Showing papers in "Journal of Pineal Research in 1989"
TL;DR: It is suggested that when examining the melatonin sensitivity of patient groups to artificial light, an appropriate light intensity should be established in each laboratory, and light of less intensity may be more suitable to dichotomize patient groups from control subjects.
Abstract: Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200-350 lx) may be more suitable to dichotomize patient groups from control subjects.
404 citations
TL;DR: The results have indicated that only five inbred strains have pineal melatonin content, with higher levels during the night and lower levels in the day; the other 31 strains do not contain detectable melatonin in their pineal gland at any of times examined.
Abstract: Pineal melatonin content at several times during the day and night was measured in 36 inbred strains of mice (Mus musculus) kept under LD 12:12 cycles. The results have indicated that only five inbred strains have pineal melatonin content, with higher levels during the night and lower levels during the day; the other 31 strains do not contain detectable melatonin in their pineal gland at any of times examined. The former group includes two commonly used strains (C3H/He and CBA/Ms) and three wild-derived strains (Mol-A, Mol-Nis, MOM). C3H and CBA mice showed a similar pattern of pineal melatonin rhythm with a peak at 2 hours before lights on. The peak levels were about 150 pg/gland in both strains. The rhythmic patterns of melatonin content in Mol-A, Mol-Nis, and MOM were slightly different from those in CBA and C3H. In the wild-derived strains, the peak of melatonin content did not occur at 2 hours before lights on but tended to occur at midnight. The peak levels were 67-91 pg/gland at the highest point in these strains.
273 citations
TL;DR: Surprisingly, M injected into intact mice decreased FTT to levels comparable to those observed in 5‐HT implanted, M‐treated mice, and may indicate that part of M action on the gut movement is mediated by extraintestinal mechanisms.
Abstract: In vitro melatonin (M) reduced the tone of gut muscles and counteracted the tonic effect of serotonin (5-HT). In vivo 0.1 to 4 mg of 5-HT (contained in beeswax implants) decreased the food transit time (FTT) in a dose-dependent manner, but higher doses (5 and 6 mg) increased the FTT. Melatonin injected intraperitoneally into mice bearing 5-HT implants (2 mg per animal) blocked partly the serotonin effect and increased FTT by 50%; however, no dose-dependent effect was observed when doses between 0.01 and 1 mg were used. Surprisingly, M injected into intact mice decreased FTT to levels comparable to those observed in 5-HT implanted, M-treated mice. Again, this significant decrease was not dose-dependent between 0.02 and 1 mg. Although in vitro the maximal inhibition of serotonin-induced spasm was achieved when the M: 5-HT ratio was 50–100: 1, in vivo the effective ratio was about 1: 1. This may indicate that part of M action on the gut movement is mediated by extraintestinal mechanisms. A hypothetical, counterbalancing system of M and 5-HT regulation of gut activity (similar to adrenaline-acetylcholine system) is proposed.
73 citations
TL;DR: The findings indicate that the GMBF and gastric injury are related; the reduction in GMBF, however, may not be the sole factor responsible for ulceration, and suggest that melatonin may act as a modulator for 5‐HT action on the gastrointestinal tract.
Abstract: Effects of melatonin and serotonin on ethanol ulceration and mucosal blood flow in the rat stomach were investigated. Melatonin and serotonin (5-HT) administration did not produce observable gastric injury in the ex vivo stomach, but the 5-HT dose dependently reduced glandular mucosal blood flow (GMBF) in this organ. Ethanol depressed GMBF and induced visible glandular mucosal injury. The latter effect was prevented by melatonin preincubation. Serotonin pretreatment aggravated the gastric mucosal injury and GMBF changes induced by ethanol; these actions were partially reversed by melatonin. The findings indicate that the GMBF and gastric injury are related; the reduction in FMBF, however, may not be the sole factor responsible for ulceration. The antagonistic effects of melatonin on 5-HT action on the stomach suggest that melatonin may act as a modulator for 5-HT action on the gastrointestinal tract.
65 citations
TL;DR: In this paper, the localization in the superior cervical ganglia (SCG) of neuropeptide Y-containing neurons innervating the pineal gland was investigated by using fluorescent tracer Fluoro-Gold (FG).
Abstract: The aim of this study was to investigate the localization in the superior cervical ganglia (SCG) of neuropeptide Y-containing neurons innervating the pineal gland. Following injection of the fluorescent tracer Fluoro-Gold (FG) into the superficial part of the pineal gland and retrograde axonal transport, labeled cells were observed predominantly in the rostral third to half of SCG sections (average number 239 per ganglion). Incubation of the sections with neuropeptide Y (NPY) antiserum showed that the vast majority of neurons exhibit NPY-like immunoreactivity (NPY-LI). The comparison of cells labeled with FG and those containing NPY revealed that nearly three fourths of retrogradely labeled neurons also exhibit NPY-LI. Incubation of pineal gland sections with NPY antiserum showed immunoreactive axons, relatively sparse and scattered throughout the superficial part of the organ and the pineal stalk. The present results confirm the assumption that, in rodents, pineal NPY originates from the superior cervical ganglia.
