Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Is the effect of melatonin on vascular endothelial growth factor receptor-2 associated with angiogenesis in the rat ovary?

OBJECTIVES Vascular endothelial growth factor (VEGF) and its receptors play important roles in angiogenesis. Melatonin plays an important role in gonadal development; thus, its effect on the reproductive system is evident. We investigated the influence of melatonin on the expression of VEGF, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), as well as on changes in oxidative stress markers and follicle numbers in rat ovaries. METHODS For this purpose, 45 Wistar rats were separated into the following groups: Group 1, control; Group 2, vehicle; and Group 3, melatonin. Rats in Group 3 were treated with melatonin at 50 mg/kg/day for 30 days. The effects of melatonin on the expression of VEGF, VEGFR1 and VEGFR2 were established by immunohistochemistry analysis. The effects of melatonin on antioxidant enzyme activities were demonstrated by spectrophotometric analysis. RESULTS Based on immunohistochemistry analysis, VEGFR2 was predominantly localized to theca cells in the ovary. Our data indicate that melatonin treatment can significantly increase VEGF and VEGFR1 expression in the ovary ( p <0.05). Additionally, the number of degenerated follicles significantly decreased with melatonin treatment ( p <0.05). Melatonin administration also led to significant increases in antioxidant enzyme levels in the ovary. CONCLUSION Melatonin treatment exerts protective effects on follicles against increased lipid peroxidation through modulating tissue antioxidant enzyme levels. These effects may be related to angiogenesis and antioxidant activities.

A brief review about melatonin, a pineal hormone

ABSTRACT Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.

Protective effects of melatonin on spinal cord injury / Efectos protectores de la melatonina en lesión de la médula espinal

Spinal cord injury causes neuron nerve fiber loss. The aim of this study was to investigate the neuroprotective, inflammatory and angiogenetic effects of melatonin on rat spinal cord injury (SCI). For spinal cord injury, a standard weight reduction method was used that caused moderate severity of injury (100 g / cm force) at T10 Melatonin (10 mg/kg intraperitoneally ) was administered for 10 days after trauma. Each group consisted of 10 animals. of these, six were used for biochemical and four were used for the evaluation of histological analysis. Spinal cord samples were taken for histological examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity. Spinal cord injury and melatonin treated group were compared. Melatonin administration in spinal cord injury increased the activity of glial cells in the radial and funicular cells and ependymal cells and increased the activity of glial cells and also showed a positive effect on inflammation and vascular endothelial cells in synaptic connections in the nerve fibers undergoing spinal injury endothelial degeneration It is thought that it can regulate the degenerative effect which is caused by both the inflammatory effect and the angiogenic effect which will have a positive effect on the neural connection.

La lesión de la médula espinal (SCI) provoca daño en la fibra nerviosa, que puede conducir a alteraciones motoras y sensitivas, incluso la muerte. El objetivo de este estudio fue investigar los efectos neuroprotectores, proinflamatorios y proangiogénicos de la melatonina en un modelo de SCI inducida en rata. Para tal efecto se utilizaron dos grupos: Grupo 1 (n:10) se le indujo una SCI, mediante el método de reducción de peso estándar (100 g/cm fuerza), provocando una lesión de severidad moderada. Grupo 2 (n:10) inducción SCI más aplicación de T10 Melatonina (10 mg / kg v.i.) durante 10 días después del trauma. Muestras de seis animales de cada grupo fueron usados para análisis bioquímicos y los otros cuatro para la evaluación histológica. Se tomaron muestras de médula espinal para el examen histológico y para la determinación de niveles de malondialdehído (MDA) y glutatión (GSH), actividad mieloperoxidasa (MPO) y se comparó la lesión de la médula espinal y el grupo tratado con melatonina. La administración de melatonina en la lesión de la médula espinal aumentó la actividad de las células gliales en las células radiales, funiculares y ependimocitos. Ademas mostró un efecto positivo sobre la inflamación y angiogénesis en las conexiones sinápticas en las fibras nerviosas sometidas a lesión espinal. Pudiendo este participar en la regulación del efecto degenerativo causado, principalmente, por acción de angiogénesis e inflamación local.

