Tanycytes, glial-like cells that line the third ventricle, are emerging as components of the hypothalamic networks that control body weight and energy balance. They contact the cerebrospinal fluid (CSF) and send processes that come into close contact with neurons in the arcuate and ventromedial hypothalamic nuclei. Tanycytes are glucosensitive and are able to respond to transmitters associated with arousal and the drive to feed. At least some tanycytes are stem cells and, in the median eminence, may be stimulated by diet to generate new neurons. The quest is on to understand how tanycytes detect and respond to changes in energy balance and how they communicate with the rest of the nervous system to effect their functions.

In seasonal breeders, reproduction is synchronized to seasons by day length via the pineal hormone melatonin. Recently, we have demonstrated that Kiss1, a key activator of the reproductive function, is down-regulated in sexually inactive hamsters maintained in inhibitory short days (SDs). In rodents, Kiss1 is expressed in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus (ARC). Because both the duration of the nocturnal peak of melatonin and circulating sex steroid levels vary with photoperiod, the aim of this study was to determine whether melatonin and sex steroids differentially regulate Kiss1 expression in the ARC and the AVPV. Kiss1 expression was examined by in situ hybridization in both male and female hamsters kept in various experimental conditions, and we observed that 1) SD exposure markedly reduced Kiss1 expression in the ARC and AVPV of male and female hamsters as compared to LD animals, 2) sex steroid treatment in SD-adapted male and female hamsters increased the number of Kiss1 neurons in the AVPV but decreased it in the ARC, 3) melatonin administration to LD-adapted hamsters decreased Kiss1 mRNA level in both the AVPV and the ARC in intact animals, whereas in castrated hamsters, melatonin rapidly inhibited Kiss1 expression in the ARC but not in the AVPV, and 4) pinealectomy of male or female SD-adapted hamsters increased the number of Kiss1 neurons in the ARC but not in the AVPV. In conclusion, our data demonstrate that Kiss1 expression in the Syrian hamster hypothalamus is down-regulated in SD via different mechanisms. In the ARC, melatonin inhibits Kiss1 via a direct effect on the hypothalamus, and this effect is probably sex steroid dependent, whereas in the AVPV, the decrease in Kiss1 expression appears to be secondary to the melatonin-driven reduction of sex steroid levels. Taken together, our data support the hypothesis that ARC Kiss1 neurons mediate melatonin effects on the gonadotropic axis of the Syrian hamster.

:  Seasonal mammals typically of temperate or boreal habitats use the predictable annual cycle of daylength to initiate a suite of physiological and behavioural changes in anticipation of adverse environmental winter conditions, unfavourable for survival and reproduction. Daylength is encoded as the duration of production of the pineal hormone melatonin, but how the melatonin signal is decoded has been elusive. From the studies carried out in birds and mammals together with the advent of technologies such as microarray analysis of gene expression, progress has been achieved to demystify how seasonal physiology is regulated in response to the duration of melatonin signalling. The critical tissue for the action of melatonin is the pars tuberalis (PT) where melatonin receptors are located. At the molecular level, regulation of cyclic adenosine monophosphate (cAMP) signalling in this tissue is likely to be a key event for melatonin action, either an acute inhibitory action or sensitization of this pathway by prolonged stimulation of melatonin receptors reflecting durational melatonin presence. Melatonin action at the PT has been shown to have both positive and negative effects on gene transcription, incorporating components of the circadian clock as part of the mechanism of decoding the melatonin signal and regulating thyrotrophin‐stimulating hormone (TSH) expression, a key output hormone of the PT. Microarray analysis of gene expression of PT tissue exposed to long and short photoperiods has identified important new genes that may be regulated by melatonin and contributing to the seasonal regulation of TSH production by this tissue. In the brain, tanycytes lining the third ventricle of the hypothalamus and regulation of thyroid hormone synthesis by PT‐derived TSH in these cells are now established as an important component of the pathway leading to seasonal changes in physiology. Beyond the tanycyte, identified changes in gene expression for neuropeptides, receptors and other signalling molecules pinpoint some of the areas of the brain, the hypothalamus in particular, that are likely to be involved in the regulation of seasonal physiology.

Hypothalamic tanycytes are glial‐like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor‐dependent mechanism. Here, we show that tanycytes in rodents respond to non‐nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor. The initial sweet tastant‐evoked response, which requires the presence of extracellular Ca2+, leads to release of ATP and a larger propagating Ca2+ response mediated by P2Y1 receptors. In Tas1r2 null mice the proportion of glucose nonresponsive tanycytes was greatly increased in these mice, but a subset of tanycytes retained an undiminished sensitivity to glucose. Our data demonstrate that the sweet taste receptor mediates glucosensing in about 60% of glucosensitive tanycytes while the remaining 40% of glucosensitive tanycytes use some other, as yet unknown mechanism.