59 citations
TL;DR: It is suggested that the pineal gland may modulate the circulating levels and liver receptor concentrations of insulin and glucagon in rats and induce a down‐regulation of liver receptors in Pn rats.
Abstract: The studies described here were undertaken to characterize the hepatic insulin and glucagon receptors of control (C), pinealectomized (Pn), and melatonin-treated pinealectomized (Pn + Mel) rats. Compared with C rats, an increase in plasma glucose and glucagon levels and a reduction in circulating concentrations of insulin in Pn animals were observed. Melatonin treatment of Pn rats reverses all three parameters toward the normal values. In liver membranes, insulin binding was lower in Pn than in C rats, and glucagon binding was greater in Pn than in C animals; in Pn + Mel rats both insulin and glucagon binding reverse toward the normal values that were observed in C rats. The modifications in hormone binding reflect changes in the number of receptors but not in the affinity constants. The time courses of hormone association and dissociation from liver membranes were similar in all three experimental groups. The degradation of both hormones by liver membranes was similar in all three groups. Insulin receptor degradation also was similar in the three groups, while glucagon receptor degradation was similar in the liver membranes of C and Pn rats but smaller in Pn + Mel animals. These findings suggest that the pineal gland may modulate the circulating levels and liver receptor concentrations of insulin and glucagon. In addition, our results indicate that insulin and glucagon did not induce a down-regulation of liver receptors in Pn rats.
51 citations
TL;DR: The results show that nocturnal blood melatonin levels may be suppressed by the acute administration of a GABAergic agent, suggesting that GABA may be involved in the modulation of pineal activity in man.
Abstract: Several studies suggest that GABAergic mechanisms may be involved in the modulation of melatonin secretion. However, conflicting results have been reported in animal studies; in humans the issue has not been widely investigated. In the present study, using a double-blind design, six healthy men received orally, at midnight, 10 mg of diazepam, a GABAergic agent, or placebo, on two different occasions 1 week apart. Blood samples were collected, in the dark, immediately before the drug administration, and at 12:30, 1, 2, 3, and 4 AM. Serum melatonin was measured by a radioimmunological method with [125I]melatonin as a tracer. Two-way ANOVA with repeated measurements disclosed a significant effect for treatment (P less than 0.01), for time (P less than 0.0004), and for treatment X time interaction (P less than 0.05). Following diazepam administration, serum melatonin levels observed at 2, 3, and 4 AM were significantly lower than the corresponding values following placebo (P less than 0.002 at 2 and 4 AM; P less than 0.03 at 3 AM [Students' paired t test]). These results show that nocturnal blood melatonin levels may be suppressed by the acute administration of a GABAergic agent, suggesting that GABA may be involved in the modulation of pineal activity in man.
51 citations
TL;DR: A direct suppressive effect of Mel (but not of NAc‐5HT) on NK activity of human peripheral blood lymphocytes can be assumed.
Abstract: One of the important immune functions influenced by neuroendocrine factors is natural killer (NK) activity, which is directed against neoplastic and virus-infected cells. The effects of melatonin (Mel) and N-acetylserotonin (NAc-5HT) on NK activity of human peripheral blood lymphocytes were investigated. Leukocytes of healthy human subjects were used in the experiment. NK activity was estimated by measurement of radioactive chromium (51Cr) release from human leukemia cells K 562 (target cells). The previous exposure of human lymphocytes (effector cells) to Mel in concentrations of 10(-6) M and 10(-10) M resulted in an inhibition of NK activity (P less than 0.01) for all the examined effector-target cell ratios (10:1; 20:1, 40:1). NK activity was also suppressed by Mel (10(-8) M), but only if effector-target ratio equal to 20:1 was used (P less than 0.02), and by Mel (10(-12) M) for effector-target ratio equal to 40:1 (P less than 0.05). In none of the examined concentrations did NAc-5HT inhibit NK activity of human lymphocytes. On the basis of the data reported above, a direct suppressive effect of Mel (but not of NAc-5HT) on NK activity of human peripheral blood lymphocytes can be assumed.
49 citations
TL;DR: The perifusion system was found useful in order to follow the characteristics of melatonin release from pineal glands and should allow investigations of neuronal or hormonal control of pineal gland activities.
