Effect of pinealectomy on melatonin levels in the gastrointestinal tract of birds.
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The pineal hormone melatonin controls reproduction of photoperiodic mammals and is an integral part of the circadian organization in birds. Recent findings indicate an involvement of this hormone also in more basic physiological processes, including growth, development, and aging. Melatonin may modulate growth in poultry through interaction with transcriptional factors, through interaction with hormones involved in growth control, and by modulation of energy metabolism and decreasing physical activity. Our studies showed that a single melatonin injection increased plasma growth hormone (GH) concentrations in the Japanese quail. Specific serotonin receptor blocker ketanserin did not preclude a stimulatory action of melatonin on GH synthesis. Serotonin agonist quipazine increased GH levels but failed to enhance the stimulatory effect of melatonin. Pretreatment with melatonin in drinking water did not affect the magnitude of the GH response to subcutaneous (s.c.) administration of thyrotropin releasing hormone (TRH) that considerably stimulated GH secretion. Present data suggest that melatonin modulates rather central neural pathways involved in the control of GH synthesis at the hypothalamic level than the sensitivity of the pituitary gland.
In contrast to the situation in mammals, in which circadian melatonin production by the pineal gland does not begin until some time after birth, the development of pineal gland rhythmicity is an embryonic event in the precocial domestic fowl. A distinct melatonin rhythm was found in 19-d-old chick embryos maintained under light:dark (LD) 16:8. No significant variation in melatonin levels was detected in embryos exposed to LD 8:16. The melatonin rhythm in the pineal gland and plasma of chick embryos incubated for 18 d in LD 12:12 persisted for 2 d in constant darkness indicating that melatonin production is under circadian control at least from the end of embryonic life. A 1-d exposure to a LD cycle during the first postembryonic day was sufficient to entrain the melatonin rhythm, and previous embryonic exposure to either LD or constant darkness (DD) neither modified this rapid synchronization nor did it affect the melatonin pattern during the two subsequent days in DD. It is suggested that, in contrast to the situation in mammals, the avian embryo has evolved its own early circadian melatonin-producing system because, as a consequence of its extrauterine development, it cannot use the system of its mother.
The distinct melatonin rhythm with higher concentrations during the darktime was found in plasma of both control patients and patients with colorectal carcinoma. Moderate surgery did not induce any changes in plasma melatonin levels, but a pronounced increase in both the day- and nighttime melatonin concentrations was found after surgical treatment for colon cancer. The melatonin content in the tumor tissue did not differ from that in the proximal and the distal parts of the resected gut, which were without signs of malignant changes. Neither concentrations of serotonin nor 5-hydroxyindole acetic acid differed among analyzed parts of the gut. Daytime melatonin concentrations in gut tissue (314.7 +/- 87.8 pg/g of wet tissue) were more than ten times higher than the daytime levels in circulation. It was hypothesized that increased levels of this hormone in the gastrointestinal tract may play an important protective role against the development of colorectal cancer via stimulation of the immune system, protection against free radicals, and interaction with fatty acid uptake and metabolism.
BACKGROUND: Epidemiological trials provided evidence that the cholesterol concentration in lipoproteins B, i.e. VDL, IDL and LDL, correlate significantly with the incidence of ischaemic heart disease (IHD). The objective of the present study was to assess how the fatty acid composition in plasma phosphatidyl choline affects the total and LDL cholesterol, triglyceride and apolipoprotein B concentrations in subjects with primary hyperlipoproteinaemia and dyslipidaemia. METHODS AND RESULTS: In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the concentrations of plasma lipids, lipoproteins apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. The authors provided evidence by discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and the upper quintiles (Q4 + Q5) of concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B and the independent variables were FA concentrations in plasma PC, that the total cholesterol concentration was inversely associated with the concentration of docosahexaenic acid (22:6n-3). The concentration of LDL-cholesterol correlated inversely with the concentration of palmitoleic acid (16:1n-7). Triglyceridaemia was inversely associated with the linoleic acid concentration (18:2n-6). The concentration of apolipoprotein B correlated positively with myristic acid (14:0) and negatively with concentrations of oleic acid (18:1n-9) and linoleic acid (18:2n-6). CONCLUSIONS: The submitted results indicate that the fatty acid concentrations of PC in plasma are significantly and markedly correlated with concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B. It is possible that atherogenic lipoproteins may be favourably influenced not only by the amount of fat but also by a suitable fatty acid composition.
