Increased Melatonin Secretion Research Articles

АНАЛІЗ СМАКО-АРОМАТИЧНИХ ВЛАСТИВОСТЕЙ НОВИХ КАВОЗАМІННИХ ПРОДУКТІВ ІЗ СОЛОДОВОЇ СИРОВИНИ

Caffeine has a negative effect on human health, but the withdrawal from caffeine should be gradual. Thus, caffeine is a nonspecific inhibitor of adenosine receptors and prevents increased melatonin secretion during the dark hours of the day and affects other parameters of human sleep. The article analyzes the feasibility of introducing coffee into the diet to gradually reduce the amount of caffeine consumed. The relevance of the study is added by the stable growth of the coffee market in recent years. The purpose of the study is a scientific and practical justification for improving the organoleptic properties of modern coffee drinks through the use of malt, followed by comparison of different recipes for organoleptic characteristics. The research methodology included the preparation of three types of coffee beverages from different types of malt in a special laboratory reactor system IKA LR-2. ST Starvisc 200 and sensory analysis by a group of five respondents of different ages and genders, also analyzed their taste properties compared to beverages with chicory. Studies have shown that malt raw materials can improve the properties that roasted barley is inferior to chicory and natural coffee, because malt raw materials can improve the color, aroma, bitterness and aftertaste. At the same time, a weak grain taste and malty sweetness were recorded in the drinks. These figures are due to the increased proportion of simple sugars, which pass well into the solution during extraction. Malt is characterized by a high content of low molecular weight compounds, such as amino acids and simple sugars. Those biologically active components that did not participate in the formation of color compounds have a high rate of extractives and in large quantities pass into the finished drink, improving its biological activity. As a result, these compounds play a significant role in the roasting of malt, as they form both colored and aromatic compounds. That is why coffee drinks based on malt are among the promising types of modern coffee drinks.

Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis

Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.

Effects of Cataract Surgery on Melatonin Secretion in Adults 60 Years and Older

Cataract surgery, which increases perception of light, may increase melatonin secretion. Melatonin secretion has been associated with depression, diabetes, cognitive impairment, and breast cancer. To date, no evidence from a randomized clinical trial exists to support this cataract surgery hypothesis. To determine whether cataract surgery modifies the melatonin secretion at 3 months after cataract surgery in 169 adult patients. A parallel-group randomized clinical trial was conducted at a single referral center from July 1, 2014, to June 30, 2017. Data were analyzed from January 1, 2018, to March 31, 2019. Patients were aged 60 years or older, had no history of cataract surgery, and had cataracts with grade 2 or higher nuclear opacifications based on the Lens Opacities Classification System III. Analyses were based on intention to treat. Patients were randomized 1:1:1:1 to receive cataract surgery using artificial clear intraocular lens (IOL) or yellow IOL. Group 1 received prompt surgery with clear IOL, group 2, prompt surgery with yellow IOL, group 3, delayed surgery with clear IOL, and group 4, delayed surgery with yellow IOL. The intervention group consisted of groups 1 and 2, and the control group consisted of groups 3 and 4. Urinary melatonin excretion in the intervention group was measured at 3 months after surgery, and urinary melatonin excretion in the control group was measured before delayed surgery. Of the 169 randomized patients, 97 were men (57.4%). The mean (SD) age was 75.7 (6.7) years. Mean urinary melatonin excretion was calculated as standardized urinary concentration, the ratio of urinary concentration to urinary creatinine concentration (nanograms per milligram of creatinine), in the intervention group after cataract surgery. Mean urinary melatonin excretion was significantly higher than in the control group (adjusted mean difference of creatinine concentration, 0.159 log ng/mg, 95% CI, 0.045-0.273; P = .007) independent of baseline urinary melatonin excretion and potential confounders. Subgroup analysis comparing group 1 with group 3 revealed that concentration of urinary melatonin excretion in patients who received clear IOLs was higher than the control group by creatinine concentration 0.212 log ng/mg (95% CI of the difference, 0.058-0.365; P = .008). However, the difference between patients in group 2 and group 4 was not significant (adjusted mean difference for creatinine excretion, 0.083 log ng/mg, 95% CI, -0.087 to 0.253; P = .33). The difference of concentration of mean urinary melatonin excretion between patients in group 1 and those in group 2 was not significant (95% CI of the difference for creatinine concentration, -0.19 to 0.40 log ng/mg; P = .48). The findings in this study support the hypothesis that cataract surgery increases melatonin secretion. The effect of clear IOLs vs yellow IOLs on these outcomes was not shown to be different. UMIN-CTR Identifier: UMIN000014559.