Abstract: In previous studies, noradrenaline was found to elicit a rise of melatonin secretion through activation of typical beta-adrenergic receptors. In the present study, a perifusion system was developed to characterize the kinetics of melatonin release from rat pineal glands. Isolated pineal glands from adult male rats were continuously perifused for 15 h in a Krebs-Ringer solution, and the concentration of melatonin in the effluent perifusate was monitored using a specific radioimmunoassay. The rate of release of melatonin declined during the first 3-4 h of perifusion and then remained fairly stable for at least 11 h. The spontaneous release of melatonin was around 20 pg per min and per gland. When pineal glands were stimulated with isoproterenol, melatonin release output linearly increased for at least 2 h after the stimulation. The increase in melatonin release depended on the isoproterenol concentration and on the duration of the stimulation. The analysis of the pattern of melatonin secretion by a single rat pineal gland showed that the secretion was irregular but did not present a clear feature of pulsatile or oscillatory release over a 11 h-long study. The perifusion system was found useful in order to follow the characteristics of melatonin release from pineal glands and should allow investigations of neuronal or hormonal control of pineal gland activities.
44 citations
TL;DR: Night interruption by 1 h lighting resulted in an abrupt decline of CSF melatonin to the basal level within 30 min and immediate recovery to the previous high level after reestablishment of the dark phase.
Abstract: Melatonin profiles in the cerebrospinal fluid (CSF) of conscious goats were examined under long-day (16L:8D) and short-day (8L:16D) environments. CSF melatonin, collected from the lateral ventricle, showed distinct 24 h rhythms with high concentrations being restricted to the dark phase, which averaged 1,320.6 pg/ml under 16L:8D and 660.6 pg/ml under 8L:16D. On the contrary, the nocturnal rise in CSF melatonin was totally absent in the pineal sympathetically denervated animals. Night interruption by 1 h lighting (about 400 lux at the height of goat's head) resulted in an abrupt decline of CSF melatonin to the basal level within 30 min and immediate recovery to the previous high level after reestablishment of the dark phase. The CSF/plasma ratio was 10.8-18.4 during the dark phase and 1.7-1.8 during the light phase. CSF and plasma melatonin levels were also examined after exogenous melatonin given either peripherally or intraventricularly. Continuous subcutaneous infusion of melatonin (5 micrograms/h) maintained melatonin levels in the plasma about 3 times higher than that in the CSF during its application. On the other hand, an intraventricular injection of 2 micrograms melatonin elevated plasma melatonin by 100 pg/ml within 1 min. These results indicate that turnover of CSF melatonin is fairly rapid and favor a hypothesis for direct access of pineal melatonin to the brain ventricular system in the goat.
43 citations
TL;DR: The results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin, and development of a human model of Pineal responsiveness to exercise may contribute to the elucidation of exercise‐associated reproductive disorders.
Abstract: Previous human studies have indicated that daytime melatonin levels increase when the organism is subjected to the stress of fasting and exercise. Melatonin, epinephrine, and norepinephrine levels were measured during a mock run and in the course of treadmill exercise performed before (T-1), during (T-2), and following (T-3) a progressive conditioning (running) program. Hormonal responses to the training program were determined by comparing values at T-1 and T-3. Plasma melatonin, epinephrine, and norepinephrine levels rose significantly (P less than .01) from baseline values for each exercise intensity during all three treadmill runs. While a dose-response trend was observed in each of the norepinephrine and epinephrine trials, there appeared to be a progressive diminution of this relationship in melatonin between intensities. Further, as training progressed, the peak melatonin concentration was decreased by 52% from T-1 to T-3, while peak epinephrine and norepinephrine values diminished only 19% and 8%, respectively. These results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin. Development of a human model of pineal responsiveness to exercise may contribute to the elucidation of exercise-associated reproductive disorders.
TL;DR: The cerebrospinal fluid of the cisterna magna and the lateral ventricle had temporal patterns of melatonin that were similar to those found in jugular plasma, and this medium is an important route of transport for melatonin from the pineal gland to putative target tissues.
Abstract: In this study we examined the cerebrospinal fluid (CSF) for regional differences in the concentration of melatonin. Cerebrospinal fluid samples were collected at hourly intervals from either the lateral ventricle or the cisterna magna of nine Merino ewes and were compared against jugular plasma. The study revealed that the CSF of the cisterna magna and the lateral ventricle had temporal patterns of melatonin that were similar to those found in jugular plasma. However, the concentrations of melatonin within the CSF obtained from the lateral ventricle were one order of magnitude higher than those of the jugular plasma, as verified by gas chromatography and mass spectrometry, while the melatonin concentrations within the CSF obtained from the cisterna magna were comparable to those of the jugular plasma. The data from this study suggest that there may be regional differences in the concentration of melatonin within the CSF and indicate that this medium is an important route of transport for melatonin from the pineal gland to putative target tissues.
TL;DR: Melatonin, in all the examined doses, significantly decreased mean mitotic activity rate (MMAR) of the adrenal cortex in both male and female mice.