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

ABSTRACT Objective To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. Subjects and methods We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. Results Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). Conclusions Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency.

Effects of melatonin and prolactin in reproduction: review of literature / Efeitos da melatonina e da prolactina na reprodução: revisão de literatura.

Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Resumo A glândula pineal é responsável pela produção do hormônio melatonina (MEL), sendo aceita como a glândula reguladora da reprodução em mamíferos. A prolactina (PRL) também exibe atividade reprodutiva em animais, em resposta ao fotoperíodo. Sabe-se que as concentrações de PRL são elevadas durante o verão e baixam durante o inverno, ocorrendo o oposto com os níveis do hormônio melatonina nessas estações. Nos mamíferos placentários, tanto a melatonina quanto a prolactina influenciam a implantação, que é considerada o ponto crítico da gravidez, pois o sucesso da gestação requer o desenvolvimento de uma interação sincronizada entre o endométrio e o blastocisto para o desenvolvimento da placenta. Sabe- -se ainda que os níveis de PRL durante a gestação são essenciais para a manutenção da gravidez, pois esse hormônio induz o corpo lúteo a produzir progesterona, além de estimular a implantação do blastocisto, mantendo a prenhez e o desenvolvimento placentário. Em contrapartida, tem-se demonstrado também que os níveis de melatonina no plasma aumentam durante a gestação, atingindo valores elevados no fim desse período, sugerindo que esse hormônio desempenhe um importante papel na manutenção da gestação. Dessa forma, fica claro que o tratamento com prolactina ou melatonina interfere nos processos responsáveis pelo desenvolvimento e pela manutenção da gestação.

Controladores del tiempo y el envejecimiento: núcleo supraquiasmático y glándula pineal / Aging process entrainment: suprachiasmatic nucleus and pineal gland

El núcleo supraquiasmático (NSQ) es el principal reloj biológico de los mamíferos y sincroniza la actividad de la glándula pineal al ciclo luz-oscuridad a través de una vía polisináptica. El efecto de asa de retroalimentación neuroendocrina se lleva a cabo por la melatonina. El presente trabajo pretende demostrar que la glándula pineal modula la sensibilidad a la luz en el NSQ. Se utilizaron ratas Wistar, y se asignaron a 3 grupos: grupo A (falsa pinealectomía -sham-, sin luz), grupo B (falsa pinealectomía -sham- + luz) y grupo C al cual se le realizó la pinealectomía + luz, después de la manipulación se sacrifican para realizar inmunohistoquímica para c-Fos y al final conteo celular por técnica de estereología. Se obtuvo una reducción del 46,8% del promedio de células inmunorreactivas a c-Fos en el grupo C en comparación del grupo B. Este trabajo muestra que la sensibilidad a la luz está modulada por la actividad de la glándula pineal.

The suprachiasmatic nucleus (SCN) is the main and major biological clock in mammals and is responsible for the synchronization of the pineal gland to the light/darkness cycle through a polysynaptic pathway. The neuroendocrine feedback loop effect is carried out by melatonin. This study was carried out to demonstrate that the pineal gland adjusts the sensibility to light in the suprachiasmatic nucleus. Wistar rats were allocated in 3 groups: Group A (sham pinalectomy, without light), group B (sham pinealectomy + light) and group C which underwent real pinalectomy + light. After the intervention the animals were slain to perform immunohistochemistry for c-Fos and cell counting by stereology technique. A 46.8% average reduction in c-Fos immunoreactive cells was achieved in-group C as compared with group B. The present work shows that sensibility to the light is modulate by the activity of the pineal gland.

Short-duration judgment in young Indian subjects under 30 h constant wakefulness.

