Influence Of Melatonin Research Articles

Melatonin signaling in T cells: Functions and applications.

Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T-cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T-cell biology and the beneficial effects of melatonin in T-cell response-based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. Meanwhile, melatonin is highly effective in modulating T-cell activation and differentiation, especially for Th17 and Treg cells, and also memory T cells. Mechanistically, the influence of melatonin in T-cell biology is associated with membrane and nuclear receptors as well as receptor-independent pathways, for example, via calcineurin. Several cell signaling pathways, including ERK1/2-C/EBPα, are involved in the regulatory roles of melatonin in T-cell biology. Through modulation in T-cell responses, melatonin exerts beneficial effects in various inflammatory diseases, such as type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. These findings highlight the importance of melatonin signaling in T-cell fate determination, and T cell-based immune pathologies.

Obesity: The role of desynchronosis and genetic factors in mechanisms of its development

The article highlights the role of desynchronosis and certain genetic factors in the development of obesity. Some pathogenetic links of obesity and the influence of melatonin on them are analyzed.Desynchronosis is one of the causes of obesity as a result of dysregulatory changes in the chronoperiodic system – between suprachiasmatic nuclei of the hypothalamus and secretory activity of the pineal gland.In obesity there are some changes in circadian patterns of important physiological parameters. These include acrophases of blood pressure; rhythm of hormone secretion, including insulin; electrolytes; sleep-wake cycle displaced for a period of a day, which is a deviation from the normal course. Phase discrepancies of established circadian oscillations of physiological processes arise. Preconditions of fat metabolism imbalance, particularly visfatin, apelin and vaspin – components of atherosclerotic lesions, gradually emerge.There is abundant evidence for close relationships between metabolism and circadian mechanisms. It is proved, that there is a strong direct impact of endogenous circadian rhythms on the metabolic pathways that do not depend on food intake or sleep. A potential low molecular weight of biomarkers of human circadian phases has been identified. A number of key metabolic enzymes in tissues such as the liver, adipose tissue or the pancreas are chronodependent. Desynchronosis phenomena caused by genetic or environmental factors can lead to serious metabolic disorders, including obesity, insulin resistance and metabolic syndrome.Genesis of pineal removal-induced insulin resistance and reduced glucose tolerance in cells is related to the consequences of melatonin absence, which leads to abnormalities in insulin signaling pathways and reduced GLUT4 gene expression and protein content.Insulin-sensitive tissues (white and brown adipose tissue, skeletal and heart muscles) after pineal removal are characterized by a significant reduction of GLUT4 mRNA and the content of microsomal and membrane proteins, which are compensated during treatment by melatonin. Functional synergy exists between melatonin and insulin. Melatonin is able through the membrane receptors MT1 to cause rapid tyrosine phosphorylation, activate tyrosine kinase of beta subunits of insulin receptors and mobilize several intracellular stages of insulin-signaling pathway transduction.Thus, the protective effect of melatonin in cases of disturbance to the carbohydrate metabolism is manifested in the formation of circadian periodicity by modulating the expression of time genes.

The influence and role of melatonin on in vitro oocyte maturation and embryonic development in pig and cattle

The influence and role of melatonin on in vitro oocyte maturation and embryonic development in pig and cattle

The role of melatonin in pathogenesis of cardiovascular diseases

The results presented, of laboratory and clinical studies of melatonine role in pathogenesis of cardiovascular diseases as arterial hypertension, coronary pathology. The influence of melatonin on atherogenesis is described, its impact on platelet aggregation. Increase of melatonin production in cardiovascular patients is probably the result of compensatory mechanisms activation at the stage of functional disorders with further exhaustion of compensatory mechanisms towards somatic disease development. As the severity of cardiovascular pathology increases, general production of melatonin declines, as well as its rhythmic of production turns disordered.