Abstract: The goal of this study was to examine the effects of melatonin, as well as those of melatonin and corticotropin (1-24 adrenocorticotrophic hormone (ACTH); Synacthen Depot) administered together, on the mitotic activity of adrenocortical cells in male and female mice. Melatonin was given subcutaneously once daily, in late-afternoon injections (between 16:00 and 18:00) in doses of 1 microgram, 10 micrograms, and 100 micrograms, and ACTH in a dose of 0.1 mg (10 U) daily for 10 days. Additionally, the highest dose of melatonin (100 micrograms daily) was administered together with ACTH. The metaphase-arrest technique using colchicine as a stathmokinetic agent was employed in the study. Melatonin, in all the examined doses, significantly decreased mean mitotic activity rate (MMAR) of the adrenal cortex in both male and female mice. Moreover, in a dose of 100 micrograms, melatonin suppressed the mitogenic effect of ACTH on the adrenal cortex. Furthermore, the present study investigated the effects of melatonin (5 x 10(-7)M), N-acetylserotonin (NAc-5HT) (5 x 10(-7)M), and ACTH (250 mU/ml or 1,000 mU/ml) alone as well as the effect of ACTH (250 mU/ml) applied jointly with melatonin on the mitotic activity of adrenocortical cells in rat adrenal explants incubated in vitro. Both pineal indoleamines (melatonin and NAc-5HT) significantly decreased the MMARs of adrenocortical cells. Corticotropin, as well as ACTH and melatonin applied together, also reduced the MMAR of adrenocortical cells. The present data suggest that melatonin may be directly involved in the inhibitory control of adrenocortical cell proliferation.
TL;DR: Findings indicate that in either pinealectomized‐diabetic or diabetic rats there were significant changes in the circulating and liver insulin and glucagon receptor concentrations and that the changes inThe circulating levels of both pancreatic hormones were more pronounced in pinealctomized-diabetic animals.
Abstract: The studies described in this paper were undertaken to characterize the circulating and hepatic insulin and glucagon receptor concentrations of control (C), diabetic (Db), and pinealectomized-diabetic (Pn + Db) rats. Compared with C rats, an increase in plasma glucose and glucagon levels and a reduction in circulating insulin concentrations in Db animals was observed; these differences were greater in Pn + Db rats. In liver membranes, insulin binding was lower in Db and in Pn + Db than in C rats, and glucagon binding was greater in Db and in Pn + Db than in C rats. The modifications in hormone binding did not reflect changes in the affinity constants. The time courses of hormone association and dissociation from liver membranes were similar in all three experimental groups. The degradation of both hormones and their receptors was similar in all three groups. These findings indicate that in either pinealectomized-diabetic or diabetic rats there were significant changes in the circulating and liver insulin and glucagon receptor concentrations and that the changes in the circulating levels of both pancreatic hormones were more pronounced in pinealectomized-diabetic animals. In addition, the absence in Db and in Pn + Db rats of the insulin and glucagon down-regulation of their own receptors could further modify metabolic activities in these animals.
TL;DR: The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.
Abstract: In a double-blind study, melatonin (50 mg) or placebo was administered daily to 25 subjects at 9 am or 7 pm for 1 week. Self-rated fatigue as evaluated by the Stanford Sleepiness Scale (SSS) was significantly increased during the 3 hours following melatonin intake in the morning, whereas, after administration in the evening, no difference between melatonin and placebo could be distinguished. Sleep onset latency slightly decreased in both melatonin groups without reaching statistical significance. No cumulative effects on sleep or behavior were observed. Twelve pituitary and peripheral hormones measured under baseline and partly (in the evening groups) under stimulated conditions before and after the trial did not change. The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.
TL;DR: MTN and MTOL appeared to be more potent than MEL in inducing the aforementioned changes, whereas MIAA failed to exert similar effects.
Abstract: The effects of late-afternoon injections of melatonin (MEL), 5-methoxytryptamine (MTN), 5-methoxytryptophol (MTOL), and 5-methoxyindole-3-acetic acid (MIAA) on testicular and seminal vesicular histology in the golden hamster were examined. MEL, MTN, and MTOL injections caused a reduction in the diameters of seminiferous tubules and an inhibition of spermatogenesis. Testicular regression ranged from a decrease in the abundance of late spermatids and mature spermatozoa in some animals to an almost complete loss of spermatogenesis in others. Sertoli cells were more resistant to the treatment than other cellular components of the seminiferous tubules. Leydig cells were reduced in size, showed a great reduction in cytoplasm, and possessed shrunken and angular nuclei. The epithelial cells of seminal vesicles were reduced in size and became cuboidal or low columnar. Some secretory cells possessed pyknotic nuclei and had minimal secretory activity. MTN and MTOL appeared to be more potent than MEL in inducing the aforementioned changes, whereas MIAA failed to exert similar effects.
TL;DR: It is concluded that extra retinal and extra pineal photoreceptors also are involved in influencing seasonal reproduction and the role of the pineal in catfish reproduction is variable and depends upon the photoperiod to which they are exposed as well as on the time of the year and the stage of the reproductive cycle.