The present study aimed to investigate probability of a possible endogenous circadian rhythm in human cognitive attribute to estimate short intervals. Apparently healthy young males and females were selected for our study. Eight subjects prospectively produced the short-time intervals 10 s and 60 s at 2 hourly intervals in 30 h constant routine (CR) study conducted in spring (CR-1). The study was repeated again in autumn (CR-2) in the remaining eight subjects. The established circadian markers, namely serum cortisol, salivary melatonin levels and tympanic temperature were also measured either in CR-1 or CR-2. Oral temperature was measured simultaneously. Circadian rhythms were validated in serum cortisol, salivary melatonin, oral, and tympanic temperatures. Circadian rhythm in 60 s estimates was observed in a few subjects and in all males at group level in CR-1. The cognitive attribute to perceive short intervals vary as function of season. The results provide evidence in support of interaction among the interval, circadian and circannual timing systems in human.

Melatonin: An internal signal for daily and seasonal timing.

Melatonin is secreted only during night, irrespective of the habitat of an organism and the site of its synthesis and secretion, and hence known as “darkness hormone”. Elevated melatonin levels reflect the nighttime. In vertebrates, the main site of melatonin production is the pineal gland. Species in which melatonin is also secreted from sources other than the pineal, as in some birds, relative contributions of different melatonin producing tissues to the blood melatonin level can vary from species to species. Melatonin acts through its receptors, which are members of the G protein-coupled (GPCR) superfamily. Three melatonin receptors subtypes MT1 (mel1a), MT2 (mel1b), and MT3 (mel1c) have been identified in different brain areas and other body organs of vertebrates. Melatonin synthesis and secretion are circadianly rhythmic. Changes and differences in specific features of melatonin signal can vary among species, and under a variety of natural environmental conditions. Two major physiological roles of melatonin are established in vertebrates. First, melatonin is involved in the circadian system regulated behavioural and physiological functions. Second, it is critical for the photoperiodic system. Besides, melatonin has been implicated in various ways both directly and indirectly to human health, including jet lag, sleep, immune system and cancer.

Critical time delay of the pineal melatonin rhythm in humans due to weak electromagnetic exposure.

Electromagnetic fields (EMFs) can increase free radicals, activate the stress response and alter enzyme reactions. Intracellular signalling is mediated by free radicals and enzyme kinetics is affected by radical pair recombination rates. The magnetic field component of an external EMF can delay the "recombination rate" of free radical pairs. Magnetic fields thus increase radical life-times in biological systems. Although measured in nanoseconds, this extra time increases the potential to do more damage. Melatonin regulates the body's sleep-wake cycle or circadian rhythm. The World Health Organization (WHO) has confirmed that prolonged alterations in sleep patterns suppress the body's ability to make melatonin. Considerable cancer rates have been attributed to the reduction of melatonin production as a result of jet lag and night shift work. In this study, changes in circadian rhythm and melatonin concentration are observed due to the external perturbation of chemical reaction rates. We further analyze the pineal melatonin rhythm and investigate the critical time delay or maturation time of radical pair recombination rates, exploring the impact of the mRNA degradation rate on the critical time delay. The results show that significant melatonin interruption and changes to the circadian rhythm occur due to the perturbation of chemical reaction rates, as also reported in previous studies. The results also show the influence of the mRNA degradation rate on the circadian rhythm’s critical time delay or maturation time. The results support the hypothesis that exposure to weak EMFs via melatonin disruption can adversely affect human health.