BACKGROUND: Epidemiological trials revealed a significant inverse relationship between the cholesterol concentration in high density lipoproteins (HDL-C), apolipoprotein A-I and the incidence of ischaemic heart disease (IHD). It is assumed that the protective effects of HDL against the development of IHD are due to its important function during the reverse cholesterol transport. The HDL-C and apo A-I concentration are influenced by a number of genetic, racial, sexual, hormonal, metabolic and nutritional factors. The objective of the present investigation was to assess how the fatty acid (FA) composition in phosphatidyl choline in plasma affects the HDL-C and A-I concentration in subjects with primary hyperlipoproteinaemia and dyslipidaemia. METHODS AND RESULTS: In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the plasma concentrations of lipids, lipoproteins, apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. Using discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and upper quintiles (Q4 + Q5) of HDL-C and A-I concentrations and the independent variables FA concentrations in plasma PC, the authors provided evidence that low HDL-C concentrations are associated with 18:0 and conversely a rise of Apo-I is associated with concentrations of 18:1n-9, 18:2n-6, 18:3n-6 and 22:6n-3 in plasma phosphatidylcholine. CONCLUSIONS: The submitted results indicate that FA concentrations in plasma PC are significantly and markedly associated with HDL-C and A-I concentrations in subjects with hyperlipoproteinaemia and dyslipidaemia. This opens the opportunity to influence favourably the concentration of these parameters by changing the dietary fatty acid composition.
The pineal cells of chick embryos incubated in vitro exhibited a daily rhythm of melatonin synthesis under a 12:12 light:dark (LD) cycle at the embryonic days 16 and 19. In order to elucidate whether cyclic adenosine monophosphate (cAMP)--a component of the melatonin generating system--is already at work in the embryonic period, we measured the effects of forskolin and isobuthylmethylxantine (IBMX) on melatonin production, cAMP efflux and accumulation. Forskolin (after 10, 20, 30, 45, 60 and 90 min of administration) and IBMX (6 h), when applied during the light phase of LD cycle, stimulated melatonin production and cAMP efflux and accumulation during the embryonic period (at days 16 and 19 fo development). Our results suggest that the biochemical pathway involving cAMP, which controls melatonin production in the postnatal period, is developed before hatching and already on embryonic day 19 works in a way similar to that in post-hatched chicks. Differences in response to cAMP stimulation between 16- and 19-day-old pinealocytes seem to be mostly quantitative.
Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).
Melatonin as a highly lipophilic compound readily enters all subcellular compartments and acts by various mechanisms. In the present study, we investigated the effects of different concentrations of melatonin in medium (physiological and supraphysiological doses) at two treatment times (48 and 120 hr) on growth and changes of growth parameters of cultured chick embryonic skeletal muscle cells. The physiological doses of melatonin (100 pg to 10 ng/ml of medium) stimulated proliferation of cells and raised DNA, RNA protein contents and an incorporation of [3H]leucine into cell protein after 48 hr of treatment. The prolongation of exposure to melatonin in the physiological dose to 120 hr or an increase of melatonin dose to a supraphysiological one evoked the inhibition of cell growth and proliferation by decreasing the number of cells and the amount of labeled leucine incorporated into cell protein. Results demonstrate that melatonin's action in these cells is time and dose dependent.
In young European starlings, as in other avian species, high-amplitude 24-hr rhythms in plasma and pineal melatonin are already present around the time of hatching. In chickens this rhythmicity results at least partly from the light sensitivity of the melatonin-producing and -secreting system. In contrast to the chicken, the starling is a hole-nesting bird, and it seemed questionable whether the low light intensities in the nest are sufficient to synchronize perinatal melatonin rhythms. We therefore exposed starling eggs to light cycles roughly simulating those measured in nest-boxes, i.e., an 11-hr phase of complete darkness and a 13-hr phase consisting of 15 min of dim light (10 lux) alternating with 30 min of darkness. For one group the photophase lasted from 0600 to 1900 hr; for the other group the photophase lasted from 1800 to 0700 hr. In approximately 10-hr-old hatchlings of both groups, plasma and pineal melatonin concentrations were high during the dark phase and low during the light phase. We conclude that perinatal low-amplitude light intensity changes of the kind experienced by hatching starlings in the field are sufficient for synchronizing the melatonin-producing and -secreting system in the pineal and possibly other organs.