Influences of exogenous melatonin on the oocyte growth and oxidative status of ovary during different reproductive phases of an annual cycle in carp Catla catla

The present study aimed to evaluate antioxidant role of melatonin in determining seasonality of ovarian growth in adult carp Catla catla. Accordingly, an identical regimen of exogenous melatonin administration (100 μg/100 g body weight per day for 15 days) was followed during the preparatory, prespawning, and spawning phases of an annual reproductive cycle. The study did not include postspawning phase, when the ovaries were completely regressed and devoid of any healthy growing follicles. The ovarian response was evaluated by determining relative number of developing oocytes as well as measuring the levels of melatonin, oxidative stress (using malondialdehyde [MDA] as the marker), both enzymatic (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], and glutathione S-transferase [GST]) and nonenzymatic (reduced glutathione [GSH]) antioxidants in the ovarian homogenates. Due to melatonin treatment, oocyte growth was accelerated in the preparatory phase but retarded in the prespawning and spawning phases of annual cycle. Conversely, melatonin administration in each reproductive phase led to a significant reduction of MDA and elevations of SOD, CAT, GPx, GST, GSH, as well as melatonin levels in the ovary. As a result, melatonin titers in the ovary always reported a negative correlation with MDA and a positive correlation with SOD, CAT, GST, GPx, as well as GSH levels. However, melatonin content of ovary and the values of gonosomatic index in melatonin-treated carp displayed a positive correlation in the preparatory phase and a negative correlation in the remaining parts of reproductive cycle. Thus, it seems likely that melatonin by acting as an antioxidant reduces intraovarian oxidative stress throughout the seasons of follicular growth, whereas exogenous melatonin administration exerts progonadal influences during the preparatory phase, but antigonadal effects during the prespawning and spawning phases of reproductive cycle.

Morphological and functional changes in kidneys caused by propranolol: effects of melatonin.

Background. Beta-blockers, including propranolol, are widely used in clinical practice as effective heart medicines. By the spectrum of action, some of them are selectively blocking beta-blockers, which are located in the heart muscle, and called cardioselective (nebivolol, metoprolol, atenolol). Others (propranolol, oksyprenolol, pindolol), simultaneously affect β1- and β2-adrenergic receptors, referred to as non-selective. Objective. The aim of our study was to examine the value of blockade of beta-adrenergic receptors in the regulation of chronorhythms of excretory and ion-regulative renal functions. Determine the possible role of exogenous melatonin in mechanisms of correction of circadian renal function disorders and morphologic abnormalities of kidneys. M ethods. Experiments conducted on 35 male rats. One group of rats was daily administered by intragastric propranolol at a dose of 2,5 mg/kg body weight at 19.00 for 7 days. Another group of rats received intraperitoneal exogenous melatonin (Sigma, USA) (0,5 mg/kg body weight) at standard daylight against previous administration of propranolol. Results . Our studies showed that exogenous melatonin is able to influence the basic parameters of renal function caused by propranolol. Obviously, these effects are realized by stimulating specific melatonin receptors located on the basolateral membrane of the initial divisions of proximal tubules, and to a lesser extent – in the glomeruli. Thus, administration of melatonin on the background of propranolol action increases the urine output, increases the speed of ultrafiltration in glomeruli at 42 %, reduces the effects of azotemia, increases the excretion of sodium, increases proximal and distal transport of this cation. Conclusion . The influence of melatonin in condition of propranolol action was characterized by pleiotropic effect.

Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway

Exogenous administration of melatonin has been demonstrated to down-regulate inflammatory responses and attenuate organ damage in various models. However, the salutary effect of melatonin against secondary intra-abdominal hypertension (IAH) remains unclear. This study sought to test the influence of melatonin on secondary IAH in a pathophysiological rat model and the underlying mechanisms involved. Before resuscitation, male rats underwent a combination of induced portal hypertension, applying an abdominal restraint device, and hemorrhaging to mean arterial pressure (MAP) of 40mmHg for 2h. After blood reinfusion, the rats were treated with lactated Ringer solution (LR) (30mL/h), melatonin (50mg/kg) +LR, and SB-203580 (10μmol/kg)+LR. LR was continuously infused for 6h. MAP, the inferior vena cava pressure and urine output were monitored. Histopathological examination, immunofluorescence of tight junction proteins, and transmission electron microscopy were administered. Intestinal permeability, myeloperoxidase activity, malondialdehyde, glutathione peroxidase, and levels of TNF-a, IL-2, and IL-6, were assessed. The expression of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, translocation of nuclear factor kappa B subunit, signal transducers and activators of transcription and tight junction proteins were detected by Western blot. We found that melatonin inhibited the inflammatory responses, decreased expression of p38 MAPK, attenuated intestinal injury, and prevented secondary IAH. Moreover, administration of SB203580 abolished the increase in p38 MAPK and also attenuated intestinal injury. These data indicate that melatonin exerts a protective effect in intestine in secondary IAH primarily by attenuating the inflammatory responses which are in part attributable to p38 MAPK inhibition.

