Siberian hamsters are seasonal mammals that survive a winter climate by making adaptations in physiology and behaviour. This includes gonadal atrophy, reduced food intake and body weight. The underlying central mechanisms responsible for the physiological adaptations are not fully established but involve reducing hypothalamic tri-iodthyronine (T3) levels. Juvenile Siberian hamsters born or raised in short days (SD) respond in a similar manner, although with an inhibition of gonadal development and growth instead of reversing an established long day (LD) phenotype. Using juvenile male hamsters, the present study aimed to investigate whether the central mechanisms are similar before the establishment of the mature LD phenotype. By in situ hybridisation, we examined the response of genes involved in thyroid hormone (Dio2 and Dio3, which determine hypothalamic T3 levels) and glucose/glutamate metabolism in the ependymal layer, histamine H3 receptor and VGF as representatives of the highly responsive dorsomedial posterior arcuate nucleus (dmpARC), and somatostatin, a hypothalamic neuropeptide involved in regulating the growth axis. Differential gene expression of type 2 and type 3 deiodinase in the ependymal layer, histamine H3 receptor in the dmpARC and somatostatin in the ARC was established by the eighth day in SD. These changes are followed by alterations in glucose metabolism related genes in the ependymal layer by day 16 and increased secretogranin expression in the dmpARC by day 32. In conclusion, our data demonstrate similar but rapid and highly responsive changes in gene expression in the brain of juvenile Siberian hamsters in response to a switch from LD to SD. The data also provide a temporal definition of gene expression changes relative to physiological adaptations of body weight and testicular development and highlight the likely importance of thyroid hormone availability as an early event in the adaptation of physiology to a winter climate in juvenile Siberian hamsters.

The Siberian hamster (Phodopus sungorus) is a seasonal mammal responding to the annual cycle in photoperiod with anticipatory physiological adaptations. This includes a reduction in food intake and body weight during the autumn in anticipation of seasonally reduced food availability. In the laboratory, short-day induction of body weight loss can be reversed or prevented by voluntary exercise undertaken when a running wheel is introduced into the home cage. The mechanism by which exercise prevents or reverses body weight reduction is unknown, but one hypothesis is a reversal of short-day photoperiod induced gene expression changes in the hypothalamus that underpin body weight regulation. Alternatively, we postulate an exercise-related anabolic effect involving the growth hormone axis. To test these hypotheses we established photoperiod-running wheel experiments of 8 to 16 weeks duration assessing body weight, food intake, organ mass, lean and fat mass by magnetic resonance, circulating hormones FGF21 and insulin and hypothalamic gene expression. In response to running wheel activity, short-day housed hamsters increased body weight. Compared to short-day housed sedentary hamsters the body weight increase was accompanied by higher food intake, maintenance of tissue mass of key organs such as the liver, maintenance of lean and fat mass and hormonal profiles indicative of long day housed hamsters but there was no overall reversal of hypothalamic gene expression regulated by photoperiod. Therefore the mechanism by which activity induces body weight gain is likely to act largely independently of photoperiod regulated gene expression in the hypothalamus.

In nature Siberian hamsters utilize the decrement in day length following the summer solstice to implement physiological adaptations in anticipation of the forthcoming winter, but also exploit an intrinsic interval timer to initiate physiological recrudescence following the winter solstice. However, information is lacking on the temporal dynamics in natural photoperiod of photoperiodically regulated genes and their relationship to physiological adaptations. To address this, male Siberian hamsters born and maintained outdoors were sampled every month over the course of one year. As key elements of the response to photoperiod, thyroid hormone signalling components were assessed in the hypothalamus. From maximum around the summer solstice (late-June), Dio2 expression rapidly declined in advance of physiological adaptations. This was followed by a rapid increase in Mct8 expression (T3/T4 transport), peaking early-September before gradually declining to minimum expression by the following June. Dio3 showed a transient peak of expression beginning late-August. A recrudescence of testes and body mass occurred from mid-February, but Dio2 expression remained low until late-April of the following year, converging with the time of year when responsiveness to short-day length is re-established. Other photoperiodically regulated genes show temporal regulation, but of note is a transient peak in Gpr50 around late-July.

Djungarian hamsters (Phodopus sungorus) were exposed to artificial short days either with access to a running wheel (RW) or without. Within 6 weeks RW hamsters considerably increased their body mass, whereas controls showed the typical body mass reduction. Estimation of paired testis weights indicated a decelerated testis regression in RW hamsters. Subsequent locking of RWs for 9 weeks led to a decline in body mass of RW animals in parallel to controls. Daily torpor was almost completely missing in hamsters with initially unlocked wheels. During the final phase when RWs were again unlocked (3 weeks), body mass of exercising hamsters increased again, while controls reached the nadir in body mass. In comparison to equiponderate long-day (LD) controls the relative liver weight of RW hamsters was significantly increased unlike the relative heart weight. However, the latter tended to be higher than in sedentary LD hamsters. A growth-stimulating effect of wheel running was proven by elongated femora in exercising short-day (SD) hamsters compared to SD controls and suggested by exercise-induced elevation of body mass in a further experiment under continuous LD conditions, indicating a growth-promoting effect of wheel running independent from the photoperiod.

25The Siberian hamster (Phodopus sungorus) is a seasonal mammal, exhibiting a suite of 26 physiologically and behaviourally distinct traits dependent on the time of year and governed by 27 changes in perceived day length (photoperiod). These attributes include significant weight loss, 28 reduced food intake, gonadal atrophy, and pelage change with short day photoperiod as in winter. 29The central mechanisms driving seasonal phenotype change during winter are mediated by a 30 reduced availability of hypothalamic tri-iodothyronine (T3), but downstream mechanisms 31 responsible for physiological and behavioural changes are yet to be fully elucidated. With access 32 to a running wheel (RW) in short photoperiod, Siberian hamsters which have undergone 33 photoperiod mediated weight loss override photoperiod-drive for reduced body weight and regain 34 weight similar to a hamster held in long days. These changes occur despite retaining the majority 35 of hypothalamic gene expression profiles appropriate for short day hamsters. Utilising the 36 somatostatin agonist pasireotide, we have recently provided evidence for an involvement of the 37 growth hormone axis (GH axis) in the seasonal regulation of bodyweight. In the present study we 38 employed pasireotide to test for the possible involvement of the GH axis in running wheel induced 39 body weight regulation. Pasireotide successfully inhibited exercise stimulated growth in short day 40 hamsters and this was accompanied by altered hypothalamic gene expression of key GH axis 41 components. Our data provides support for an involvement of the GH axis in the RW response in 42Siberian hamsters. 43