The blood, by night and day

Stem Cells Many developmental events have now been associated with the daily cycle. But what is happening physiologically during the hours of light and dark? Bone turnover, immunity, and stem cell migration from the bone marrow are certainly affected. Golan et al. observed two peaks in bone marrow hematopoietic stem and progenitor cells (HSPCs) after transient increases of norepinephrine and tumor necrosis factor. The nighttime peak increases melatonin secretion to maintain and replenish HSPCs and to reduce differentiation. By contrast, the morning peak increases differentiation and vascular permeability for blood replenishment. Hence, light and dark provide different signals that are crucial for blood cell activity and overall health. Cell Stem Cell 10.1016/j.stem.2018.08.002 (2018).

Daily Onset of Light and Darkness Differentially Controls Hematopoietic Stem Cell Differentiation and Maintenance

Hematopoietic stem and progenitor cells (HSPCs) tightly couple maintenance of the bone marrow (BM) reservoir, including undifferentiated long-term repopulating hematopoietic stem cells (LT-HSCs), with intensive daily production of mature leukocytes and blood replenishment. We found two daily peaks of BM HSPC activity that are initiated by onset of light and darkness providing this coupling. Both peaks follow transient elevation of BM norepinephrine and TNF secretion, which temporarily increase HSPC reactive oxygen species (ROS) levels. Light-induced norepinephrine and TNF secretion augments HSPC differentiation and increases vascular permeability to replenish the blood. In contrast, darkness-induced TNF increases melatonin secretion to drive renewal of HSPCs and LT-HSC potential through modulating surface CD150 and c-Kit expression, increasing COX-2/αSMA+ macrophages, diminishing vascular permeability, and reducing HSPC ROS levels. These findings reveal that light- and darkness-induced daily bursts of norepinephrine, TNF, and melatonin within the BM are essential for synchronized mature blood cell production and HSPC pool repopulation.

Melatonin inhibits hypothalamic gonadotropin-releasing hormone release and reduces biliary hyperplasia and fibrosis in cholestatic rats.