Abstract: To investigate the relative importance of pineal, and eyes, and melatonin treatment on ovarian activity, catfish. Heteropneustes fossilis subjected to pinealectomy, eye enucleation, or both were exposed to short (LD 9:15) or long (LD 14:10) photoperiod during the different stages of the annual reproductive cycle. During the preparatory period, pinealectomy accelerated ovarian recrudescence under long photoperiod, but no effects of pinealectomy were observed under short photoperiod. Pineal has no influence on ovarian activity during the prespawning and spawning periods of the reproductive cycle. In the late postspawning period, ovarian recrudescence is accelerated after pinealectomy in catfish maintained under short photoperiod (LD 9:15 at 25 degrees C). But under long photoperiod (LD 14:10 at 25 degrees C), pinealectomy delayed ovarian recrudescence. An investigation into the role of the eyes revealed that eye enucleation nullifies the inhibitory effects of LD 9:15 and represses the stimulatory effects of LD 14:10. Combined surgery inhibited ovarian development under both the regimes. It is significant that pinealectomy and/or blinding neither counteracted nor delayed the postspawning ovarian regression. The findings suggest that the role of the pineal in catfish reproduction is variable and depends upon the photoperiod to which they are exposed as well as on the time of the year and the stage of the reproductive cycle. It is concluded that extraretinal and extrapineal photoreceptors also are involved in influencing seasonal reproduction. Further, no effects of melatonin treatment on ovarian activity or on vitellogenin levels during the preparatory or prespawning periods were observed, indicating that the pineal effects on gonadal activity in catfish may not be mediated through the secretion of melatonin.
TL;DR: In female European hamsters killed in spring and early summer, pineal melatonin content exhibited no day/night rhythm, which might mean that in the European hamster it is not melatonin but another substance that is of importance in photoperiodism.
Abstract: In female European hamsters killed in spring and early summer, pineal melatonin content exhibited no day/night rhythm. Absolute levels measured were relatively low, being on the order of daytime levels detected in other hamster species. An absence of day/night changes in the activity of N-acetyltransferase was also observed. However, a marked rhythm in pineal serotonin (5-HT) was found, an abrupt large increase being observed at the beginning of the light period. The day /night rhythm of pineal 5-HIAA content is similar to that of 5-HT. This absence of rhythm in pineal melatonin formation might mean that in the European hamster it is not melatonin but another substance that is of importance in photoperiodism. An absence of melatonin rhythm, however, could also be simply a peculiar pattern of melatonin production observed at a given period of the year. In this case, melatonin would be able to transduce photoperiodic information in the European hamster, as in other photope riodic species.
TL;DR: The results of these studies are interpreted to indicate that for the synthesis of melatonin, the pineal D2‐dopaminergic receptors may function independently from those of the betai‐adrenergic receptor sites.
Abstract: In a previous study, we identified in the bovine pineal gland two [3H]spiroperidol-binding sites with KD values of 0.18 and 2.1 nM and Bmax values of 37 and 630 fmol/mg protein, respectively. In this study, the status of dopamine in the bovine pineal glands was delineated further by measuring the relative concentrations of dopamine and norepinephrine and the relative concentrations of serotonin and melatonin. Furthermore, the presence of 4.0 +/- 0.6 micrograms/dopamine/gm tissue encouraged us to delineate the effects of select dopaminergic receptor agonists and antagonists on the synthesis of melatonin in vivo and on the activity of N-acetyltransferase in the rat pineal gland in culture. The acute administration of haloperidol (3 mg/kg intraperitoneally [ip]) or sulpiride (200 mg/kg ip) increased the concentration of melatonin in the pineal gland from 160.6 +/- 8.18 to 327.6 +/- 45.43 and 306.5 +/- 40.53 pg/gland, respectively. Dopamine exhibited dual effects on the activity of N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM, and the later effect was blocked by propranolol. D2-dopaminergic receptor agonists such as bromocriptine (4.0 microM) or LY-171555 (10.0 microM) partially attenuated the norepinephrine-induced stimulation of N-acetyltransferase, and these attenuating effects were reversed by D2-dopaminergic antagonists such as haloperidol (10 microM) or domperidone (10 microM). The results of these studies are interpreted to indicate that for the synthesis of melatonin, the pineal D2-dopaminergic receptors may function independently from those of the beta 1-adrenergic receptor sites. Furthermore, the said D2-dopaminergic receptor are amenable to down regulation since the activity of N-acetyltransferase remained unaltered (0.0717 vs. 0.0729 nmol/gland/h) following chronic treatment (4 mg/kg ip/day for 30 days) with bromocriptine.
TL;DR: Comparison of the effectiveness of short day and melatonin injections in juvenile and adult voles suggests that while short days inhibited testicular development of young animals more than it induced regression of adults, this decrease in responsiveness may involve factors other than alterations in the nocturnal pattern of melatonin production.
