaptations in hamsters. Finally, serum analysis revealed that increased total T3 serum concentrations were not necessary to inhibit torpor expression. Taken together, our results are consistent with the hypothesis that T3 availability within the hypothalamus significantly contributes to the regulation of daily torpor via a central pathway.

Hypothalamic control systems show differential gene expression during spontaneous daily torpor and fasting-induced torpor in the Djungarian hamster (Phodopus sungorus)

“…The decreased Dio2 expression observed in our study suggests a reduced conversion of T4 into the active metabolite T3 and would thereby cause low T3 availability in the hypothalamus during torpor. This is in accordance with earlier studies, demonstrating that high T3 levels specifically in the hypothalamus are able to block torpor in Djungarian hamsters, whereas systemically low T3 concentrations increase torpor frequency, depth and duration [40–42]. Here, we confirm that a lowered Dio2 expression and potential decrease in local T3 availability appears to be a permissive factor for both, SDT as well as FIT in summer and winter adapted animals.…”

“…Moreover, T3 availability affects torpor behavior. Chemical inhibition of T3 production promotes torpor expression, whereas excess T3 in the periphery as well as locally in the hypothalamus, is able to prevent torpor in winter adapted animals [40–42]. …”

Gene expression profiling during hibernation in the European hamster

“…These alterations lead to reduced T3 concentrations during torpor and arousal. Two recent studies in the Djungarian hamster demonstrated that increasing peripheral 72 or intra-hypothalamic 27 T3 resulted in reduction of torpor induction and torpor bout duration and depth, confirming the pivotal role of T3 in torpor regulation and strengthening our observation of reduced T3 metabolism during torpor.…”

“…The adaptation to winter physiology, especially torpor, requires reduced availability of thyroid hormones, particularly T3 26,27,70,71 . We show here that the Dio2 enzyme (that converts T4 to T3) was decreased in central structures: hypothalamus and pituitary gland; and peripheral organs: BAT and adrenal glands, during torpor and arousal.…”

“…It is believed that melatonin effects on seasonal functions are enacted through seasonal changes in hypothalamic T3 11,26 . This likely includes hibernation, since central administration of T3 reduces daily torpor in the Siberian hamster ( Phodopus sungorus ) 27 . Rhythmic melatonin expression and other biological rhythms depend on a circadian system comprising a master clock located in the suprachiasmatic nucleus (SCN), and secondary clocks within other central and peripheral structures 28 .…”