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Domestic strains of canaries (Serinus canaria) variably respond to photoperiod changes and apparently stay in breeding state for extended periods. Fife Fancy canaries are supposed to be similar to the native species living at 27–39° north where photoperiod significantly changes across the year. Our birds showed reproductive cycles when exposed to light regimes mimicking the annual cycle of photoperiod. However after 6 months in short days (SD: 8L:16D), males developed large testes, as observed by X‐ray tomography, and intense singing. Switching to long days (LD: 16L:8D) did not further increase song rate nor testes size but increased song duration, number of syllables per song, and trill occurrence frequency. No sign of regression was observed after 12 weeks in LD but return to SD produced a rapid decrease in testes size and singing activity below values in birds maintained throughout in SD. Fife Fancy thus does not seem to develop absolute but only relative refractoriness. The relatively high singing activity expressed by SD‐photosensitive males does not seem to depend on high testosterone (T) concentrations. Singing did not correlate with plasma testosterone (T). Treatment with ATD + Flutamide only marginally decreased song rate and did not affect song quality nor song control nuclei volume. These birds are either supersensitive to low T levels or their reproductive physiology is activated by other mechanisms. Neurogenesis is increased by T and by LD but the function of new neurons incorporated in HVC is poorly understood. We developed a procedure based on X‐ray focal irradiation to deplete neural progenitors adjacent to HVC and study the functional consequences. The decrease in neurogenesis increased the variability of T‐induced songs in females and decreased their bandwidth. Neurogenesis in HVC thus plays a role in song production and X‐ray focal irradiation represents an excellent tool to analyze adult neurogenesis. [ABSTRACT FROM AUTHOR]

Links between the regulation of growth and energy balance are clear; to fuel growth, there must be consumption of energy. Therefore, it is perhaps intuitive that interactions between the hypothalamic – pituitary – growth hormone axis (growth axis) and pathways that drive metabolic processes exist. Overproduction of growth hormone has been associated with diabetes and metabolic disease for decades and the opposing effects of growth hormone and insulin have been studied since early experiments almost a century ago. The relationship between neuroendocrine axes can be complex and the growth axis is no exception, interacting with energy balance in several organ systems, both in the periphery and centrally in hypothalamic nuclei. Much is known about peripheral interactions between growth axis hormones and processes such as glucose homeostasis and adipogenesis. More is still being learned about the molecular actions of growth axis hormones in adipose and other metabolically active tissues, and recent findings are discussed in this perspective. However, less is known about interactions with central energy balance pathways in the hypothalamus. This perspective aims to summarise what is known about these interactions, taking lessons from human studies and animal genetic and seasonal models, and discusses what this may mean in an evolving landscape of personalised medicine. [ABSTRACT FROM AUTHOR]

Across taxa, the seasonal transition between non‐breeding and breeding states is controlled by localised thyroid hormone signalling in the deep brain via reciprocal switching of deiodinase enzyme expression from type 3 (DIO3) to type 2 (DIO2). This reciprocal switch is considered to be mediated by increasing thyroid‐stimulating hormone β (TSHβ) release from the pars tuberalis, which occurs in response to a change in photoperiod. Although well characterised in a handful of model organisms in controlled laboratory settings, this pathway remains largely unexplored in free‐living animals under natural environmental conditions. In this comparative gene expression study, we investigated hypothalamic thyroid hormone signalling in two seasonally breeding subspecies of white‐crowned sparrow (Zonotrichia leucophrys), across the entirety of their annual cycles. The migratory Gambel's (Z. l. gambelii) and resident Nuttall's (Z. l. nuttalii) subspecies differ with respect to timing of reproduction, as well as life history stage and migratory strategies. Although DIO3 mRNA expression was elevated and DIO2 mRNA expression was reduced in the wintering period in both subspecies, DIO2 peaked in both subspecies prior to the onset of reproduction. However, there was differential timing between subspecies in peak DIO2 expression. Intriguingly, seasonal modulation of TSHβ mRNA was only observed in migrants, where expression was elevated at the start of breeding, consistent with observations from other highly photoperiodic species. There was no correlation between TSHβ, DIO2 and gonadotropin‐releasing hormone‐I mRNA or reproductive metrics in residents. Based on these observed differences, we discuss potential implications for our understanding of how changes in medial basal hypothalamic gene expression mediates initiation of seasonal reproduction. [ABSTRACT FROM AUTHOR]

Gerald Anthony Lincoln died after a short illness on 15 July 2020 at the age of 75 years. Gerald was Emeritus Professor of Biological Timing at Edinburgh University and a Fellow of the Royal Society of Edinburgh. He was an outstanding scientist and naturalist who was a seminal figure in developing our understanding of the neuroendocrine mechanisms underlying seasonal rhythmicity. This review considers his life and some of his major scientific contributions to our understanding of seasonality, photoperiodism and circannual rhythmicity. It is based on a presentation at the online 2nd annual seasonality symposium (2 October 2020) that was supported financially by the Journal of Neuroendocrinology. [ABSTRACT FROM AUTHOR]

Part of the life cycle of several fish species includes important salinity changes, as is the case for the sea bass (Dicentrarchus labrax) or the Atlantic salmon (Salmo salar). Salmo salar juveniles migrate downstream from their spawning sites to reach seawater, where they grow and become sexually mature. The process of preparation enabling juveniles to migrate downstream and physiologically adapt to seawater is called smoltification. Daily and seasonal variations of photoperiod and temperature play a role in defining the timing of smoltification, which may take weeks to months, depending on the river length and latitude. Smoltification is characterised by a series of biochemical, physiological and behavioural changes within the neuroendocrine axis. This review discusses the current knowledge and gaps related to the neuroendocrine mechanisms that mediate the effects of light and temperature on smoltification. Studies performed in S. salar and other salmonids, as well as in other species undergoing important salinity changes, are reviewed, and a particular emphasis is given to the pineal hormone melatonin and its possible role in osmoregulation. The daily and annual variations of plasma melatonin levels reflect corresponding changes in external photoperiod and temperature, which suggests that the hormonal time‐keeper melatonin might contribute to controlling smoltification. Here, we review studies on (i) the impact of pinealectomy and/or melatonin administration on smoltification; (ii) melatonin interactions with hormones involved in osmoregulation (e.g., prolactin, growth hormone and cortisol); (iii) the presence of melatonin receptors in tissues involved in osmoregulation; and (iv) the impacts of salinity changes on melatonin receptors and circulating melatonin levels. Altogether, these studies show evidence indicating that melatonin interacts with the neuroendocrine pathways controlling smoltification, although more information is needed to clearly decipher its mechanisms of action. [ABSTRACT FROM AUTHOR]