Abstract: We tested whether juvenile males of Microtus pennsylvanicus were more sensitive than adults to the suppressive effects of short photoperiods. Voles were transferred to short photoperiods (10L:14D) at 20 or 80 d of age, and 60 d later (i.e. at 80 or 140 d) the animals were killed at intervals throughout the day and night. Pineal glands were collected for measurement of melatonin, and the testes were weighed. There were no differences in paired testicular weights of 80 and 140 d old animals held on long days (median testicular weights: 1,953 and 1,843 mg). In contrast, median testicular weights of voles held on short days were 504 and 1,112 mg, respectively, at 80 and 140 d of age; the testicular weights of both groups were significantly different from their age-matched controls (P less than .001, two-sample t-tests on log transformed data). The responses of the two age groups were compared by normalizing the individual values by the mean and variance of the respective long-day controls. This comparison suggests that the responsiveness to photoperiod decreases as the animals age (t-test, P = .01). Duration and amplitude of the nocturnal rise in pineal melatonin content were similar in differently aged animals. In two experiments, voles were injected daily with melatonin from 20 to 80 or 80 to 140 d of age. Melatonin-injected animals had smaller testes than did saline-injected controls (ANOVA: P = .01), and injections were more effective in the afternoon than in the morning (P = .01). Comparison of the effectiveness of short day and melatonin injections in juvenile and adult voles suggests that while short days inhibited testicular development of young animals more than it induced regression of adults, this decrease in responsiveness may involve factors other than alterations in the nocturnal pattern of melatonin production.
TL;DR: A linear inverse correlation between the circadian mesor of plasma melatonin and the basal and LH‐RH stimulated LH levels was found, suggesting the persistence of a certain melatonin secretion during the light hours in both anorectic and obese patients could play an inhibitory role on the pituitary‐gonadal function in these subjects.
Abstract: In order to study the possible relationships between melatonin secretion and pituitary-gonadal function, the circadian rhythm of plasma melatonin, the basal levels of estradiol-17beta and testosterone and the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH) stimulation were evaluated in normally cycling healthy women and in two groups of women with menstrual dysfunctions related to eating disorders (19 patients with anorexia nervosa and 16 with primary obesity). The circadian rhythm of plasma melatonin reached statistical significance in anorectic patients but not in obese patients. The mean 24 h melatonin level was significantly higher in anorectic than in obese patients and in control subjects. However, both groups of patients shared some abnormalities of melatonin circadian pattern, such as increased ratio between day and night melatonin levels, abnormal secretory peaks during the light hours and great interindividual variability for timing, amplitude, and duration of melatonin nocturnal peak. A selective impairment of LH secretion was observed in both anorectic and obese patients. By considering together the two groups of patients and controls, a linear inverse correlation between the circadian mesor of plasma melatonin and the basal and LH-RH stimulated LH levels was found. The persistence of a certain melatonin secretion during the light hours in both anorectic and obese patients could play an inhibitory role on the pituitary gonadal function in these subjects.
TL;DR: The findings obtained with denervated pineal glands suggest that the regulation of pineal melatonin production by both α‐ and p‐adrenergic mechanisms is through receptors located on postsynaptic structures.
Abstract: The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal melatonin production was investigated in the Syrian hamster. The studies were conducted using organ cultured pineal glands collected from both anatomically intact and superior cervical ganglionectomized hamsters. Results obtained indicate that phenylephrine, an alpha-adrenergic agonist, by itself has no effect in promoting melatonin production; however, it potentiates the stimulatory effects of isoproterenol, a beta-adrenergic agonist, on pineal melatonin production in nonoperated hamsters. Similar observations were obtained with pineal glands whose presynaptic terminals were removed by prior superior cervical ganglionectomy. However, a longer incubation time was required (4-6 hours vs. 2 hours) with pineal glands taken from ganglionectomized animals. Apparently, beta-adrenergic activation is an absolute requirement to stimulate pineal melatonin production, and an alpha-adrenergic receptor mechanism potentiates beta-adrenergic activation. In addition, the findings obtained with denervated pineal glands suggest that the regulation of pineal melatonin production by both alpha- and beta-adrenergic mechanisms is through receptors located on postsynaptic structures.
TL;DR: In the Chinese hamster, the relationships between nuclear area and area of pinealocytes with time of day vary, depending on the age of animals as well as different photoperiodic conditions, although they differ only slightly.
Abstract: Semiquantitative electron microscopic observations on pinealocytes of the Chinese hamster (Cricetulus griseus) were made to compare the sizes of pinealocyte nuclei and pinealocytes as a whole, their nuclei and cytoplasm together, over a 24-hr period, between young animals (60-70 days old) and adult animals (120-130 days old) under LD 12:12 and between adults under LD 12:12 and LD 14:10. Under LD 12:12, similar 24-hr rhythms exist in the nuclear area and the area of pinealocytes of young animals, whereas in adults these values exhibit no significant 24-hr rhythm. In adults under LD 14:10, there is no significant 24-hr rhythm in the nuclear area, but the area of pinealocytes shows a statistically significant 24-hr rhythm. Thus, in the Chinese hamster, the relationships between nuclear area and area of pinealocytes with time of day vary, depending on the age of animals as well as different photoperiodic conditions, although they differ only slightly.