Melatonina inhibe la respuesta de cortisol a ACTH: posible mediación a través del gen reloj Per1 / Melatonin inhibition of the cortisol response to ACTH may be exerted through period circadian protein homolog 1 (Per1)

Background: Circadian cortisol production results from the interaction of the circadian production of ACTH, the autonomic nervous system and intrinsic factors within the gland. An additional regulator is the neuro-hormone melatonin. In human adrenal gland cultures, melatonin inhibited ACTH stimulated cortisol production and Per1 mRNA expression. ACTH actions on the adrenal involve early and late responses. Aim: To investigate the effects of melatonin on the time course of ACTH stimulated cortisol production and of Per1 expression in the lamb adrenal gland. Material and Methods: Adrenal glands and plasma of five newborn lambs were obtained. Adrenal glands were cut in 15 mg explants. Three of these explants were stored for RNA extraction. The rest of explants were using in different culture protocols with ACTH and melatonin. Results: Lambs had an in vivo a circadian variation in plasma cortisol and in adrenal Per1 expression. In vitro, ACTH stimulated an early and late increase in cortisol production and an early increase in Per1 expression reaching a maximum at 3 hours of treatment. Melatonin inhibited the early Per1 response to ACTH without affecting the early ACTH stimulated cortisol production. However, melatonin inhibited the late response of cortisol production to ACTH. Conclusions: The inhibitory actions of melatonin on Per1 response to ACTH may contribute to the inhibitory effects of melatonin on adrenal steroidogenic response to ACTH.

Effects of ischemia/reperfusion on beta cells of pancreas and protective effects of melatonin treatment / Efectos de la isquemia/reperfusión sobre células beta del páncreas y efectos protectores del tratamiento de melatonina

Oxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia-reperfusion (I/R). In this study, we investigated the putative protective effects of melatonin treatment on pancreatic I/R injury. Sprague Dawley male rats were subjected to 30 min of pancreatic pedicle occlusion followed by 90 min reperfusion. Melatonin (10 mg/kg. s.c) was administrated 30 min prior to ischemia or I/R application. At the end of the reperfusion periods, rats were decapitated. Pancreatic samples were taken for transmission electron microscopy. The results indicated that ischemia created b cell damage as evidenced by dilatation between the nucleus inner and outer membrane and degeneration on islets of Langerhans cells, was reversed by melatonin treatment. As melatonin administration reversed these microscopic damage, it seems likely that melatonin protects pancreatic tissue against oxidative damage.

Los radicales libres del oxígeno son considerados como uno de los componentes más importantes que participan en las alteraciones fisiopatológicas del tejido durante la isquemia-reperfusión (I/R). En este estudio, se investigó el supuesto efecto protector del tratamiento de melatonina sobre la lesión pancreática I/R. Ratas Sprague Dawley machos fueron sometidas a 30 minutos de oclusión del pedículo pancreático seguido de 90 minutos de reperfusión. La melatonina (10 mg/kg) fue administrada 30 minutos antes de la isquemia o de la aplicación I/R. Al finalizar los periodos de reperfusión, las ratas fueron decapitadas. Fueron tomadas muestras pancreáticas para el análisis en microscopía electrónica de transmisión. Los resultados indicaron que la isquemia ocasionó daño en las células beta demostrado por la dilatación entre el núcleo interior y la membrana exterior y la degeneración de los islotes de células pancreáticas, los que fueron revertidos por el tratamiento de melatonina. Como la administración de melatonina revirtió estos daños microscópicos, parece probable que ella proteja al tejido pancreático contra el daño oxidativo.

Morphologic changes in rat's pineal gland after eliminating retinal photic stimulation / Cambios morfológicos en la glándula pineal de ratas luego de la eliminación de la estimulación fótica retiniana

Melatonin secretion from mammalian pineal glands is regulated by light stimulation by means of a complex neuroanatomical pathway that includes the retina, hypothalamic suprachiasmatic nucleus, intermediolateral nucleus of the thoracic spinal cord, and finally, the superior cervical ganglia. The purpose of this study was to analyze the changes in the pinealocytes and the blood vessel density of the pineal gland after eliminating photic stimulation in rats. Thirteen adult Sprague-Dawley rats were divided into 2 groups, Group I acted as control, and Group II was subjected to a retinal lesion, by means of alcohol injected bilaterally to both ocular bulbs. After 3 weeks, the glands of both groups were processed with hematoxilin-eosin (HE) and observed with an optic microscope. Group II results presented higher values in the number of pinealocytes and in the blood vessels observed. The differences with Group I was significant at p <0.01. These results give an indirect evidence of the effect that photic stimulation suppression has in the pineal gland in rats.