Seasonal neuroendocrine cycles that govern annual changes in reproductive activity, energy metabolism and hair growth are almost ubiquitous in mammals that have evolved at temperate and polar latitudes. Changes in nocturnal melatonin secretion regulating gene expression in the pars tuberalis (PT) of the pituitary stalk are a critical common feature in seasonal mammals. The PT sends signal(s) to the pars distalis of the pituitary to regulate prolactin secretion and thus the annual moult cycle. The PT also signals in a retrograde manner via thyroid‐stimulating hormone to tanycytes, which line the ventral wall of the third ventricle in the hypothalamus. Tanycytes show seasonal plasticity in gene expression and play a pivotal role in regulating local thyroid hormone (TH) availability. Within the mediobasal hypothalamus, the cellular and molecular targets of TH remain elusive. However, two populations of hypothalamic neurones, which produce the RF‐amide neuropeptides kisspeptin and RFRP3 (RF‐amide related peptide 3), are plausible relays between TH and the gonadotrophin‐releasing hormone‐pituitary‐gonadal axis. By contrast, the ways by which TH also impinges on hypothalamic systems regulating energy intake and expenditure remain unknown. Here, we review the neuroendocrine underpinnings of seasonality and identify several areas that warrant further research. [ABSTRACT FROM AUTHOR]

Many animals synchronise their reproductive activity with the seasons to optimise the survival of their offspring. This synchronisation involves switching on and off their gonadotrophic axis. Ever since their discovery as key regulators of gonadotrophin-releasing hormone (GnRH) neurones, the hypothalamic RF-amide peptides kisspeptin and RFamide-related peptide (RFRP) have been a major focus of research on the seasonal regulation of the gonadotrophic axis. In the present study, we investigated the regulation of both neuropeptides in the Djungarian hamster, a major animal model for the study of seasonal reproduction. During the long-day breeding period, kisspeptin neurones in the anteroventral periventricular area are solely controlled by a positive sex steroid feedback and, in the arcuate nucleus, they are subject to a very strong negative sex steroid feedback associated with a minor photoperiodic effect. During short-day sexual quiescence, the disappearance of this hormonal feedback leads to high levels of kisspeptin in arcuate neurones. Notably, chronic central administration of kisspeptin is able to over-ride the photoperiodic inhibition of the gonadotrophic axis and reactivate the reproductive function. Therefore, our data suggest that kisspeptin secretion by arcuate neurones during sexual quiescence is inhibited by mechanisms upstream of kisspeptin neurones. RFRP expression is solely controlled by photoperiod, being strongly reduced in short days independently of the sex steroid feedback. Thus, kisspeptin and RFRP display contrasting patterns of expression and regulation. Upstream mechanisms controlling these neurones should be the focus of further studies on the roles of these RFamide neuropeptides in the seasonal control of reproduction. [ABSTRACT FROM AUTHOR]

Neuroendocrine structures integrate a vast range of external cues and internal signals that, in turn, result in adaptive physiological responses. Emerging data indicate that light, social cues, stress and energy balance stimulate relatively short-and long-term genomic modifications in discrete neuroendocrine structures, which are mediated by epigenetic mechanisms. Moreover, environmentally-induced fluctuations in the synthesis of local hypothalamic and circulating hormones provide an internal signal that contributes to the extensive neuroendocrine genomic plasticity. This review examines the impact of environmental stimuli and endogenous hormonal signals on the regulation of epigenetic enzymes in key neuroendocrine structures. The data discussed are predominantly derived from studies in the neuroendocrine control of seasonal reproduction and the impact of social stress in rodent models. The perspective presented considers the role of oestrogen and glucocorticoids as the primary catalysts for inducing epigenetic modifications (eg, DNA methylation) in specific neuroendocrine structures. Oestrogen and glucocorticoid actions suggest: (i) a preferential action for specific epigenetic enzymes and (ii) nucleus-and cell-specific modifications. Untangling the complex web of hormonal regulation of methylation and acetylation will enhance our understanding of short-and long-term changes in epigenetic enzymes that generate adaptive and pathological neuroendocrine responses. [ABSTRACT FROM AUTHOR]

The present study investigated seasonal alterations in the daily rhythms of hypothalamic expression of genes involved in the photoperiodic regulation of annual cycles in birds. We measured the 4-hourly mRNA expression of genes involved in the photoperiodic transduction (OPN5, EYA3, CGA, TSHβ, DIO2, DIO3) and neurosteroid-dependent processes (AR, CYP19, ERα, ERβ) in the hypothalamus of migratory blackheaded buntings photoinduced with photosensitive, photostimulated (early and late stimulated) and photorefractory seasonal states. There were significant differences in daily mRNA profiles between the photoperiodic states. Particularly, increased CGA, TSHβ and DIO2 and decreased DIO3 mRNA levels in the early photostimulated state, compared to the photosensitive state, suggest that thyroid hormones have a role in photostimulation in buntings. Similar differences in the expression of genes coding for the aromatase enzyme (CYP19) and receptors for oestrogen (ERα, ERβ) (but not androgen; AR) indicate that there is seasonal alteration in the neuro-oestrogen-mediated functions. Furthermore, peak expression times of CGA, TSHβ and DIO2 genes at hours 14-15 of the day in the early stimulated state indicated molecular regulation of the daily rhythm of photoinducibility in buntings. Most significantly, however, we found an attenuated daily rhythm in thyroid hormone modulatory genes and a switch of peak expression time from day to night in CYP19 mRNA rhythm in the subsequent late photostimulated state, although testicular maturation still persisted. These alterations in daily rhythms may have signalled the initiation of processes underlying other seasonal phenologies in parallel with the gonadal response, such as a manifestation of the night-time flight in buntings. These results show alterations in daily rhythms underlying the transcriptional regulation of the photoperiod-induced seasonal states in migratory blackheaded buntings. [ABSTRACT FROM AUTHOR]

Wnt signalling and its downstream effectors are well known for their roles in embryogenesis and tumourigenesis, including the regulation of cell proliferation, survival and differentiation. In the nervous system, Wnt signalling has been described mainly during embryonic development, although accumulating evidence suggests that it also plays a major role in adult brain morphogenesis and function. Studies have predominantly concentrated on memory formation in the hippocampus, although recent data indicate that Wnt signalling is also critical for neuroendocrine control of the developed hypothalamus, a brain centre that is key in energy balance regulation and whose dysfunction is implicated in metabolic disorders such as type 2 diabetes and obesity. Based on scattered findings that report the presence of Wnt molecules in the tanycytes and ependymal cells lining the third ventricle and arcuate nucleus neurones of the hypothalamus, their potential importance in key regions of food intake and body weight regulation has been investigated in recent studies. The present review brings together current knowledge on Wnt signalling in the hypothalamus of adult animals and discusses the evidence suggesting a key role for members of the Wnt signalling family in glucose and energy balance regulation in the hypothalamus in diet-induced and genetically obese (leptin deficient) mice. Aspects of Wnt signalling in seasonal (photoperiod sensitive) rodents are also highlighted, given the recent evidence indicating that the Wnt pathway in the hypothalamus is not only regulated by diet and leptin, but also by photoperiod in seasonal animals, which is connected to natural adaptive changes in food intake and body weight. Thus, Wnt signalling appears to be critical as a modulator for normal functioning of the physiological state in the healthy adult brain, and is also crucial for normal glucose and energy homeostasis where its dysregulation can lead to a range of metabolic disorders. [ABSTRACT FROM AUTHOR]