Melatonin is a hormone produced by the pineal gland with increased circulating levels shown to inhibit biliary hyperplasia and fibrosis during cholestatic liver injury. Melatonin also has the capability to suppress the release of hypothalamic gonadotropin-releasing hormone (GnRH), a hormone that promotes cholangiocyte proliferation when serum levels are elevated. However, the interplay and contribution of neural melatonin and GnRH to cholangiocyte proliferation and fibrosis in bile duct-ligated (BDL) rats have not been investigated. To test this, cranial levels of melatonin were increased by implanting osmotic minipumps that performed an intracerebroventricular (ICV) infusion of melatonin or saline for 7 days starting at the time of BDL. Hypothalamic GnRH mRNA and cholangiocyte secretion of GnRH and melatonin were assessed. Cholangiocyte proliferation and fibrosis were measured. Primary human hepatic stellate cells (HSCs) were treated with cholangiocyte supernatants, GnRH, or the GnRH receptor antagonist cetrorelix acetate, and cell proliferation and fibrosis gene expression were assessed. Melatonin infusion reduced hypothalamic GnRH mRNA expression and led to decreased GnRH and increased melatonin secretion from cholangiocytes. Infusion of melatonin was found to reduce hepatic injury, cholangiocyte proliferation, and fibrosis during BDL-induced liver injury. HSCs supplemented with BDL cholangiocyte supernatant had increased proliferation, and this increase was reversed when HSCs were supplemented with supernatants from melatonin-infused rats. GnRH stimulated fibrosis gene expression in HSCs, and this was reversed by cetrorelix acetate cotreatment. Increasing bioavailability of melatonin in the brain may improve outcomes during cholestatic liver disease.NEW & NOTEWORTHY We have previously demonstrated that GnRH is expressed in cholangiocytes and promotes their proliferation during cholestasis. In addition, dark therapy, which increases melatonin, reduced cholangiocyte proliferation and fibrosis during cholestasis. This study expands these findings by investigating neural GnRH regulation by melatonin during BDL-induced cholestasis by infusing melatonin into the brain. Melatonin infusion reduced cholangiocyte proliferation and fibrosis, and these effects are due to GNRH receptor 1-dependent paracrine signaling between cholangiocytes and hepatic stellate cells.

Twice Daily Melatonin Peaks in Siberian but not Syrian Hamsters under 24 h Light:Dark:Light:Dark Cycles

The daily pattern of blood-borne melatonin varies seasonally under the control of a multi-oscillator circadian pacemaker. Here we examine patterns of melatonin secretion and locomotor activity in Siberian and Syrian hamsters entrained to bimodal LDLD8:4:8:4 and LD20:4 lighting schedules that facilitate novel temporal arrangements of component circadian oscillators. Under LDLD, both species robustly bifurcated wheel-running activity in distinct day scotophase (DS) and night scotophase (NS) bouts. Siberian hamsters displayed significant melatonin increases during each scotophase in LDLD, and in the single daily scotophase of LD20:4. The bimodal melatonin secretion pattern persisted in acutely extended 16 h scotophases. Syrian hamsters, in contrast, showed no significant increases in plasma melatonin during either scotophase of LDLD8:4:8:4 or in LD20:4. In this species, detectable levels were observed only when the DS of LDLD was acutely extended to yield 16 h of darkness. Established species differences in the phase lag of nocturnal melatonin secretion relative to activity onset may underlie the above contrast: In non-bifurcated entrainment to 24 h LD cycles, Siberian hamsters show increased melatonin secretion within ∼2 h after activity onset, whereas in Syrian hamsters, detectable melatonin secretion phase lags activity onset and the L/D transition by at least 4 h. The present results provide new evidence indicating multi-oscillator regulation of the waveform of melatonin secretion, specifically, the circadian control of the onset, offset and duration of nocturnal secretion.

Short-term effects of melatonin and pinealectomy on serotonergic neuronal activity across the light–dark cycle

Melatonin (MLT) and serotonin (5-HT) are two biosynthetically related compounds implicated in several common physiological functions and the etiology of mood disorders. How they interact, though, is not yet fully understood. In this study, single-unit extracellular recordings were used to monitor dorsal raphe nucleus (DR) 5-HT neuronal activity in anesthetized rats, under basal conditions (CTRL), in response to MLT administration, and after pinealectomy (PX) across the light-dark cycle. Under basal conditions, the number of spontaneously active 5-HT neurons and their firing rate were both significantly lower in the dark phase. In the light phase, administration of MLT at low doses (0.5-1 mg/kg, i.v.) decreased 5-HT firing activity. This inhibitory effect of MLT was completely blocked by the MT₁/MT₂ receptor antagonist luzindole, but not by the selective MT(2) receptor antagonist 4P-PDOT, the selective 5-HT(1A) receptor antagonist WAY100635, or by the α₂ adrenoceptor antagonist idazoxan. In the opposite experiment, PX increased 5-HT firing activity in the dark phase, and this was reversed by MLT administration (1 mg/kg, i.v.). Finally, in a forced swim test, MLT (1 mg/kg, i.p.) increased immobility time and decreased swimming behavior. Together, these results suggest that nocturnal MLT secretion imposes tonic inhibitory control over a sub-population of DR 5-HT neurons. This MLT-induced decrease in 5-HT neurotransmission may represent a biological mechanism underlying mood disorders characterized by increased MLT secretion, such as seasonal affective disorder.