Exogenous Melatonin Improves Antioxidant Defense in Cucumber Seeds (Cucumis sativus L.) Germinated under Chilling Stress.

The relationship between exogenous melatonin applied into cucumber seeds during osmopriming and modifications of their antioxidant defense was studied. Accumulation of hydrogen peroxide, antioxidant enzyme activities and glutathione pool were investigated in embryonic axes isolated from the control, osmoprimed, and osmoprimed with melatonin seeds. Germinating cucumber seeds are very sensitive to chilling. Temperature 10°C causes oxidative stress in young seedlings. Seed pre-treatment with melatonin seemed to limit H2O2 accumulation during germination under optimal condition as well as during chilling stress and recovery period. Melatonin affected superoxide dismutase (SOD) activity and its isoforms during stress and recovery period but did not influence CAT and POX activities. Thus it is possible that in cucumber this indoleamine could act mostly as a direct H2O2 scavenger, but superoxide anion combat via SOD stimulation. The GSH/GSSG ratio is considered as an indirect determinant of oxidative stress. When the cells are exposed to oxidative stress GSSG is accumulated and the ratio of GSH to GSSG decreases. In our research pre-sowing melatonin application into the cucumber seeds caused high beneficial value of GSH/GSSG ratio that could be helpful for stress countering. Glutathione reductase (GSSG-R) activity in the axes isolated from these seeds was two fold higher than in those isolated from the control and from the osmoprimed without melatonin ones. Additional isoforms of GSSG-R in melatonin treated seeds were also observed. It explains high and effective GSH pool restoration in the seeds pre-treated with melatonin. We confirmed that melatonin could protect cucumber seeds and young seedlings against oxidative stress directly and indirectly detoxifying ROS, thereby plants grown better even in harmful environmental conditions. This work is the first that investigated on plant in vivo model and documented melatonin influence on redox state during seed germination. This way we try to fill lack of information about melatonin-regulated pathways involved in antioxidant strategy of plant defense.

Natural melatonin fluctuation and its minimally invasive simulation in the zebra finch.

Melatonin is a key hormone in the regulation of circadian rhythms of vertebrates, including songbirds. Understanding diurnal melatonin fluctuations and being able to reverse or simulate natural melatonin levels are critical to investigating the influence of melatonin on various behaviors such as singing in birds. Here we give a detailed overview of natural fluctuations in plasma melatonin concentration throughout the night in the zebra finch. As shown in previous studies, we confirm that “lights off” initiates melatonin production at night in a natural situation. Notably, we find that melatonin levels return to daytime levels as early as two hours prior to the end of the dark-phase in some individuals and 30 min before “lights on” in all animals, suggesting that the presence of light in the morning is not essential for cessation of melatonin production in zebra finches. Thus, the duration of melatonin production seems not to be specified by the length of night and might therefore be less likely to directly couple circadian and annual rhythms. Additionally, we show that natural melatonin levels can be successfully simulated through a combination of light-treatment (daytime levels during subjective night) and the application of melatonin containing skin-cream (nighttime levels during subjective day). Moreover, natural levels and their fluctuation in the transition from day to night can be imitated, enabling the decoupling of the effects of melatonin, for example on neuronal activity, from sleep and circadian rhythmicity. Taken together, our high-resolution profile of natural melatonin levels and manipulation techniques open up new possibilities to answer various melatonin related questions in songbirds.

Influence of melatonin on IL-1Ra gene and IL-1 expression in rats with liver ischemia reperfusion injury.