Seasonal or photoperiodically sensitive animals respond to altered day length with changes in physiology (growth, food intake and reproductive status) and behaviour to adapt to predictable yearly changes in the climate. Typically, different species of hamsters, voles and sheep are the most studied animal models of photoperiodism. Although laboratory rats are generally considered nonphotoperiodic, one rat strain, the inbred Fischer 344 ( F344) rat, has been shown to be sensitive to the length of daylight exposure by changing its physiological phenotype and reproductive status according to the season. The present study aimed to better understand the nature of the photoperiodic response in the F344 rat. We examined the effects of five different photoperiods on the physiological and neuroendocrine responses. Young male F344 rats were held under light schedules ranging from 8 h of light/day to 16 h of light/day, and then body weight, including fat and lean mass, food intake, testes weights and hypothalamic gene expression were compared. We found that rats held under photoperiods of ≥ 12 h of light/day showed increased growth and food intake relative to rats held under photoperiods of ≤ 10 h of light/day. Magnetic resonance imaging analysis confirmed that these changes were mainly the result of a change in lean body mass. The same pattern was evident for reproductive status, with higher paired testes weight in photoperiods of ≥ 12 h of light/day. Accompanying the changes in physiological status were major changes in hypothalamic thyroid hormone ( Dio2 and Dio3), retinoic acid ( Crabp1 and Stra6) and Wnt/β-Catenin signalling genes ( sFrp2 and Mfrp). Our data demonstrate that a photoperiod schedule of 12 h of light/day is interpreted as a stimulatory photoperiod by the neuroendocrine system of young male F344 rats. [ABSTRACT FROM AUTHOR]

In seasonal animals, photoperiod exerts profound effects on physiology, such as growth, energy balance and reproduction, via changes in the neuroendocrine axes. A key element of the photoperiodic response is the thyroid hormone level in the hypothalamus, which is controlled via retrograde transport of thyroid-stimulating hormone (TSH) from the pars tuberalis of the pituitary. TSH regulates type II deiodinase (Dio2) expression, which transforms inactive thyroid hormone to its active form, via TSH receptors expressed in the ependymal cells of the hypothalamus. In the present study, we hypothesised that a second peptide hormone, neuromedin U (NMU), may play a role in the photoperiodic response alongside TSH because the gene for NMU is also expressed in a strongly photoperiod-dependent manner in the pars tuberalis and its receptor NMU2 is expressed in the ependymal layer of the third ventricle in photoperiod-sensitive F344 rats. Consistent with other studies conducted in nonseasonal mammals, we found that acute i.c.v. injections of NMU into the hypothalamus negatively regulated food intake and body weight and increased core body temperature in F344 rats. At the same time, NMU increased Dio2 mRNA expression in the ependymal region of the hypothalamus similar to the effects of TSH. These data suggest that NMU may affect acute and photoperiodically controlled energy balance through distinct pathways. We also showed that TSH inhibits the expression of type III deiodinase (Dio3) in F344 rats, a response not mimicked by NMU. Furthermore, NMU also increased the expression of genes from the Wnt/β-catenin pathway within the ependymal layer of the third ventricle. This effect was not influenced by TSH. These data indicate that, although NMU acts with some similarities to TSH, it also has completely distinct signalling functions that do not overlap. In summary, the present study of NMU signalling reveals the potential for a new player in the control of seasonal biology. [ABSTRACT FROM AUTHOR]

In mammals, the medio-basal hypothalamus (MBH) integrates photoperiodic and food-related cues to ensure timely phasing of physiological functions, including seasonal reproduction. The current human epidemics of obesity and associated reproductive disorders exemplifies the tight link between metabolism and reproduction. Yet, how food-related cues impact breeding at the level of the MBH remains unclear. In this respect, the sheep, which is a large diurnal mammal with a marked dual photoperiodic/metabolic control of seasonal breeding, is a relevant model. Here, we present a large-scale study in ewes (n = 120), which investigated the impact of food restriction (FRes) on the MBH transcriptome using unbiased RNAseq, followed by RT-qPCR. Few genes (~100) were impacted by FRes and the transcriptional impact was very modest (<2-fold increase or < 50% decrease for most genes). As anticipated, FRes increased expression of Npy/AgRP/LepR and decreased expression of Pomc/Cartpt, while Kiss1 expression was not impacted. Of particular interest, Eya3, Nmu and Dio2, genes involved in photoperiodic decoding within the MBH, were also affected by FRes. Finally, we also identified a handful of genes not known to be regulated by food-related cues (e.g., RNase6, HspA6, Arrdc2). In conclusion, our transcriptomics study provides insights into the impact of metabolism on the MBH in sheep, which may be relevant to human, and identifies possible molecular links between metabolism and (seasonal) reproduction., (© 2022 British Society for Neuroendocrinology.)

The production of bioactive peptides from biologically inactive precursors involves extensive post-translational processing, including enzymatic cleavage by proteolytic peptidases. Endoproteolytic prohormone-convertases initially cleave the precursors of many neuropeptides at specific amino acid sequences to generate intermediates with basic amino acid extensions on their C-termini. Subsequently, the related exopeptidases, carboxypeptidases D and E ( CPD and CPE), are responsible for removing these amino acids before the peptides achieve biological activity. We investigated the effect of photoperiod on the processing of the neuropeptide precursor pro-opiomelanocortin ( POMC) and its derived neuropeptides, α- melanocyte-stimulating hormone ( MSH) and β -endorphin ( END), within the hypothalamus of the seasonal Siberian hamster ( Phodopus sungorus). We thus compared hypothalamic distribution of CPD, CPE, α- MSH and β- END using immunohistochemistry and measured the enzyme activity of CPE and concentrations of C-terminally cleaved α - MSH in short-day ( SD; 8 : 16 h light/dark) and long-day ( LD; 16 : 8 h light/dark) acclimatised hamsters. Increased immunoreactivity (-IR) of CPE, as well as higher CPE activity, was observed in SD. This increase was accompanied by more β- END-IR cells and substantially higher levels of C- terminally cleaved α- MSH, as determined by radioimmunoassay. Our results suggest that exoproteolytic cleavage of POMC-derived neuropeptides is tightly regulated by photoperiod in the Siberian hamster. Higher levels of biological active α- MSH- and β- END in SD are consistent with the hypothesis that post-translational processing is a key event in the regulation of seasonal energy balance. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the actions of fibroblast growth factor 21 ( FGF21) on energy balance in a natural model of relative fatness, the Siberian hamster. Hamsters were studied under long days ( LD) to promote weight gain, or short days to induce weight loss, and treated with rh FGF21 (3 mg/kg/day) via s.c. minipumps for 14 days. On days 7-9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made. FGF21 caused substantial (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD. Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found in SD. Body weight loss in LD was associated with a reduction in food intake (P < 0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected. These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype. The observed differences in FGF21 sensitivity may relate to day length-induced changes in adipose tissue mass. [ABSTRACT FROM AUTHOR]

Links between the regulation of growth and energy balance are clear; to fuel growth, there must be consumption of energy. Therefore, it is perhaps intuitive that interactions between the hypothalamic - pituitary - growth hormone axis (growth axis) and pathways that drive metabolic processes exist. Overproduction of growth hormone has been associated with diabetes and metabolic disease for decades and the opposing effects of growth hormone and insulin have been studied since early experiments almost a century ago. The relationship between neuroendocrine axes can be complex and the growth axis is no exception, interacting with energy balance in several organ systems, both in the periphery and centrally in hypothalamic nuclei. Much is known about peripheral interactions between growth axis hormones and processes such as glucose homeostasis and adipogenesis. More is still being learned about the molecular actions of growth axis hormones in adipose and other metabolically active tissues, and recent findings are discussed in this perspective. However, less is known about interactions with central energy balance pathways in the hypothalamus. This perspective aims to summarise what is known about these interactions, taking lessons from human studies and animal genetic and seasonal models, and discusses what this may mean in an evolving landscape of personalised medicine., (© 2022 The Author. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