Effects of orexigenic peptides and leptin on melatonin secretion during different photoperiods in seasonal breeding ewes: An in vitro study

The pineal gland (PG) acts as a neuroendocrine transducer of daily and seasonal time through the nocturnal release of melatonin. Here, we examined the interaction of season, orexin, ghrelin, and leptin on melatonin secretion by pineal explants in short-term culture. Glands were collected after sunset from 12 ewes during long days (LD; April and May) and from an additional 12 ewes during short days (SD; October and November). Glands were transected sagittally into strips, with each equilibrated in 2.5 mL of Dulbecco's modified Eagle's medium for 60 min, followed by a 2-h incubation in control medium or medium containing orexin B (10 and 100 ng/mL), ghrelin (10 and 100 ng/mL), or 50 ng/mL of leptin. After a 3-h incubation, some PG explants treated previously with lower doses of orexin or ghrelin were challenged with 50 ng/mL of leptin and those treated with both doses of orexin were challenged with 300 nM of the β-agonist isoproterenol. One milliliter of medium was harvested and replaced from each well every 30 min. Treatment with the low dose of orexin during LD increased melatonin secretion about 110% ( P < 0.01); treatment with a high dose increased melatonin secretion about 47% ( P < 0.001). During the SD period, leptin stimulated ( P < 0.05) melatonin secretion slightly compared with mean melatonin concentration in controls. However, together, orexin and leptin depressed ( P < 0.01) melatonin secretion. Both doses of ghrelin reduced ( P < 0.01) melatonin concentration during the SD season compared with control culture. Addition of ghrelin and leptin to culture medium increased ( P < 0.01) melatonin concentration compared with ghrelin-treated culture and decreased melatonin concentration ( P < 0.01) compared with leptin-treated culture during SD. Isoproterenol stimulated ( P < 0.01) melatonin secretion compared with values observed during the pretreatment period. We conclude that orexigenic peptides (orexin B and ghrelin) and an anorectic peptide (leptin) affect PG directly. The responses of PG to those hormones depend on day length. Moreover, secretion of melatonin from the ovine PG is under an adrenergic regulation.

Longitudinal Associations between Endogenous Melatonin Production and Reported Sleep Duration from Childhood to Early Adulthood

Background/Aims: The study objective was to assess longitudinal associations between melatonin secretion and reported sleep duration from childhood to early adulthood. Methods: In the frame of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, 24-hour melatonin secretion and average daily sleep duration were determined once during childhood (4–< 11 years), adolescence (11–<16 years) and early adulthood (16–19 years) in 52 participants (23 males/29 females) aged 4–19 years. The associations between (1) melatonin secretion and sleep duration in childhood (cross-sectional); (2) melatonin secretion in childhood and sleep duration in early adulthood (prospective), and (3) changes in melatonin secretion and concurrent changes in sleep duration from childhood to early adulthood (concurrent) were analyzed. Results: Melatonin secretion was associated with sleep duration in childhood (cross-sectional, 3.5 min/day/10 µg 6-hydroxymelatonin sulfate (6-OHMS)/day, p = 0.009) and tended to predict sleep duration in early adulthood (prospective, 9.8 min/day/10 µg 6-OHMS/day, p = 0.09). An individual increase in melatonin secretion between childhood and early adulthood was associated with a concurrent increase in sleep duration (concurrent, 6.9 min/day/10 µg 6-OHMS/day, p = 0.046). Conclusion: Our observational data suggest that pineal production of melatonin in childhood is correlated with alterations in sleep duration until early adulthood. Nevertheless, this observational evidence needs to be verified in clinical studies.