BACKGROUND: Some epidemiological, clinical and experimental studies have shown that intake of n-3 fatty acids (FA) lowers the incidence of coronary heart disease (CHD). The effects of fish oil and n-3 FA on the development of atherosclerosis include several factors such as the platelet-vascular wall interaction, modulation of eicosanoid metabolism as well as platelet aggregation and its survival time. There were also changes in the fibrinolytic system and cardiovascular reactivity observed. Effects of n-3 FA on lipid and lipoprotein metabolism exert antiatheromatous action as well. The aim of the study was to evaluate changes in plasma lipid risk factors for CHD in subjects with primary hyperlipoproteinemia (HLP) after the administration of fish oil rich in n-3 FA. METHODS AND RESULTS: A total of 82 patients (61 men and 21 women) were administered fish oil (3.5 g n-3 FA daily) for a period of 3 weeks. The group of hyperlipidemics included 9 patients with HLP IIA, 29 with HLP IIB, and 35 with HLP IV. Seven patients had HLP type V while two had HLP type III. Intake of fish oil led to a mild decrease in total plasma cholesterol which was significant in the whole group and in HLP type V. Triglyceride levels declined significantly in all HLP phenotypes, with the changes being most marked in HLP types IIB, IV, and V. We also observed a significant increase in cholesterol concentration in HDL and in the both HDL2 and HDL3 subfractions in the whole group and all HLP phenotypes as well. On the other hand no statistical significant changes were observed in LDL-cholesterol levels. The levels of apo B rose significantly only in HLP type V. A statistically significant increase was found in apo A-1 levels in the whole group and in the HLP IIB subgroup. Fish oil administration led to a mild reduction in diastolic pressure and uricemia. In part of patients fish oil induced decrease in lipoprotein(a) concentration was observed.
BACKGROUND: The authors discuss the effect of administration of fish oils rich in n-3 fatty acids in diabetic patients type 2 and draw attention to the possible deterioration of glucose homeostasis. The objective of the investigation was to assess changes of the lipid and carbohydrate metabolism in type 2 diabetics with associated dyslipidaemia after enrichment of the diet with n-3 fatty acids. METHODS AND RESULTS: To 17 patients with type 2 diabetes and dyslipidaemia fish oil containing 5.5 g n-3 fatty acids per day was administered. After six weeks a decline of triglycerides was recorded (-47%, P < 0.01), free fatty acids (-27%, P < 0.01) and a rise of HDL2-cholesterol (25%, P < 0.05). The concentration of apo B, apo A-1, LDL- and HDL cholesterol did not change significantly. There were no significant changes of the blood sugar level, glycosylated haemoglobin and fructosamine. The insulin and C-peptide concentration on fasting (and after glucagon stimulation) did not change significantly. With regard to the HDL2-cholesterol and 18:0 fatty acid concentration in serum the group can be divided into responders (with a decline of glycosylated haemoglobin) and non-responders. The two groups have a reverse trend of blood sugar levels and insulinaemia and differ as to the metabolism of 18:1 n-7 acid. CONCLUSIONS: Enrichment of the diet with n-3 fatty acids in diabetics with dyslipidaemia has a favourable effect on the plasma lipid spectrum without causing deterioration of parameters of diabetes compensation. Among the group of patients some can be found where fish oil administration improves also glucose homeostasis.
Plasma concentrations of thyroid hormones (TH) and growth hormone (GH) during postnatal development in the precocial Japanese quail (Coturnix japonica), and the altricial European starling (Sturnus vulgaris) were measured. Developmental changes in plasma TH found in the starling, differ considerably from those detected in quail. In quail rather high triiodothyronine (T3) values were measured during the first few days after hatching. Subsequently a steady decrease of plasma T3, to adult levels, was observed. Thyroxine (T4) concentrations did not change significantly during the period studied. In starlings, on day 1, plasma T3 was low and T4 was at or below the assay detection limit. An increase in concentrations of both hormones occurred between day 1 and day 5 after hatching. A gradual increase of T4 occurred afterwards, while plasma T3 levels remained nearly constant during this growing period. Plasma GH concentrations showed a similar pattern in both species. There was an increase during first days after hatching and GH concentrations peaked at day 7 in quail and day 5 in starlings. A subsequent decrease was observed in both species. Although the GH profiles in species studied were comparable, there were noticeable differences in their growth rates. Thus different developmental strategies have been reflected in different developmental patterns of TH in precocial Japanese quail and altricial European starling whereas developmental changes of GH levels were similar in both species.
Osmotic minipumps containing either saline or recombinant human insulin-like growth factor-II (IGF-II) were implanted into 4-wk-old female broiler chickens such that the treated chickens received 0.5 mg IGF-II/kg body weight per d. At the end of the trial, no differences in body weight gain or bone length were detected between the treated and control groups. Similarly, there were no differences between the two treatments with respect to heart, spleen, liver, or bursa of Fabricius weight. The relative weight of the abdominal fat pads was greater (P < 0.05) in the birds treated with IGF-II than in the controls, whereas the weight of breast muscle was reduced (P = 0.06) in the birds treated with IGF-II. There was no effect of IGF-II treatment on feed intake or feed conversion efficiency. Plasma growth hormone (GH) levels were acutely depressed by 15 min after IGF-II administration; and also after 2 wk of IGF-II treatment. Plasma triiodothyronine (T3) concentrations were significantly depressed by IGF-II treatment. These results suggest that IGF-II may not stimulate growth in chickens, but can act as a nutrient partitioning agent, either directly or indirectly through altering plasma GH or T3 concentrations.