To maximise reproductive success, organisms restrict breeding to optimal times of the day or year, when internal physiology and external environmental conditions are suitable for the survival of both parent and offspring. To appropriately coordinate reproductive activity, internal and external standing is communicated to the hypothalamic-pituitary-gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. The cumulative balance of these mediators ultimately drives the pattern of gonadotrophin-releasing hormone secretion, a neurohormone that stimulates pituitary gonadotrophin secretion. Until 2000, a complementary inhibitor of pituitary gonadotrophin secretion had not been identified. At this time, a novel, avian hypothalamic peptide capable of inhibiting gonadotrophin secretion in cultured quail pituitary cells was uncovered and named gonadotrophin-inhibitory hormone (GnIH). Subsequently, the presence and functional role for the mammalian orthologue of GnIH, RFamide-related peptide, (RFRP-3), was examined, confirming a conserved role for this peptide across several rodent species. To date, a similar distribution and functional role for RFRP-3 have been observed across all mammals investigated, including humans. This overview summarises the role that RFRP-3 plays in mammals and considers the implications and opportunities for further study with respect to reproductive physiology and the neural control of sexual behaviour and motivation. [ABSTRACT FROM AUTHOR]

The differential effect of long (LD; 16 : 8 h light/dark), short (SD; 10 : 14 h light/dark) and natural day length (NDL; 12 : 12 h light/dark) during the reproductively inactive (RIP) and active (RAP) phases was assessed in relation to immunity and reproductive function of a tropical rodent Funambulus pennanti. They presented high immunity and low testicular activity during RIP and an opposite during RAP. SD increased spleen and thymus weight, leukocyte and lymphocyte counts, cell mediated immunity [i.e. blastogenic response in terms of percentage stimulation ratio of splenocytes and thymocytes (when challenged with concanavalin A)] and delayed type hypersensitivity to oxazolone. SD during RIP increased the above mentioned parameters and reduced testes weight compared to NDL groups. During RAP, LD reduced all the immunological parameters when compared with NDL and SD experiencing groups of RIP and RAP phases. The LD group reduced the immunological parameters compared to RAP, suggesting that LD had always an inhibitory effect on immune status being independent of reproductive phases. The intensity of the stimulatory effects of SD and inhibitory effects of LD during both reproductive phases was significantly different. We exposed another set of squirrels to the above photoperiodic schedule for prolonged period (30 weeks) during RAP. A clear testicular refractoriness followed by immunorefractoriness was observed in the group experiencing SD and LD for 30 weeks. The photorefractoriness presented by the testes was inversely related to the immunorefractoriness. The peripheral melatonin level of those squirrels reflected the photoperiodic signal perceived by squirrels for immunomodulation and gonadal function, suggesting that immune system and gonadal function might have coevolved. [ABSTRACT FROM AUTHOR]

For many temperate-zone avian species, termination of breeding occurs when individuals no longer respond to previously stimulatory day lengths, a condition called photorefractoriness. Long day lengths induce significantly greater expression of c-fos and fos-related antigens (FRAs) in the tuberal hypothalamus of the photosensitive hen than that of the photorefractory hen. The tuber is also a site of photoinducible glial expression of type 2 iodothyronine deiodinase (Dio2), which converts thyroxine into its active form, triiodothyronine (T3). T3 induces withdrawal of glial processes from gonadotrophin-releasing hormone (GnRH) I nerve terminals, which is believed to permit the efficient release of GnRH I into the associated portal vasculature. Using a riboprobe, we tested whether long days induce Dio2 mRNA expression in the turkey tuber and, if so, whether this expression is reduced in photorefractory hens. Long days significantly induced rostral and caudal tuberal hypothalamic Dio2 expression in photosensitive hens. Photorefractory hens had reduced expression of Dio2 with most subjects expressing no detectable mRNA in the rostral tuber and variably attenuated amounts throughout the medial and caudal tuber. We also performed double-label immunohistochemistry to identify co-localisation between FRAs and glial fibrillary acidic protein, a glial marker. FRAs were present in the nuclei of a few astrocytes in the median eminence and infundibular nucleus of the tuber. The temporal and spatial coincidence between FRA and Dio2 expression, their mutual association with glia, and the attenuation of their response during photorefractoriness suggests that the two events are linked and that photorefractoriness involves a reduced capacity for photo-inducible gene expression within glia of the tuberal hypothalamus. [ABSTRACT FROM AUTHOR]

Photoperiodic responses enable animals to adapt their physiology to predictable patterns of seasonal environmental change. In mammals, this depends on pineal melatonin secretion and effects in the hypothalamus, but the cellular and molecular substrates of its action are poorly understood. The recent identification of a mammalian orthologue of the avian gonadotrophin-inhibitory hormone gene has led to interest in its possible involvement in seasonal breeding. In long-day breeding Syrian hamsters, hypothalamic RFamide-related peptide (RFRP) expression is increased by exposure to long photoperiod. Because, opposite to hamsters, sheep are short-day breeders, we predicted that a conserved role in mammalian reproductive activation would decrease RFRP expression in sheep under a long photoperiod. We cloned the ovine RFRP cDNA and examined its expression pattern in Soay sheep acclimated to a 16 : 8 h or 8 : 16 h light /dark cycle (LP and SP, respectively). RFRP was expressed widely in the sheep hypothalamus and increased modestly overall with exposure to LP. Interestingly, RFRP expression in the ependymal cells surrounding the base of the third ventricle was highly photoperiodic, with levels being undetectable in animals held on SP but consistently high under LP. These data are inconsistent with a conserved reproductive role for RFRP across mammals. Additionally, we cloned the ovine homologue of the cognate RFRP receptor, rfr-2 (NPFF1) and found localised expression in the suprachiasmatic nuclei and in the pars tuberalis. Taken together, these data strengthen the emerging view that interplay between ependymal cells and the pars tuberalis might be important for the seasonal timing system. [ABSTRACT FROM AUTHOR]

Seasonal rhythms of body weight, reflecting altered food intake, energy storage and expenditure, are a common feature of mammals inhabiting temperate and arctic latitudes. They have evolved so that predictable annual changes in the external environment can be anticipated and animals can adjust their physiology and behaviour in preparation for the changing demands of the seasons. These long-term changes in energy balance are not simply effected by the brain centres and peptidergic pathways known to underlie short-term homeostatic regulation. Screens of altered gene expression in Siberian hamsters comparing the anabolic summer state in long photoperiods and the catabolic ‘winter’ state in short photoperiods have identified differential gene expression in the hypothalamus. The majority of gene expression changes are confined to two restricted areas: the dorsomedial posterior arcuate nucleus, and the ventral ependymal layer of the third ventricle. Functions encoded by these ‘seasonal’ genes include thyroid hormone metabolism, retinoic acid and histaminergic signalling, and VGF and secretogranin production. The changes in thyroid hormone availability that are brought about by differential activity of deiodinase enzymes are of particular importance because experimental manipulation of central thyroid levels can prevent seasonal cyclicity. Given the importance of thyroid hormone in the initial development of the brain, we hypothesise that thyroid hormone-dependent plasticity of hypothalamic connections and neurogenesis underlie seasonal cycles of food intake and body weight. [ABSTRACT FROM AUTHOR]