The aim of the present study was to explore the influence of melatonin (MT) on rats with liver ischemia reperfusion injury (IRI) and its mechanism. A total of 66 male Sprague-Dawley rats were randomly divided into 3 groups: i) Normal control group, ii) ischemia reperfusion group (IR group) and iii) melatonin treatment group (MT group). Rats in the MT group were administered an intraperitoneal injection of MT (10 mg/kg, 1 ml) at 70 and 35 min before ischemia, early reperfusion, and 1 and 2 h after reperfusion, respectively. Blood was removed at the normal time-point (prior to any processes), 35 min before ischemia, 2, 4, 8 and 24 h after reperfusion. Subsequently the rats were sacrificed. The pathological changes of liver tissues, interleukin-1 receptor antagonist (IL-1Ra) gene and IL-1 expression levels were detected. There were no evident differences between the immediate reperfusion and 2 h IR group and MT group. The liver structure injury of the 4, 8 and 24 h MT groups were improved to various differences compared to the corresponding IR group; liver IL-1β of the MT group at 35 min after ischemia, and 2, 4, 8 and 24 h after reperfusion was evidently lower than that of the IR group (P<0.05); IL-1Ra mRNA expression in the 2 h MT group was higher compared to the 2 h IR group by 4.85-fold; and IL-1Ra mRNA expression in the 4 h MT group was higher compared to the 4 h IR group by 9.34-fold. Differences between two groups at other time-points were <2-fold. In conclusion, MT can upregulate IL-1Ra gene expression by reducing generation of IL-1 thus reducing IRI.

The influence of melatonin and dexamethasone instillations on the clinical course of uveitis and the biochemical processes in the aqueous humour of the anterior chamber of the eye (an experimental study)

Introduction. The problem of the treatment of uveitis has the important socio-medical implications bearing in mind the high prevalence of this pathological condition frequently affecting the subjects of the employable age. Uveitis is characterized by the enhanced production of free radicals in the eye tissues and marked activation of oxidative reactions that gradually aggravate the pronounced changes in the immune system that, in their turn, promote the development of oxidative stress. Aim. This study was designed to evaluate and compare the influence of melatonin and dexamethasone or their combination on the clinical symptoms and local metabolic processes in the aqueous humour of the anterior chamber of the rabbit eyes. Materials and methods. The present study was based on the rabbit model of immunogenic anterior uveitis developed by the subcutaneous injections of the normal equine serum followed by its intravitreal administration. We investigated the influence of instillations of a 0.1% melatonin solution and a 0.4% dexamethasone solution or their combinations on the clinical course of uveitis and the biochemical processes in the aqueous humour of the anterior chamber of the eye including the anti-oxidative activity, total protein and alpha-2 macroglobulin contents as well as the leukocyte count. Results. It was shown that instillation of melatonin either alone or in a combination with the dexamethasone solution reduced the severity of the inflammatory processes associated with uveitis. Melatonin, similar to dexamethasone, decreased palpebral oedema and iridial swelling. The two medication instilled successively produced a synergic effect on palpebral oedema, conjunctival hyperemia, corneal and iridial oedema. A significant decrease of protein and alpha-2 macroglobulin levels in comparison with the same values in the aqueous humour of the anterior chamber of the eye of the untreated animals was documented within 8 days after the induction of experimental uveitis. The similar effects of dexamethasone was even more pronounced. At the same time, the instillation of melatonin more significantly than that of dexamethasone reduced the number of leukocytes in the aqueous humour of the anterior chamber. It is worthwhile to note that instillations of melatonin, unlike those of dexamethasone, caused a significant increase in the anti-oxidative activity in the aqueous humour of the anterior chamber. Discussion. The instillations of melatonin make it possible to reduce the intensity of the inflammatory processes associated with experimental uveitis, enhance the anti-oxidative potential in the eye tissues, and decrease the permeability of the blood-ocular barrier. Conclusion. It is concluded that the introduction of melatonin instillations in the combined treatment of uveitis may improve the effectiveness of therapy of this condition.

The influence of melatonin on the parameters of cerebral hemodynamics in patients with hypertensive disease

The authors discuss the results of application of melatonin in patients with hypertensive disease. Treatment with melatonin facilitated normalization of arterial pressure and cerebral hemodynamics at night time.