‘TRPing’ Synaptic Ribbon Function in the Rat Pineal Gland: Neuroendocrine Regulation Involves the Capsaicin Receptor TRPV1

Synaptic ribbons (SRs) are presynaptic structures thought to regulate and facilitate multivesicular release. In the pineal gland, they display a circadian rhythm with higher levels at night paralleling melatonin synthesis. To gain more insight into the processes involved and the possible functions of these structures, a series of experiments were conducted in rodents. We studied the regional distribution of a molecular marker of pineal SRs, the kinesin motor KIF3A in the gland. Respective immunoreactivity was abundant in central regions of the gland where sympathetic fibers were less dense, and vice versa, revealing that intercellular communication between adjacent pinealocytes is enhanced under low sympathetic influence. KIF3A was found to be colocalized to the transient receptor potential channel of the vanilloid receptor family, subtype 1 (TRPV1). The TRPV1 agonist capsaicin increased melatonin secretion from perifused pineals in a dose-dependent manner that was blocked by the competitive TRPV1 antagonist capsazepine. No change in free intracellular calcium was observed in response to TRPV1 ligands applied to pinealocytes responding to norepinephrine, bradykinin and/or depolarization. These data clearly indicate that TRPV1 actively regulates pineal gland function.

The Effects of PACAP and VIP on the in Vitro Melatonin Secretion from the Embryonic Chicken Pineal Gland

The effects of in vitro VIP administration and those of in ovo pretreatment with PACAP antagonist (PACAP6-38) on the development of the embryonic melatonin (MT) secretion were investigated. With dynamic in vitro bioassay we showed that (1) the development of the circadian MT secretion seems to be unaffected by VIP administrations or by PACAP6-38 pretreatments; (2) exposure of the embryonic chicken pineal gland to VIP induces transitory increase in MT secretion at or before the 14th embryonic day in vitro.

Development of the Circadian Melatonin Rhythm and Its Responsiveness to PACAP in the Embryonic Chicken Pineal Gland

The embryonic development of the circadian melatonin (MT) rhythm and the responsiveness of embryonic MT secretion to pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated. Using dynamic in vitro bioassays, we showed the following: (1) The circadian clock and/or the intracellular signal transduction pathways connecting the clock to the MT synthesizing apparatus appear between days 16 and 18 (E16-18) of embryonic development. Lack of periodical environmental stimuli can lead to a delay in this maturation. (2) Exposure of the embryonic chicken pineal gland to PACAP induces a transitory increase in MT secretion and (3) a transitory increase in cyclic AMP efflux at or before day E13 in vitro.

Development of the circadian melatonin rhythm and the effect of PACAP on melatonin release in the embryonic chicken pineal gland. An in vitro study

Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to participate in modulation of circadian rhythm and to stimulate melatonin (MT) secretion in both the rat and chicken pineal glands. In contrast to mammals, the main regulator of circadian rhythm in birds is the pineal gland, which begins its rhythmic MT production already during embryonic life. In the present study, we investigated the development of MT secretion in explanted embryonic chicken pineals and their responsiveness to PACAP in a perifusion system. Our results show that: (1) the circadian clock and/or the intracellular signal transduction system connecting the clock to MT synthesizing apparatus develop between the embryonic days 16–18 (E16–18), even in vitro. (2) Exposure of the embryonic chicken pineal gland to PACAP induces transitory increase in MT secretion but does not induce visible phase shift in the circadian rhythm. (3) Cyclic AMP (cAMP) efflux also responds to PACAP at or before day E13 in embryonic chicken pineal gland in vitro.

Secretion of melatonin in healthy elderly subjects: a longitudinal study.