The present study tested the hypothesis that seasonal intervals of exposure to modest changes in photoperiod, typical of those experienced by humans living in temperate latitudes (10–14 h light/day), engage changes in emotional behaviour of Wistar rats, a commonly-used animal model for investigations of affective physiology. Short day lengths (≤ 12 h light/day) induced behavioural despair in a forced-swim test, exploratory anxiety in an open field arena, and anhedonia in a two-bottle sucrose preference task, relative to longer day lengths. Plasma adrenocorticotrophic hormone was lower in short-day relative to long-day rats, but testosterone and corticosterone concentrations were comparable across treatments. In common with animals that engage reproductive responses to day length, reproductively nonresponsive mammals such as Wistar rats exhibit changes in affective state following small changes in day length. Wistar rats may provide an animal model for the study of seasonal mood regulation because the neuroendocrine, depressive, anxious and anhedonic responses of Wistar rats to short days bear similarities to those observed in some human populations. Standard laboratory husbandry practices (exposure to a 12 : 12 h light/dark cycle) may inadvertently deliver a chronic background depressive and anxiogenic stimulus. [ABSTRACT FROM AUTHOR]

The pars tuberalis (PT) of the adenohypophysis expresses a high density of melatonin receptors and is thought to be a crucial relay for the actions of melatonin on seasonal rhythmicity of prolactin secretion by the pars distalis (PD). In common with the suprachiasmatic nucleus of the hypothalamus and most other peripheral tissues, the PT rhythmically expresses a range of ‘clock genes’. Interestingly, this expression is highly dependent upon melatonin/photoperiod, with several aspects unique to the PT. These observations led to the establishment of a conceptual framework for the encoding of seasonal timing in this tissue. This review summarises current knowledge of the morphological, functional and molecular aspects of the PT and considers its role in seasonal timing. The strengths and weaknesses of current hypotheses that link melatonin action in the PT to its seasonal effect on lactotrophs of the PD are discussed and alternative working hypotheses are suggested. [ABSTRACT FROM AUTHOR]

Day length (photoperiod) is a powerful synchroniser of seasonal changes in the reproductive neuroendocrine activity in temperate-zone birds. When exposed to light during the photoinducible phase, reproductive neuroendocrine responses occur. However, the neuroendocrine systems involved in avian reproduction are poorly understood. We investigated the effect of light exposure at different circadian times upon the hypothalamus and components of the circadian system, using c-fos mRNA expression, measured by in situ hybridisation, as an indicator of light-induced neuronal activity. Levels of c-fos mRNA in these areas were compared after turkey hens (on a daily 6-h light period) had been exposed to a 30-min period of light occurring at 8, 14, or 20 h after the onset of first light of the day (subjective dawn). Non-photostimulated control birds were harvested at the same times. In birds, photostimulated within the photoinducibile phase (14 h), in contrast to before or after, c-fos mRNA was significantly increased in the nucleus commissurae pallii (nCPa), nucleus premamillaris (PMM), eminentia mediana (ME), and organum vasculosum lamina terminalis (OVLT). Photostimulation increased c-fos mRNA expression in the pineal gland, nucleus suprachiasmaticus, pars visualis (vSCN) and nucleus inferioris hypothalami compared to that of their corresponding nonphotostimulated controls. However, the magnitudes of the responses in these areas were similar irrespective of where in the dark period the pulses occurred. No c-fos mRNA was induced in the nucleus infundibulari, in response to the 30-min light period at any of the circadian times tested. The lack of c-fos up-regulation in the pineal gland and vSCN following photostimulation during the photoinducible phase lends credence to the hypothesis that these areas are not involved in the photic initiation of avian reproduction. On the other hand, c-fos mRNA increases in the nCPa, ME, and OVLT support other studies showing that these areas are involved in the onset of reproductive behaviour initiated by long day lengths. The present study provides novel data showing that the PMM in the caudal hypothalamus is involved in the neuronally mediated, light-induced initiation of reproductive activity in the turkey hen. [ABSTRACT FROM AUTHOR]

Our previous studies using turkey hens have demonstrated that c-fos mRNA (a marker of neuronal activation) is expressed in gonadotrophin-releasing hormone-I (GnRH-I), vasoactive intestinal peptide (VIP) and dopamine (DA) neurones following electrical stimulation in the preoptic area. DA has been shown to have both stimulatory and inhibitory effects on the GnRH-I/luteinising hormone (LH), follicle-stimulating hormone (FSH) and VIP/prolactin (PRL) systems. To identify the DA neurones that mediate the stimulatory influences of photoperiod on the reproductive system, we examined c-fos mRNA induction in DA, GnRH-I, and VIP neurones in the turkey hypothalamus using a dark-interruption experimental design. A 30-min light period was provided to short day (6L : 18D) photosensitive turkeys at times when birds were responsive to light (14 h after first light) and at times when birds were unresponsive to light (8 h and 20 h after first light). The only area where DA neurones were activated when the birds were provided with light was in the nucleus premammillaris (PMM). The number of activated DA neurones was significantly greater when light was provided at 14 h (during the photoinducible phase) than at 8 h or 20 h. At 14 h, there was also an increase in the number of GnRH-I neurones activated in the area of the nucleus commissura pallii (nCPa), as well as an up-regulation of GnRH-I mRNA expression. No expression of c-fos mRNA was observed in VIP neurones in the nucleus infundibularis or up-regulation of VIP mRNA expression in any of the experimental light treatments. These results are the first evidence to demonstrate a relationship between the dopaminergic system in the PMM and the GnRH-I system in the nCPa during the photoinduction of avian reproductive activity. [ABSTRACT FROM AUTHOR]

Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5–50 mg/kg body weight; i.p.) and central (0.5 µg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function. [ABSTRACT FROM AUTHOR]

We have previously shown that cold-acclimated (8 °C) male field voles ( Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity. [ABSTRACT FROM AUTHOR]

Siberian hamsters exhibit several seasonal rhythms in physiology and behaviour, including reproduction, energy balance, body mass, and pelage colouration. Unambiguous long- and short day lengths stimulate and inhibit reproduction, respectively. Whether gonadal growth or regression occurs in an intermediate day length (e.g. 14 h L : 10 h D; 14L), depends on whether the antecedent day lengths were shorter (10L) or longer (16L). Variations in day length are encoded by the duration of nocturnal pineal melatonin secretion, which is decoded at several neural melatonin target tissues to control testicular structure and function. We assessed participation of three such structures in the acquisition and retrieval of day length information. Elimination of melatonin signalling to the nucleus reuniens (NRe), but not to the suprachiasmatic nucleus (SCN) or paraventricular thalamus (PVt), interfered with the acquisition of a long day reproductive response, whereas the obscuring of melatonin signals to the SCN and the NRe, but not to the PVt, interfered with the photoperiod history response. The SCN and NRe contribute in different ways to the melatonin-based system that mediates seasonal rhythms in male reproduction. [ABSTRACT FROM AUTHOR]