La secreción de melatonina por parte de glándula pineal de los mamíferos es regulada por la estimulación luminosa mediante complejas vías neuro anatómicas que incluyen la retina, el núcleo supraquiasmático hipotalámico, el núcleo intermediolateral de la médula torácica y finalmente el ganglio cervical superior. El propósito de este estudio fue analizar los cambios en la densidad de pinealocitos y vasos sanguíneos de la glándula pineal, luego de eliminar la estimulación fótica en ratas. Se utilizaron 13 ratas adultas Sprague Dawley divididas en 2 grupos, Grupo I actuó como control, y el Grupo II fue sometido a una lesión retiniana, por medio de alcoholización bilateral de ambos bulbos oculares. Luego de tres semanas las glándulas de ambos grupos fueron procesadas para hematoxilina-eosina y observadas al microscopio óptico. El grupo II presentó valores mayores en el número de pinealocitos y de vasos sanguíneos observados, las diferencias con el Grupo I fueron significativas con p<0.01. Estos resultados entregan una evidencia indirecta del efecto que la supresión de la estimulación fótica tiene en la glándula pineal en ratas.

Efeitos da melatonina no sistema genital feminino: breve revisão / Melatonin effects on the female genital system: a brief review

A melatonina é um hormônio produzido pela glândula pineal, cuja secreção está diretamente relacionada ao ciclo claro-escuro. É um poderoso antioxidante e tem papel fundamental na regulação do estado sono/vigília, do ritmo de vários processos fisiológicos, participando do controle do relógio biológico, inclusive nos seres humanos. Ressalta-se que há evidências da sua ação no sistema genital feminino, influenciando a função ovariana e a fertilidade. De fato, este hormônio interage com esteróides sexuais, como o estrogênio, modificando a sinalização celular e a resposta no tecido alvo. Estudos clínicos sugerem que o tratamento com a melatonina interviria com a evolução de neoplasia-dependente do estrogênio. O objetivo dessa revisão é analisar as principais ações da melatonina no sistema neuroendócrino, no ciclo sono-vigília, no sistema imunológico, no sistema cardiovascular, bem como no sistema reprodutor.

Melatonin is secreted by the pineal gland and this is linked to the day/night cycle. It is an antioxidant and plays a fundamental role in the regulation of the jet-lag stage, in several physiological reactions and in control of the biologic rhythm. Human melatonin has an important influence on the female genital system. In fact, melatonin may influence production and action of steroids, modifying cellular signalization on the target tissue. There are many evidences that the melatonin therapy may be interfering with neoplasia development, mainly of the estrogen-dependent tumor. This paper aims to analyze the actions of melatonin on the neuroendocrine, immunological and cardiovascular systems, as well as on the reproductive function.

In vitro effects of steroid hormones on arylalkylamine N-acetyltransferase (AA-NAT) activity in the pineal of fish, Clarias gariepinus (Burchell, 1822) during different phases of breeding cycle.

In vitro effects of gonadal hormones (testosterone, 17beta-estradiol estriol and estrone) and corticosteroid hormones (corticosterone and cortisol) were studied on arylalklyamine N-acetyltransferase (AA-NAT) activity in the pineal organ of the fish, C. gariepinus during quiescent, progressive, breeding and regressive phases of its annual breeding cycle. The pineals were collected under dim red light, maintained in organ culture for 7 hr and incubated with three concentrations (10(-6), 10(-5) and 10(-4) M) of hormones for 6 hr. The treatments with gonadal hormones and corticosteroid hormones inhibited pineal AA-NAT activity in a dose-dependent manner during all the phases of the breeding cycle. AA-NAT activity was comparatively more sensitive to the inhibitory effects of the gonadal hormones during the regressive phase and less sensitive during the quiescent phase. Further, the enzyme activity was more sensitive to the inhibitory effects of corticosteroid hormones (corticosterone and cortisol) during the breeding phase and less sensitive during the quiescent phase. These findings seem to suggest that gonadal hormones and corticosteroid hormones have direct inhibitory influence on AA-NAT activity and, hence melatonin synthesis in the photoreceptive pineal organ of C. gariepinus.