Melatonin increased maize (Zea mays L.) seedling drought tolerance by alleviating drought-induced photosynthetic inhibition and oxidative damage

The effect of melatonin application on enhancing plant stress tolerance is already known, but the specifics of its performance and its underlying mechanism are still poorly understood. The influences of foliar-sprayed melatonin (100 μmol/L) on maize (Zea mays L.) seedlings growth during drought stress were investigated in this study. The growth of seedlings was not affected by melatonin application under normal conditions. After 8 days of drought stress, growth was significantly inhibited, but this inhibition was alleviated by foliar-spraying with melatonin. After rehydration, melatonin-treated plants recovered more quickly than untreated plants. Further investigation showed that, under drought condition, melatonin-treated plants showed higher photosynthetic rates, stomatal conductances and transpiration rates than those untreated plants. Compared with untreated plants, the melatonin-treated plants exhibited low osmotic potential under drought stress, which contributed to the maintenance of high turgor potential and relative water content. Drought stress induced the accumulation of hydrogen peroxide and malondialdehyde, but the accumulation was decreased by melatonin application. Also, both enzymatic and nonenzymatic antioxidant activity were enhanced by melatonin application under drought stress. These results imply that the effects of melatonin on enhancing drought tolerance can be ascribed to the alleviation of drought-induced photosynthetic inhibition, improvement in plant water status, and mitigation of drought-induced oxidative damage. The results suggest that melatonin could be considered as a potential plant growth regulator for the improvement of crop drought tolerance in crop production.

The role of melatonin in pathogenesis of cardiovascular diseases

The results presented, of laboratory and clinical studies of melatonine role in pathogenesis of cardiovascular diseases as arterial hypertension, coronary pathology. The influence of melatonin on atherogenesis is described, its impact on platelet aggregation. Increase of melatonin production in cardiovascular patients is probably the result of compensatory mechanisms activation at the stage of functional disorders with further exhaustion of compensatory mechanisms towards somatic disease development. As the severity of cardiovascular pathology increases, general production of melatonin declines, as well as its rhythmic of production turns disordered.

Melatonin influence on circadian rhythms

Melatonin influence on circadian rhythms

The Influence of Melatonin on Immune System and Cancer

C l i n M e d International Library Citation: Vinther AG, Claesson MH (2015) The Influence of Melatonin on Immune System and Cancer. Int J Cancer Clin Res 2:024 Received: May 20, 2015: Accepted: September 17, 2015: Published: September 19, 2015 Copyright: © 2015 Vinther AG. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Vinther and Claesson. Int J Cancer Clin Res 2015, 2:3

Melatonin attenuates (-)-epigallocatehin-3-gallate-triggered hepatotoxicity without compromising its downregulation of hepatic gluconeogenic and lipogenic genes in mice.

(-)-Epigallocatehin-3-gallate (EGCG), a major constituent of green tea, can ameliorate metabolic syndrome at least in part through reducing gluconeogenesis and lipogenesis. Green tea extracts, of which EGCG is a key constituent, have been used for weight loss in humans. A potential adverse effect of high-dose EGCG or green tea extracts is hepatotoxicity. Melatonin, an endogenous antioxidant with a high safety profile, is effective in preventing various types of tissue damage. The current study investigated the influence of melatonin on EGCG-triggered hepatotoxicity and EGCG-downregulated hepatic genes responsible for gluconeogenesis and lipogenesis in mice. We found that (i) melatonin extended survival time of mice intoxicated with lethal doses of EGCG; (ii) melatonin ameliorated acute liver damage and associated hepatic Nrf2 suppression caused by a nonlethal toxic dose of EGCG; (iii) melatonin reduced subacute liver injury and hepatic Nrf2 activation caused by lower toxic doses of EGCG; and (iv) melatonin did not compromise the action of pharmacological doses of EGCG in downregulating a battery of hepatic genes responsible for gluconeogenesis and lipogenesis, including G6Pc, PEPCK, FOXO1α, SCD1, Fasn, leptin, ACCα, ACCβ, GAPT, and Srebp-1. Taken together, these results suggest that the combination of EGCG and melatonin is an effective approach for preventing potential adverse effects of EGCG as a dietary supplement for metabolic syndrome alleviation and body weight reduction.

Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats.