A remarkable feature of the seasonal adaptation displayed by the Siberian hamster ( Phodopus sungorus) is the ability to decrease food intake and body weight (by up to 40%) in response to shortening photoperiod. The regulating neuroendocrine systems involved in this adaptation and their neuroanatomical and molecular bases are poorly understood. We investigated the effect of photoperiod on the expression of prohormone convertases 1 (PC1/3) and 2 (PC2) and the endoproteolytic processing of the neuropeptide precursor pro-opiomelanocortin (POMC) within key energy balance regulating centres of the hypothalamus. We compared mRNA levels and protein distribution of PC1/3, PC2, POMC, adrenocorticotrophic hormone (ACTH), α-melanocyte-stimulating hormone (MSH), β-endorphin and orexin-A in selected hypothalamic areas of long day (LD, 16 : 8 h light : dark), short day (SD, 8 : 16 h light : dark) and natural-day (ND, photoperiod depending on time of the year) acclimated Siberian hamsters. The gene expression of PC2 was significantly higher within the arcuate nucleus (ARC, P < 0.01) in SD and in ND (versus LD), and is reflected in the day length profile between October and April in the latter. PC1/3 gene expression in the ARC and lateral hypothalamus was higher in ND but not in SD compared to the respective LD controls. The immunoreactivity of PC1/3 cleaved neuropeptide ACTH in the ARC and PC1/3-colocalised orexin-A in the latyeral hypothalamus were not affected by photoperiod changes. However, increased levels of PC2 mRNA and protein were associated with higher abundance of the mature neuropeptides α-MSH and β-endorphin (P < 0.01) in SD. This study provides a possible explanation for previous paradoxical findings showing lower food intake in SD associated with decreased POMC mRNA levels. Our results suggest that a major part of neuroendocrine body weight control in seasonal adaptation may be effected by post-translational processing mediated by the prohormone convertases PC1/3 and PC2, in addition to regulation of gene expression of neuropeptide precursors. [ABSTRACT FROM AUTHOR]

Siberian hamsters ( Phodopus sungorus) undergo reproductive involution following exposure to short winter day lengths. Following approximately 20 weeks of exposure to short day (SD) lengths, hamsters become refractory to the inhibitory effects of SD, and reproductive competence is restored in anticipation of spring. The extent to which changes in gonadal steroid-dependent and -independent regulation of gonadotrophin secretion participate in this vernal reactivation of the gonads is not known. This experiment tested whether tonic and gonadotrophin-releasing hormone (GnRH)-stimulated regulation of lutenising hormone (LH) secretion differs between photoresponsive and photorefractory Siberian hamsters. Male hamsters born into long day (LD) lengths were castrated or subjected to a sham-castration surgery at 17 days of age, implanted s.c. with blank or testosterone-filled capsules, and housed in LD or SD thereafter. Baseline LH and LH responses to GnRH (200 ng/kg, s.c) were measured at 14 (photoresponsive) and 40 (photorefractory) weeks of age. Despite lower circulating testosterone concentrations in gonadally regressed SD hamsters on week 14, tonic LH concentrations were comparable among all groups of gonad-intact hamsters on weeks 14 and 40; however, week 14 SD hamsters exhibited significantly higher GnRH-stimulated LH responses. Tonic LH concentrations were indistinguishable among all groups of castrated hamsters bearing empty implants on week 14, but prolonged exposure to LD led to a decrease in resting LH, whereas prolonged exposure to SD resulted in an increase in LH. In castrated hamsters bearing testosterone implants, baseline LH concentrations were comparable in all groups, but GnRH treatment resulted in significantly higher LH concentrations in photorefractory (week 40, SD) hamsters relative to all other groups. The data suggest that the development of photorefractoriness in Siberian hamsters is characterised by enhanced gonadal hormone-independent stimulation of LH secretion, and diminished sensitivity to inhibitory negative-feedback effects of testosterone on LH secretion. Decreases in responsiveness of gonadotrophin secretion to gonadal hormone negative feedback may contribute to the process of photorefractoriness and assist in maintaining the growth of reproductive organs during the process of gonadal recrudescence. [ABSTRACT FROM AUTHOR]

The Siberian hamster, Phodopus sungorus, exhibits a remarkable cycle of body weight, reproduction and leptin sensitivity in response to a seasonal change in photoperiod. In the present study, we investigated the hypothesis that the suppressor of cytokine signalling 3 (SOCS3) plays a critical role in the regulation of the seasonal body weight cycle. We analysed arcuate nucleus SOCS3 gene expression in short day length (SD; 8 : 16 h light/dark) acclimated Siberian hamsters that were transferred back to long day length (LD; 16 : 8 h light/dark) and in hamsters that spontaneously became photorefractory to SD induced by prolonged exposure. SD acclimated hamsters that were transferred back to LD for 1, 2, 3, 4 or 6 weeks, increased arcuate nucleus SOCS3 gene expression to the LD level within 2 weeks, and maintained this higher level thereafter. The early increase of SOCS3 gene expression preceded the LD-induced rise in body weight by approximately 3 weeks. Hamsters kept in SD for an extended period (25 weeks), began to become refractory to SD and to increase body weight. By this time, there was no difference in level of SOCS3 gene expression between LD and SD photoperiods, although body weight was still suppressed in SD hamsters. Finally, we addressed whether SOCS3 gene expression is related to SD-induced gonadal regression or to body weight decrease by comparing Siberian hamsters with Syrian hamsters. The latter exhibited substantial SD-induced gonadal regression but only limited seasonal changes in body weight. Acclimation to either LD or SD for 14 weeks had no effect on SOCS3 gene expression. This implies that arcuate nucleus SOCS3 gene expression is unlikely to be related to seasonal cycles in reproductive activity. Taken together, the findings further strengthen our hypothesis that SOCS3 may be one molecular trigger of seasonal cycles in body weight. [ABSTRACT FROM AUTHOR]

Many nontropical animals display physiological and behavioural changes in response to seasonal environmental cues including photoperiod (day length). Male Siberian hamsters (Phodopus sungorus) housed in short photoperiod undergo testicular regression accompanied by reduced circulating testosterone and decreased reproductive behaviour. By contrast to the majority of small mammals studied, aggressive behaviour is elevated in short-day Siberian hamsters when blood testosterone concentrations are not detectable. Because gonadal steroid hormones influence neuronal nitric oxide synthase (nNOS), and this enzyme has been implicated in aggressive behaviour, we hypothesized that nNOS expression would be decreased in short-day male Siberian hamsters and negatively correlated with the display of territorial aggression. Adult male Siberian hamsters were individually housed in either long (LD 16 : 8 h) or short (LD 8 : 16 h) photoperiods for 10 weeks. Hamsters were assigned to one of two categories by assessing testicular volume and plasma testosterone values: (i) photoperiodic responsive (i.e. regressed testes and low testosterone concentrations) or (ii) photoperiodic nonresponsive (i.e. testes size and circulating testosterone concentrations equivalent to hamsters maintained in long days). At week 10, aggression was assessed using a resident–intruder test. Latency to initial attack, frequency of attacks and duration of total attacks were recorded during a 10-min aggression trial. Brains were collected immediately after behavioural testing and stained for nNOS expression using immunohistochemistry. All short day-housed hamsters were significantly more aggressive than long-day animals, regardless of gonadal size or testosterone concentrations. Short-day animals, both reproductively responsive and nonresponsive morphs, also had significantly less nNOS-immunoreactive cells in the anterior and basolateral amygdaloid areas and paraventricular nuclei compared to long-day hamsters. Together, these results suggest that seasonal aggression in male Siberian hamsters is regulated by photoperiod, through mechanisms that are likely independent from gonadal steroid hormones. [ABSTRACT FROM AUTHOR]