Triiodothyronine and melatonin influence antioxidant defense mechanism in a teleost Anabas testudineus (Bloch): in vitro study.

The effect of the hormones triiodothyronine (T3) and melatonin on antioxidant defense system was studied in 6-propyl thiouracil (6-PTU)-treated or photoperiod-exposed teleost Anabas testudineus. 6-PTU (2 microg/g) treatment or photoperiod exposure (24 h) increased malondialdehyde (MDA) and conjugated dienes (CD) concentrations, indicating increased lipid peroxidation (LPO) in the experimental conditions. T3 or melatonin (10(-6) M) treatment for 15 min in vitro in PTU-treated fish reversed the activity of superoxide dismutase (SOD), catalase and glutathione content. T3-treated group showed no change in glutathione peroxidase (GPx) activity, whereas melatonin treatment decreased its activity. T3 inhibited glutathione reductase (GR) activity. Photoperiod exposure (physiological pinealotomy) induced a stressful situation in this teleost, as evidenced by LPO products and antioxidant enzyme activities. Melatonin and T3 treatment for 15 min in vitro also reversed the effect of photoperiod on peroxidation products and the SOD and catalase activities. GR activity decreased in photoperiod-exposed group and melatonin and T3 treatment reversed the activities. The antioxidant enzymes responded to the stress situation after 6-PTU treatment and photoperiod exposure by altering their activities. The study suggested an independent effect of T3 and melatonin on antioxidant defence mechanism in different physiological situations in fish.

Nocturnal plasma levels of melatonin in quails (Coturnix japonica) injected with l-5-hydroxy-tryptophan

This study aimed to demonstrate the influence of the systemic administration of l-5-hydroxy-tryptophan (L-HTP) on the plasma levels of melatonin during the dark period in quails. Throughout daylight, the plasma levels of melatonin did not differ significantly, oscillating between 110.2 ± 15.8 pg.mL-1 and 157.4 ± 34.8 pg.mL-1, from 8 to 16 hours. L-HTP (25 mg.kg-1, through the intracelomic route) administered at 18 hours lessened significantly the nocturnal increase of the plasma levels of melatonin (controls, 327.3 ± 20.1 and 315.8 ± 20.9 pg.mL-1 vs. 242.1 ± 24.8 and 217.5 ± 21 pg.mL-1, respectively, at 20 and 24 hours, P < 0.05). The results obtained showed that the administration of LHTP reduced the nocturnal melatonin release, possibly by bringing about an increase in serotonin synthesis and synaptic release in the pineal. Therefore, the serotoninergic transmission from the raphe towards the pineal would constitute a mechanism of modulation of the synthesis and melatonin release in quails.

Este trabalho objetivou demonstrar a influência da administração sistêmica de l-5-hidroxi-triptofano (L-HTP) sobre os níveis plasmáticos de melatonina durante o período noturno em codornas. Ao longo do período claro, os níveis plasmáticos de melatonina não diferiram significativamente, oscilando entre 110,2 ± 15,8 pg.mL-1 e 157,4 ± 34,8 pg.mL-1, de 8 às 16 horas. L-HTP (25 mg.kg-1, via intracelomática), administrado às 18 horas atenuou significativamente a elevação noturna dos níveis plasmáticos de melatonina (controles, 327,3 ± 20,1 e 315,8 ± 20,9 pg.mL-1 vs. 242,1 ± 24,8 e 217,5 ± 21 pg.mL-1, respectivamente, às 20 e 24 horas, P < 0,05). Os resultados obtidos mostraram que a administração de L-HTP reduziu a liberação noturna de melatonina, possivelmente por suscitar um aumento da síntese e liberação sináptica de serotonina na pineal. Portanto, a transmissão serotoninérgica da rafe para a pineal constituiria um mecanismo de modulação da síntese e/ou liberação de melatonina em codornas.