TL;DR: A daily rhythm in melatonin concentration in Harderian glands (HG) of female golden hamsters is described and is characterized by significant reductions following lights‐on, which do not appear to be affected by light or stress per se.
Abstract: A daily rhythm in melatonin concentration in Harderian glands (HG) of female golden hamsters is described and is characterized by significant reductions following lights-on. Concentrations in HG of intact or pinealectomized males are low and consistent over a 24-hour period. Castration of males is accompanied by increased levels of melatonin in the HG to approach those of females. When castrated males are exposed to short photoperiods, however, melatonin levels are typically low. Levels of serotonin (5-HT), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5-HIAA) are extremely variable in GH of both males and females, precluding definitive conclusions. Melatonin concentrations in HG of females do not appear to be affected by light or stress per se, nor are the superior cervical ganglia the pathway by which concentrations are modified.
TL;DR: This work demonstrates the activating effect of some indole compounds on 11 β‐hydroxylase and 17,20‐desmolase and the inhibitory effect of most of them on 11β‐hydroxysteroid dehydrogenase.
Abstract: The in vitro effects of 13 indole compounds on the synthesis of glucocorticoids and of adrenal androgens in sheep adrenal glands has been studied from 11-deoxycortisol as a precursor. This work demonstrates the activating effect of some indole compounds on 11 beta-hydroxylase and 17,20-desmolase and the inhibitory effect of most of them on 11 beta-hydroxysteroid dehydrogenase. Three categories could be distinguished: 1) compounds without any effect (5-hydroxytryptophan, 5-hydroxytryptamine); 2) compounds moderately increasing (10-30% as compared with controls) cortisol yields (tryptamine, melatonin, 6-hydroxymelatonin, 5-methoxytryptophol, indomethacin); and 3) compounds markedly increasing (80-100%) cortisol yields (5-methoxyindole acetic acid, 5-hydroxyindole acetic acid, 2-methylindole, 5-hydroxytryptophol, N-acetyl-5-hydroxytryptamine). In fact, since most of the studied indoles reduced 11 beta-hydroxysteroid dehydrogenase activity, the actual activation of cortisol synthesis was four to five times less. Lastly, all the studied compounds, but melatonin, increased the activity of 17,20 desmolase as seen from 11 beta-hydroxyandrostenedione and 11-ketoandrostenedione yields. The possible in vivo effects of the indoles for therapeutic use needs further studying.
TL;DR: A dense network of neuropeptide Y ( NPY)‐like immunoreactive (NPY‐LI) fibres was revealed in the ovine pineal gland at the light microscope level and had no effect on the stimulation of cAMP or melatonin synthesis by the adrenergic agonists.
Abstract: A dense network of neuropeptide Y (NPY)-like immunoreactive (NPY-LI) fibres was revealed in the ovine pineal gland at the light microscope level. The dorsal and peripheral regions of the gland contained the most dense concentration of NPY-LI fibres with relatively few fibres in the mid-region and almost none in the pineal stalk. The effect of NPY in conjunction with isoproterenol (ISO) on cyclic AMP (cAMP) accumulation and noradrenaline (NA) on melatonin synthesis was investigated using in vitro techniques. NPY had no effect on the stimulation of cAMP or melatonin synthesis by the adrenergic agonists.
TL;DR: The influence of pineal gland on the histopathologic changes induced in mammary glands by 7, 12-dimethylbenz(a)-anthracene (DMBA) has been studied.
Abstract: The influence of the pineal gland on the histopathologic changes induced in mammary glands by 7, 12-dimethylbenz(a)-anthracene (DMBA) has been studied. To achieve the maximum expression of pineal action in animals, 28-day-old female Sprague-Dawley rats were subjected to one of the following treatments: blindness + olfactory bulbectomy (BA), blindness + underfeeding (BU), or blindness + cold exposure (BC). Half of the rats in each group were also pinealectomized. Animals that were intact or only pinealectomized served as controls. Each animal received a single intragastrical dose of DMBA (20 mg) 4 weeks after performing the treatments mentioned above. At 28 weeks of age animals were sacrificed, and mammary tumors as well as mammary glands without macroscopic lesions were collected. Animals of the BU group failed to develop any tumors throughout the 20-week control period. In the remaining groups, tumors were found; the relation between number of adenocarcinomas (AC) and fibroadenomas was similar, always with a greater incidence of ACs. Some ACs showed areas with changes in the ductal epithelium that are considered signs of tumoral regression; pinealectomized animals had the lowest incidence of ACs with signs of regression. Ductule hyperplasia, considered as a premalignant lesion, was more frequent in pinealectomized rats than in controls and in animals with enhanced pineal function (BA, BU, and BC). Some nontumoral mammary glands showed dysplastic lesions; these lesions were less frequent in BU rats than in controls. We conclude that suppression of pineal function sensitizes the ductule cells to the initiation of neoplastic processes and hinders the development of regressive changes.