We report on a 10-year longitudinal study on 24-h serum melatonin secretion (AUC) in healthy human subjects. Fifty women and 53 men (aged 42-83 yr) participated in the study initially. Of these, 18 women and 15 men were followed for 6 consecutive years. (a) Cross-sectional analysis (n = 103): A significant (R = -.49, P =.0001) decline in AUC melatonin with age was found in women, but not in men. (b) Longitudinal analysis (n = 33): Repeated-measure ANOVAs for women (n = 18): Time: linear F(1,17) = 5.14, P =.037. The AUC increased by about 40% over the six-year period. In men, there were no significant changes. In agreement with most cross-sectional studies, an inverse relationship was found between melatonin secretion and age. However, the longitudinal study showed an increase in melatonin secretion, indicating the presence of putative compensatory mechanisms during healthy aging. Changes in melatonin secretion were gender specific, occurring in women only.

Melatonin and methimazole mimic short-day-induced fattening in gray mouse lemurs

Short-day-induced fattening was investigated in the small nocturnal primate Microcebus murinus. Animals were either transferred from long photoperiod (LP) to short photoperiod (SP) or maintained in LP and submitted to various treatments. Animals fed daily on 40 μg of melatonin (MEL) at two different times showed a significant increase in body mass compared to LP-exposed animals. This weight gain was more marked in animals fed with MEL 2 h before night onset, suggesting a critical period around the first hours of the night. The MEL-induced fattening was associated with an increase in food intake and a decrease in plasma thyroxin (T4) levels. On the other hand, a decrease in T4 plasma levels induced by two doses of methimazole (MET) led to either an increase (3 mg/day) or a decrease (10 mg/day) of body mass, suggesting a role of thyroid hormones in the photoperiodic regulation of body mass. The MET-induced fattening did not involve any change in food intake. These findings suggest that autumn fattening in the gray mouse lemur proceeds from two distinct mechanisms. First, an increase of food intake may result in the SP-induced increase in MEL secretion. Second, a decrease of energy expenditure may be due to the MEL-induced hypothyroidism.

Effects of Diazepam and Its Metabolites on Nocturnal Melatonin Secretion in the Rat Pineal and Harderian Glands. A Comparative In Vivo and In Vitro Study

We investigated the effects of diazepam (DZP) and its three metabolites: nordiazepam (NZP), oxazepam (OZP), and temazepam (TZP) on pineal gland nocturnal melatonin secretion. We looked at the effects of benzodiazepines on pineal gland melatonin secretion both in vitro (using organ perifusion) and in vivo in male Wistar rats sacrificed in the middle of the dark phase. We also examined the effects of these benzodiazepines on in vivo melatonin secretion in the Harderian glands. Neither DZP (10−5–10−6 M) nor its metabolites (10−4–10−5 M) affected melatonin secretion by perifused rat pineal glands in vitro. In contrast, a 10−4 M suprapharmacological concentration of DZP increased melatonin secretion of perifused pineal glands by 70%. In vivo, a single acute subcutaneous administration of DZP (3 mg/kg body weight) significantly affected pineal melatonin synthesis and plasma melatonin levels, while administration of the metabolites under the same conditions did not. DZP reduced pineal melatonin content (−40%), N-acetyltransferase activity (−70%), and plasma melatonin levels (−40%), but had no affects on pineal hydroxyindole-O-methyltransferase activity. Neither DZP nor its metabolites affected Harderian gland melatonin content. Our results indicate that the in vivo inhibitory effect of DZP on melatonin synthesis is not due to the metabolism of DZP. The results also show that the control of melatonin production in the Harderian glands differs from that observed in the pineal gland.

Does hepatic metabolism of melatonin affect the endogenous serum melatonin level in man?