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHSR). However, the functional interaction of ligand and receptor is not very well understood. We demonstrate that GHSR mRNA is up-regulated after food deprivation (48 h) in the hypothalamic arcuate nucleus and ventromedial nucleus of the seasonal Siberian hamster,Phodopus sungorus. This increase is accompanied by a two-fold elevation of circulating ghrelin concentration. Chronic changes in feeding state imposed by food restriction over a period of 12 weeks during long day-length induced increased GHSR gene expression, whereas food restriction for 6 weeks had no effect.Phodopus sungorusreveals remarkable seasonal changes in body weight, fat mass and circulating leptin levels. Ghrelin is generally regarded as having opposing effects on appetite and body weight with respect to those exhibited by leptin. However, our study revealed that seasonal adaptations were not accompanied by changes in either GHSR gene expression or circulating ghrelin concentration. Therefore, we suggest that ghrelin only plays a minor role in modulating long-term seasonal body weight cycles. Our findings imply that ghrelin predominantly acts as a short-term regulator of feeding. [ABSTRACT FROM AUTHOR]

Abstract In the Siberian hamster, Phodopus sungorus , short-day photoperiods induce the winter phenotype, which in males includes a decrease in the production of androgens and changes in physiology to inhibit reproduction. Motoneurones of the spinal nucleus of the bulbocavernosus (SNB) and their target muscles, the bulbocavernosus and the levator ani, a neuromuscular system involved in male copulation, also display seasonal plasticity in P. sungorus . It is not known whether the plasticity seen in the SNB system of gonadally intact hamsters is due to the effects of photoperiod per se , or to the photoperiod-induced changes in androgen production. To answer this question, we castrated adult male hamsters from long days and then implanted them with capsules containing either testosterone or blanks. Half of the hamsters from each hormone condition were moved into short photoperiod (8 : 16 h light/dark cycle) while the rest were maintained under long-day conditions (15 : 9 h light/dark cycle). After 15 weeks, many measures of the SNB system, such as somata size and weight of target muscles, responded only to androgen, not to photoperiod. However, there were effects of photoperiod on the neuromuscular junctions (NMJs) that were independent of androgen status. For example, the number of synaptic zones per NMJ and the area of the NMJs were significantly increased by short days and/or testosterone treatment. The two factors exerted an additive, rather than an interactive, effect on these measures. Another striated muscle, the extensor digitorum longus, which is present in both sexes and plays no specialized role in reproduction, displayed neither an effect of androgen nor of photoperiod on fibre size or NMJ structure. These results suggest that, in addition to androgenic effects on SNB plasticity, there is also an androgen-independent effect of photoperiod on the SNB neuromuscular system. [ABSTRACT FROM AUTHOR]

Abstract The role of noradrenaline (NA) and dopamine (DA) in the hypothalamic control of prolactin (PRL) secretion was investigated in hypothalamic intact (control) and hypothalamo-pituitary disconnected (HPD) Soay rams. The animals were exposed to alternating 16-weekly periods of short (8 L : 16D) and long days (16 L : 8D) to induce marked cyclical changes in PRL secretion in both groups (as demonstrated previously). Selective NA and DA receptor antagonists (dose: 1.2 µmol/kg) were administered under short days (low endogenous PRL secretion), and agonists (dose: 0.0012–0.12 µmol/kg) were administered under long days (high endogenous PRL secretion). The acute changes in blood PRL concentrations were measured over 4 h as the index of responsiveness. Under short days, treatment with WB4101 (α-1 adenoceptor antagonist), and rauwolscine (α-2 antagonist), consistently increased PRL secretion in control, but not in HPD rams. The treatments produced similar acute, drug-specific behavioural effects in both groups. Propranolol (β antagonist) had no effect on PRL secretion, while sulpiride (DA D-2 antagonist) induced a marked increase in blood PRL concentrations in control rams (> 4 h), and a transient effect in HPD rams (15 min). Under long days, when endogenous PRL secretion was increased, phenylephrine (α-1 agonist) produced no effects, while bromocriptine (DA D-2 agonist) robustly decreased PRL concentrations in both control and HPD rams, even at the lowest treatment dose. Overall, the positive responses to the antagonists in the control rams, support the view that DA (acting via D-2 receptors), and to a lesser extent NA (acting via α-1/α-2 receptors), negatively regulate PRL secretion. In contrast, the lack of responses to the antagonists in the HPD rams, support the view that neither DA, nor NA, mediate the photoperiodic control of PRL secretion. [ABSTRACT FROM AUTHOR]

AbstractSyrian hamsters exhibit a marked seasonal variation in prolactin secretion. The aim of this study was to analyse the nature of the photoperiodic regulation of prolactin gene expression, and to define the role of melatonin and the pars tuberalis of the anterior pituitary in this process. Pituitary prolactin gene expression, restricted to the pars distalis, was increased in hamsters maintained in long daylengths (16 h : 8 h, light : dark) compared to hamsters exposed to short daylengths (8 h : 16 h, light : dark) for 8–12 weeks. Analysis of single cells by in situ hybridization showed that photoperiod had no effect on the percentage of pars distalis cells expressing prolactin mRNA, but shifted the frequency distribution of prolactin mRNA expression per cell, such that in long photoperiods a greater proportion of cells were recruited to a higher expressing population. In vitro coculture of hamster pars tuberalis fragments increased prolactin promoter-driven luciferase activity in stably transfected GH3 cells in a dose- and duration-dependent manner. Conditioned medium from hamster and ovine pars tuberalis also activated the prolactin promoter. Furthermore, basal and forskolin-stimulated conditioned medium from hamster pars tuberalis increased prolactin mRNA expression in primary cultures of pars distalis cells. Melatonin attenuated the activity of pars tuberalis-conditioned medium but had no direct effect on either prolactin mRNA expression or secretion in pars distalis cell cultures. Finally, pars tuberalis fragments from long photoperiod hamsters stimulated prolactin gene promoter activity to a greater extent than those from short photoperiod hamsters. In conclusion, this study provides the first evidence in a seasonal mammal that the synthesis of prolactin depends on photoperiodic modulation of a pars tuberalis-derived factor. Our data support further the hypothesis that seasonal modulation of prolactin gene expression depends upon a melatonin-dependent paracrine action of the pars tuberalis on pars distalis lactotrophic cells. [ABSTRACT FROM AUTHOR]