TL;DR: The ability of PHE to stimulate changes in melatonin release in the absence of concomitant changes in cyclic AMP indicates an important role for the α1‐receptor, while propranolol inhibits this response, providing evidence for adrenergic receptor interaction at a step other than cyclicAMP.
Abstract: Both alpha 1- and beta-adrenergic receptors are present on ovine pineals. In the rat these two receptors interact so that activation of the alpha 1-receptor potentiates the beta-receptor-mediated changes in cyclic AMP and the correlated changes in pineal N-acetyltransferase (EC 2.3.1.87). Here we investigate possible interactions between alpha 1- and beta-receptors through changes in cyclic AMP and assess the importance of each receptor to the melatonin response in ovine pineal punches/slices in vitro. The adrenergic agonists isoproterenol (ISO), noradrenaline (NA), and phenylephrine (PHE) stimulated dose-dependent changes in cyclic AMP with the order of potency of ISO greater than NA greater than PHE, consistent with their relative binding affinities for the beta-receptor. The beta-receptor antagonist, propranolol, showed dose-dependent inhibition of the ISO effect, whereas the alpha 1-selective antagonist, prazosin, had no effect. The S-shape of the stimulation and inhibition curves for ISO reflects cyclic AMP changes mediated by the beta-receptor only without interaction through the alpha 1-receptor. Each of the adrenergic agonists stimulated indistinguishable dose-dependent increases in melatonin release. The ability of PHE to stimulate changes in melatonin release in the absence of concomitant changes in cyclic AMP indicates an important role for the alpha 1-receptor. Prazosin inhibits this response, substantiating this conclusion. However, as propranolol is also inhibitory, it seems that the alpha 1-receptor response is absolutely dependent upon a small level of beta-receptor stimulation, thus providing evidence for adrenergic receptor interaction at a step other than cyclic AMP.
TL;DR: It is suggested that neonatal melatonin administration in pharmacological amounts induces precocious puberty as measured by vaginal opening and, furthermore, it advances the appearance of the first estrous smear with age‐dependent modifications of estrous cyclicity and prolactin and LH responses to EB.
Abstract: Melatonin (100 micrograms/rat) was administered to female rats on day 5 of life, 3 hours prior to the onset of darkness or at 12:00 hours Melatonin administration induced precocious puberty in both cases, as indicated by the advance of the time of the vaginal opening and the appearance of the first estrous smear as compared with controls (P less than 001), together with an increase in the number of estrous smears (P less than 005) and a reduction in the number of diestrous smears (P less than 005) Decreased serum prolactin levels were observed on day 21 of age (P less than 005) in melatonin-treated rats with both of the melatonin injection times as compared with controls No differences were apparent in basal luteinizing hormone (LH) levels either at 30 or at 60 days of age comparing melatonin- and vehicle-treated rats with either of the scheduled melatonin injection times As to serum follicle-stimulating levels (FSH) levels, there was a marked decrease in circulating FSH levels in melatonin-treated rats in both cases on days 21, 30, and 45 (P less than 005) as compared with controls A marked increase of serum prolactin at both 48 and 55 hours after estradiol benzoate (EB) administration was detected in 30-day-old melatonin-treated rats as compared with controls (P less than 005 for both points) Also, an increased responsiveness of prolactin to EB was found on the first day post-administration At 60 days of age, an increase in prolactin responses to EB was observed on the first day post-administration (31 and 48 hours after, (P less than 001), whereas no differences were detected at any other studied time The LH burst that occurs 31 hours after EB administration in 30-day-old rats was decreased in melatonin-treated animals as compared with controls (P less than 005) In 60-day-old melatonin-treated rats, a marked increase in the LH response to EB administration, 31 hours after injection (P less than 001), was observed These data suggest that neonatal melatonin administration in pharmacological amounts induces precocious puberty as measured by vaginal opening and, furthermore, it advances the appearance of the first estrous smear with age-dependent modifications of estrous cyclicity and prolactin and LH responses to EB
TL;DR: Experiments on isolated rat pinealocytes with the protein synthesis inhibitor cycloheximide indicate that tryptophan hydroxylase turns over rapidly in these cells, and this method will be valuable in studies of the adrenergic mechanisms regulating pineal tryptophile activity.
Abstract: A method for measuring tryptophan hydroxylase activity by assaying the product 5-HTP using high-performance liquid chromatography (HPLC) with electrochemical detection is described. A nocturnal elevation (80%) in rat pineal gland tryptophan hydroxylase activity was detected. Experiments on isolated rat pinealocytes with the protein synthesis inhibitor cycloheximide indicate that tryptophan hydroxylase turns over rapidly in these cells. This method will be valuable in studies of the adrenergic mechanisms regulating pineal tryptophan hydroxylase activity.