Melatonin (MT) is metabolized in the liver by cytochrome P450 (CYP) 1A2 but its importance for the metabolic process has not been fully elucidated. Therefore, the objective of this investigation was to study whether patients with different CYP1A2 activity would have different nocturnal serum MT levels. For that purpose serum MT concentrations were determined every second hour during the night in 12 healthy subjects and their MT areas under the curve (MT-AUCs) were calculated. Caffeine (CA) clearance was determined in advance. It is generally accepted that CA clearance reflects CYP1A2 activity. This made it possible to evaluate whether a relationship prevails between endogenous MT-AUCs and CYP1A2 activity. If CYP1A2 is of importance for the metabolism of MT one would expect to find an inverse correlation between the MT-AUCs and the CA clearance. However, such correlation did not exist in the current study (Rs=-0.021, NS). Since endogenous MT-AUC is dependent not only on MT elimination by CYP1A2 but also on MT secretion, it is possible that an increased MT secretion counter-balances an increased hepatic MT metabolism. If so, this could explain why the MT-AUCs and the CA clearance values were not inversely correlated in this study.

Seasonal alterations in circadian melatonin rhythms of the European wild boar and domestic gilt.

The aims of the present study were: 1) to determine if the European wild boar exhibits a circadian pattern of melatonin secretion under its natural light environment; 2) to compare this pattern with the pattern in domestic pigs reared under the light environment typical for domesticity; and 3) to determine if there are seasonal alterations in melatonin rhythms. Four to six young, pure-bred, European wild boars and four to six cross-bred (Yorkshire x Finnish Landrace) domestic gilts were sampled at 2-hr intervals for 48 hr at the spring/autumn equinoxes and summer/winter solstices. Samples were obtained via saphenous arterial catheters from the wild boars and via ear vein catheters from the domestic gilts. The ambient light intensity was recorded simultaneously with sampling both outdoors and indoors. Following ether extraction, the serum samples were assayed for melatonin using a commercial RIA (Bühlman). All the experimental animals exhibited a distinct circadian pattern in melatonin secretion, with high concentrations occurring during the scotophase. There was no difference in scotophase melatonin response between the wild boars and domestic gilts in any season in terms of mean melatonin concentration or peak value. The mean duration of increased melatonin secretion (more than two standard deviations over a mean photophase concentration) in 24 hr in the wild boars in spring, summer, autumn and winter, was 10, 6, 11 and 17 hr, respectively, and in the domestic gilts, 9, 8, 12 and 11 hr, respectively. These results demonstrate the existence of circadian rhythm in melatonin secretion in both the European wild boar and domestic pig. In both groups, the duration of secretion is subject to seasonal alterations. The results suggest no difference in photoperiodic-melatonin transduction between the European wild boar and domestic pig whether due to altered genotype or reduced light environment.

Diminished melatonin secretion in the elderly caused by insufficient environmental illumination.

The pineal hormone melatonin has some circadian regulatory effects and is assumed to have a close relation with sleep initiation and maintenance. Many previous reports have described age-related decreases in melatonin levels, especially in elderly insomniacs (EIs), which may act as causal or exacerbating factors in sleep disturbances in the elderly. Ten elderly residents with psychophysiological insomnia (mean age, 74.2 yr), 10 healthy residents of the same home [elderly control (EC) group; mean age, 72.7 yr], and 10 healthy young control subjects (mean age, 20.9 yr) living at home participated in this study. The elderly persons, especially the EIs, were exposed to significantly less environmental light and simultaneously suffered from significantly diminished nocturnal melatonin secretion. Supplementary exposure to 4 h (1000 to 1200 h, 1400 to 1600 h) of midday bright light in the EI group significantly increased melatonin secretion to levels similar to those in the young control group without circadian phase-shifting. There was a tendency for the magnitude of the increase in nocturnal melatonin secretion stimulated by bright light to parallel amelioration of sleep disturbances in these subjects. The present findings suggest that we need to pay attention to elderly individuals who suffer under conditions of poor environmental light resulting in disorganized circadian rhythms, including the sleep-wake cycle.