Neurogenic pulmonary edema (NPE) is a serious non-neurological complication that can occur after a subarachnoid hemorrhage (SAH) and is associated with decreased survival and a poor neurological outcome. Melatonin is a strong antioxidant that has beneficial effects against SAH in rats, including reduced mortality and reduced neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model, however, have not been clearly identified. This study was undertaken to determine the influence of melatonin on SAH-induced NPE and the potential mechanism of these effects using the filament perforation model of SAH in male Sprague Dawley rats. Either melatonin (150 mg/kg) or a vehicle was given via an intraperitoneal injection 2 hr after an SAH induction. Lung samples were extracted 24 hr after SAH. The results show that the melatonin treatment attenuated SAH-induced NPE by preventing alveolar-capillary barrier dysfunctions via inhibiting the disruption of tight junction proteins (ZO-1 and occludin). Moreover, the treatment downregulated the levels of mature interleukin (IL) -1β, myeloperoxidase (MPO), and matrix metallopeptidase (MMP) 9 expression/activation, which were increased in the lung; also, melatonin treatment improved neurological deficits. Furthermore, the melatonin treatment markedly reduced caspase-3 activity and the number of TUNEL-positive cells in the lung. Taken together, these findings show that administration of melatonin attenuates NPE by preventing alveolar-capillary barrier dysfunctions via repressing the inflammatory response and by anti-apoptosis effects after SAH.

Endocrinology of osmoregulation and thermoregulation of Australian desert tetrapods: A historical perspective

Many Australian tetrapods inhabit desert environments characterised by low productivity, unpredictable rainfall, high temperatures and high incident solar radiation. Maintaining a homeostatic milieu intérieur by osmoregulation and thermoregulation are two physiological challenges faced by tetrapods in deserts, and the endocrine system plays an important role in regulating these processes. There is a considerable body of work examining the osmoregulatory role of antidiuretic hormones for Australian amphibians, reptiles and mammals, with particular contributions concerning their role and function for wild, free-living animals in arid environments. The osmoregulatory role of the natriuretic peptide system has received some attention, while the role of adrenal corticosteroids has been more thoroughly investigated for reptiles and marsupials. The endocrinology of thermoregulation has not received similar attention. Reptiles are best-studied, with research examining the influence of arginine vasotocin and melatonin on body temperature, the role of prostaglandins in heart rate hysteresis and the effect of melanocyte-stimulating hormone on skin reflectivity. Australian mammals have been under-utilised in studies examining the regulation, development and evolution of endothermy, and there is little information concerning the endocrinology of thermoregulation for desert species. There is a paucity of data concerning the endocrinology of osmoregulation and thermoregulation for Australian desert birds. Studies of Australian desert fauna have made substantial contributions to endocrinology, but there is considerable scope for further research. A co-ordinated approach to examine arid-habitat adaptations of the endocrine system in an environmental and evolutionary context would be of particular value.

The Effects of Melatonin on Brain Arginine Vasotocin: Relationship with Sex and Seasonal Differences in Melatonin Receptor Type 1 in Green Treefrogs (Hyla cinerea).

The neuroendocrine mechanisms by which animals synchronise their physiological state with environmental cues are vital to timing life-history events appropriately. One important endocrine transducer of environmental cues in vertebrates is the pineal hormone melatonin, the secretion of which is directly sensitive to photoperiod and temperature. Melatonin modulates arginine vasotocin (AVT)-immunoreactive (-IR) cell number in the brain of green treefrogs (Hyla cinerea) during the summer breeding season, and this modulation is sexually dimorphic. In the present study, we investigated whether the influence of melatonin on vasotocin varies seasonally. We show that treatment of nonreproductive male green treefrogs with melatonin-filled silastic implants for 4weeks during the winter does not alter vasotocin-IR cell number in any brain region (i.e. nucleus accumbens, amygdala, preoptic area, suprachiasmatic nucleus or ventral hypothalamus). Taken together, these results suggest that the influence of melatonin on AVT is associated with sex and seasonal variation in melatonin receptor expression. We tested this hypothesis by using immunohistochemistry to characterise the distribution of melatonin receptor type 1 (MT1, also known as Mel1a) in the brain of reproductive and nonreproductive male and female frogs. We quantified MT1-IR cell number in regions known to contain AVT cell populations. Reproductive males had significantly more MT1-IR cells than nonreproductive males in all brain regions, including the combined nucleus accumbens, diagonal band of Broca and septum, striatum, amygdala, combined preoptic area and suprachiasmatic nucleus, as well as the ventral hypothalamus. In the accumbens region, where the effect of melatonin on AVT is known to be sexually dimorphic, males had significantly more MT1-IR cells than females during the summer breeding season. Based on these findings, we suggest that MT1 plays a role in mediating the interactions between melatonin and vasotocin that regulate seasonal and sexually dimorphic changes in sociosexual behaviour.