Partial suppressive effect of melatonin on indomethacin-induced renal injury in rat.

Intramuscular injection of a single high dose of indomethacin (20 mg/kg) in fasted rats produced renal injury. The results showed increases in the level of lipid peroxidation and cholesterol, and activity of acid phosphatase and alkaline phosphatase in the kidney. Also, the renal contents of both reduced glutathione and activity of total adenosine triphosphatase were decreased by the toxicant. In serum, indomethacin increased activity of lactate dehydrogenase and acid phosphatase, and levels of creatinine and inorganic phosphorus. Paradoxically, administration of melatonin (0.75 mg/rat/day) alone for 7 days decreased significantly the activity of lipid peroxidation and acid phosphatase, and increased, but not significantly, the level of reduced glutathione in the kidney. Also, serum level of creatinine tended to decrease, but not significantly. Pretreatment with melatonin prevented the increase by subsequently administered indomethacin in the renal activity of lipid peroxidation and acid phosphatase. However, this pretreatment regimen partially suppressed the adverse changes in the remaining analyzed cytotoxic parameters induced by indomethacin in both serum and kidney. These results indicate that oral administration of melatonin at a low dose level exerted moderate antioxidant action, thereby it protected against some of the renal detrimental effects produced by indomethacin.

Evaluation of the implantation in pinealectomized and/or submitted to the constant illumination rats

En este trabajo evaluamos los aspectos morfológicos y cuantitativos de los sitios de implantaciones en úteros de ratas pinealectomizadas y/o sometidas a iluminación constante. Los grupos experimentales fueron: I í ratas normales mantenidas en ciclo claro / oscuro de 12/12 horas, durante dos meses, cruzadas y sacrificadass en el 60 día de pre¤ez (control); II í ratas sham-pinealectomizadas mantenidas en ciclo claro/oscuro de 12/12 horas, durante dos meses, cruzadas y sacrificadas en el 60 día de pre¤ez (control); III í ratas pinealectomizadas mantenidas en ciclo claro/oscuro de 12/12 horas, durante dos meses, cruzadas y sacrificadas en el 60 día de pre¤ez; IV í ratas normales mantenidas en constante iluminación durante dos meses acasaladas y sacrificadas en el 60 día de pre¤ez; V í ratas sham-pinealectomiazadas mantenidas en constante iluminación durante dos meses, cruzadas y sacrificadas en el 60 día de pre¤ez; VI í ratas pinealectomizadas, mantenidas en constante iluminación durante dos meses, cruzadas y sacrificadas en el 60 día de pre¤ez. El análisis estadístico de las medias de los sitios de implantaciones mostró que hubo diferencia significativa, donde los grupos III, IV, V y VI diferían de los grupos I y II, los cuales presentaron las mayores medias. Los grupos III, IV, V y VI no son diferentes entre sí. El análisis morfológico de los sitios en los grupos controles reveló la presencia de peque¤as lagunas conteniendo sangre, además de células trofoblásticas y algunos citrofoblastos poliploides. En los grupos III, IV, V y VI se evidenció lagunas muy desarrolladas en los sitios, con trofoblastos, citrofoblastos con alto grado de poliploidia y sinciciotrofoblastos. Concluimos que la pinealectomía y/o constante iluminación llevan a una reducción del número de blastocistos implantados en ratas, además estimula el desarrollo de los sitios de implantación, indicando así; que la melatonina puede tener importante función en la viabilidad de implantación del blastocisto.