The chick pineal gland exhibits circadian rhythms in melatonin synthesis under in vivo and in vitro conditions. A daily rhythm of melatonin production was first detectable in pineal glands isolated from chick embryos at embryonic day 16 and incubated under a LD cycle. All pineal glands isolated from 17-day-old and older embryos were rhythmic while no gland isolated at embryonic day 14 and 15 exhibited a daily rhythm in melatonin synthesis. Melatonin production in static cultures of embryonic pineal cells was rhythmic over 48 h if the cells were kept under a LD cycle. When embryonic pineal cells were incubated in constant darkness the rhythm in melatonin production was damped within 48 h. These results suggest that chick pineal cells from embryonic day 16 onwards are photosensitive but that the endogenous component of the melatonin rhythm is not completely developed at that age. A soluble analogue of cAMP stimulated and norepinephrine inhibited melatonin synthesis in cultured embryonic pineal cells. These findings indicate that the stimulatory and inhibitory pathways controlling melatonin synthesis in the mature pineal gland are effective in pineal cells isolated from chick embryos at least 2 days before hatching.
BACKGROUND: In some patients with ischaemic heart disease disorders of the lipoprotein metabolism were found although the plasma cholesterol and triglyceride levels were not elevated. The objective of the present work was to assess parameters of the lipoprotein metabolism which could differentiate normolipidaemic probands with an increased risk of myocardial infarction. METHODS AND RESULTS: The authors examined a group of 21 men with normal values of plasma cholesterol and triglycerides who had suffered 6 months to 3 years ago from a myocardial infarction. As compared with a control group of normolipidaemic men without evidence of ischaemic heart disease, these patients had significantly lower HDL-C concentrations (-22%, p < 0.01), in particular due to a lower sub-fraction HDL,-C (-29%, p < 0.001), a higher apolipoprotein B concentration in LDL (+36%, p < 0.00) and a lower value of the cholesterol/apolipoprotein B ratio in LDL (-25%, p < 0.05). The total cholesterol, triglyceride, LDL cholesterol, HDL2-cholesterol, apolipoprotein A-1 concentration and cholesterol/apolipoprotein A-1 ratio in HDL did not different significantly. The method of discrimination analysis revealed that for the differentiation of the two groups assessment of apolipoprotein B in LDL and HDL3-C are most useful. By this approach 80% of the patients in the group were correctly classified. CONCLUSIONS: The results of the presented work confirmed the importance of assessment of apolipoprotein B and HDL-C, incl. its sub-fractions for estimating the risk of ischaemic heart disease in normolipidaemic subjects.
To investigate the effects of reproduction and associated stimuli on the circannual cycles of African stonechats Saxicola torquata axillaris birds were held for 29 months in aviaries under a constant equatorial (12.25 h) photoperiod, either singly (10 females and 10 males) or in 10 male/female pairs. The birds of all 3 groups went through circannual cycles in gonadal size, plasma LH and molt, but groups differed with regard to actual reproductive performance. During the second cycle, only one of the singly-held females laid eggs and incubated. In contrast, in the paired females egg-laying and incubation occurred in all but one bird. About 50% of the clutches from paired females contained fertilized eggs confirming the expectation of behavioral differences between the paired and unpaired birds. However, despite differences in reproductive performance there were no differences in either circannual period or duration of reproductive phases. Moreover, there was no correlation between number of broods produced per season and circannual parameters of the paired females. Therefore, the temporal course and, particularly, the period during which reproduction is possible is rigidly determined by an endogenous program that is not influenced by reproductive performance. A rigid program of this kind may be advantageous in the tropics because it prevents prolongation of the breeding season in years with favourable conditions which in turn could jeopardize optimal timing of breeding in the following year and thus reduce lifetime reproductive success.
The effects of passive immunization against IGF-1 either alone, or together with immunization against IGF-2, on growth and metabolism were examined in chickens. Immunization against IGF-1 alone had no effect upon any aspect of growth, carcass composition, efficiency of energy utilization or hormone concentrations studied. Immunization against both IGF-1 and IGF-2 together resulted in a lighter final body weight (P < 0.05) compared with controls. Immunization against both IGFs together decreased abdominal fat content (P < 0.05) and resulted in a heavier mean spleen weight (P < 0.01). The joint immunization was also associated with elevated plasma T3 concentrations. These data may indicate a role for IGF-2, but not for IGF-1, in fat metabolism in chickens.