Abstract Sheep experience well-documented seasonal changes in reproductive activity and voluntary food intake (VFI). Within the hypothalamus, neurones that express neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) have been implicated in the regulation of reproduction and appetite. In this study, we aimed to determine the extent to which the expression of these two neuronal systems is linked to the seasonal reproductive cycle and/or the seasonal appetite cycle. VFI in our sheep reaches a nadir in August with no difference occurring between December and February. We examined the brains of ovariectomized (OVX) female sheep (n = 5–7) that were killed during the breeding season (February) or during the early or late nonbreeding season (August and December, respectively). The brains of these animals were perfused with paraformaldehyde and processed for in situ hybridization histochemistry, using ribonucleotide probes labelled with 35S. The number of NPY and POMC cells and the number of silver grains per cell were counted using an image analysis system. For NPY, the number of cells counted in the arcuate nucleus/median eminence region and the number of silver grains per cell was significantly lower in animals killed during August than in animals killed in February or December. The number of grains per cell over NPY cells was also significantly lower in animals killed during August. For POMC, the number of cells was lower in February than in August and December. Similarly, the number of grains per cell for POMC were lower in February than in August and December. VFI was significantly lower in animals during August than at other times of the year. We conclude that in OVX ewes: (i) NPY gene expression is lower at the time of the year when VFI is reduced and (ii) POMC gene expression is greater at the time of the nonbreeding season than during the breeding season. Because these results were obtained in OVX animals, the changes appear to be independent of alterations in the secretion and/or action of ovarian steroids. Thus, the activity of NPY neurones appears to relate to changes in appetite whereas changes in POMC expression may be relevant to the seasonal breeding cycle. [ABSTRACT FROM AUTHOR]

Durational melatonin signals, cued by the photoperiod and generated by the pineal gland, are processed in the brain to induce seasonally appropriate physiological and behavioural adaptations. The melatonin receptor subtype MEL1a (also known as mt1) appears to regulate seasonal responses. Single label in situ hybridization for MEL1a receptor mRNA revealed labelled cells in several brain regions of Siberian hamsters, including the suprachiasmatic nucleus, the paraventricular nucleus of the thalamus, and the reuniens nucleus of the thalamus. To characterize suprachiasmatic nucleus cells containing MEL1a receptor mRNA, we used 35S-labelled cRNA probes for MEL1a receptor mRNA in combination with digoxigenin-labelled cRNA probes for vasopressin, somatostatin, or orphan retinoid Z receptor β (RZRβ; a putative nuclear melatonin receptor). Cells in the suprachiasmatic nucleus that contained MEL1a receptor mRNA also contained mRNAs for vasopressin and RZRβ, but not for somatostatin. These data suggest that suprachiasmatic nucleus vasopressin cells may respond to melatonin signals, raising the possibility that suprachiasmatic nucleus vasopressin output mediates some of the effects of melatonin on seasonal or circadian responses. [ABSTRACT FROM AUTHOR]

The endocrine function of the pars tuberalis of the pituitary gland has been an enigma for many years. Recent work suggests that one of its primary functions in seasonal mammals is to mediate photoperiodically regulated changes in prolactin secretion via an unidentified factor called tuberalin. [ABSTRACT FROM AUTHOR]

Synchronization of mammalian breeding activity to the annual change of photoperiod and environmental conditions is of the utmost importance for individual survival and species perpetuation. Subsequent to the early 1960s, when the central role of melatonin in this adaptive process was demonstrated, our comprehension of the mechanisms through which light regulates gonadal activity has increased considerably. The current model for the photoperiodic neuroendocrine system points to pivotal roles for the melatonin-sensitive pars tuberalis (PT) and its seasonally-regulated production of thyroid-stimulating hormone (TSH), as well as for TSH-sensitive hypothalamic tanycytes, radial glia-like cells located in the basal part of the third ventricle. Tanycytes respond to TSH through increased expression of thyroid hormone (TH) deiodinase 2 (Dio2), which leads to heightened production of intrahypothalamic triiodothyronine (T3) during longer days of spring and summer. There is strong evidence that this local, long-day driven, increase in T3 links melatonin input at the PT to gonadotropin-releasing hormone (GnRH) output, to align breeding with the seasons. The mechanism(s) through which T3 impinges upon GnRH remain(s) unclear. However, two distinct neuronal populations of the medio-basal hypothalamus, which express the (Arg)(Phe)-amide peptides kisspeptin and RFamide-related peptide-3, appear to be well-positioned to relay this seasonal T3 message towards GnRH neurons. Here, we summarize our current understanding of the cellular, molecular and neuroendocrine players, which keep track of photoperiod and ultimately govern GnRH output and seasonal breeding., (© 2022 British Society for Neuroendocrinology.)

Vasopressin (VP) is an important hormone produced in the supraoptic (SON) and paraventricular nucleus (PVN) with antidiuretic and vasoconstrictor functions in the periphery. As one of the first discovered peptide hormones, VP was also shown to act as a neurotransmitter, where VP is produced and released under the influence of various stimuli. VP is one of the core signals via which the biological clock, the suprachiasmatic nucleus (SCN), imposes its rhythm on its target structures and its production and release is influenced by the rhythm of clock genes and the light/dark cycle. This is contrasted with VP production and release from the bed nucleus of the stria terminalis and the medial amygdala, which is influenced by gonadal hormones, as well as with VP originating from the PVN and SON, which is released in the neural lobe and central targets. The release of VP from the SCN signals the near arrival of the resting phase in rodents and prepares their physiology accordingly by down-modulating corticosterone secretion, the reproductive cycle and locomotor activity. All these circadian variables are regulated within very narrow boundaries at a specific time of the day, where day-to-day variation is less than 5% at any particular hour. However, the circadian peak values can be at least ten times higher than the circadian trough values, indicating the need for an elaborate feedback system to inform the SCN and other participating nuclei about the actual levels reached during the circadian cycle. In short, the interplay between SCN circadian output and peripheral feedback to the SCN is essential for the adequate organisation of all circadian rhythms in physiology and behaviour., (© 2021 British Society for Neuroendocrinology.)

Aggression is a complex social behaviour that allows individuals to compete for access to limited resources (eg, mates, food and territories). Excessive or inappropriate aggression, however, has become problematic in modern societies, and current treatments are largely ineffective. Although previous work in mammals suggests that aggressive behaviour varies seasonally, seasonality is largely overlooked when developing clinical treatments for inappropriate aggression. Here, we investigated how the hormone melatonin regulates seasonal changes in neurosteroid levels and aggressive behaviour in Siberian hamsters, a rodent model of seasonal aggression. Specifically, we housed males in long-day (LD) or short-day (SD) photoperiods, administered timed s.c. melatonin injections (which mimic a SD-like signal) or control injections, and measured aggression using a resident-intruder paradigm after 9 weeks of treatment. Moreover, we quantified five steroid hormones in circulation and in brain regions associated with aggressive behaviour (lateral septum, anterior hypothalamus, medial amygdala and periaqueductal gray) using liquid chromatography-tandem mass spectrometry. SD hamsters and LD hamsters administered timed melatonin injections (LD-M) displayed increased aggression and exhibited region-specific decreases in neural dehydroepiandrosterone, testosterone and oestradiol, but showed no changes in progesterone or cortisol. Male hamsters also showed distinct associations between neurosteroids and aggressive behaviour, in which neural progesterone and dehydroepiandrosterone were positively correlated with aggression in all treatment groups, whereas neural testosterone, oestradiol and cortisol were negatively correlated with aggression only in LD-M and SD hamsters. Collectively, these results provide insight into a novel neuroendocrine mechanism of mammalian aggression, in which melatonin reduces neurosteroid levels and elevates aggressive behaviour., (© 2021 British Society for Neuroendocrinology.)