bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil elastase is involved in the initial destruction of human periodontal ligament
Authors: Ujiie Y. , Oida S. , Gomi K. , Arai T. , Fukae M.
Published: February 2007

Background and Objective:  It has been reported that noncollagenous proteins may provide mechanical strength to the periodontal ligament. Several proteolytic activities, including that of neutrophil elastase, are reported to increase significantly in periodontal disease. The aim of this study was to investigate the function of neutrophil elastase in the initial destruction of periodontal ligament at early stages of periodontal disease.

Material and Methods:  The detection and identification of proteinases in chronic periodontitis and healthy periodontal ligament were examined by zymographic and zymo‐Western analysis. The morphological changes of periodontal ligament, digested with or without authentic proteinases, were observed using scanning electron microscopy.

Results:  Increases in neutrophil elastase, plasminogen, and matrix metalloproteinase‐9 were detected in periodontal ligament from chronic periodontitis, compared with healthy periodontal ligament. Among these proteinases, only neutrophil elastase digested the intact noncollagenous proteins of periodontium. When human healthy periodontal ligament was directly digested by neutrophil elastase in an in vitro system, the morphological features were quite similar to that of the periodontal ligament in chronic periodontitis . In healthy periodontal ligament, the collagen fibrils are covered with noncollagenous proteins containing 110 kDa acidic glycoprotein, which was degraded initially by the neutrophil elastase.

Conclusion:  It was concluded that neutrophil elastase is involved in the degradation of noncollagenous protein‐covered collagen fibrils in the early destructive stages of periodontal disease.
Increases in Volume, Fluid Content, and Lens Weight of Eyes Following Systemic Administration of Melatonin
Authors: Quay W. B.
Published: February 2007

Melatonin's effects were studied in male golden hamsters (Mesocricetus auratus) distributed among five surgical groups (nonoperated, sham‐pinealectomized, sham‐pinealectomized plus black plastic shielding of the pineal region, pinealectomized, and pinealectomized plus black plastic shielding of the pineal region) and three injection groups (vehicle only, 25 μg melatonin, and 2,500 μg melatonin). Injections (s.c.) were daily for 28 d at L11 to L11.75 in a (light:dark) L:D 14:10 artificial photoperiod. Animals (N = 112) were killed and dissected on the day after the last injection (at 55–65 d of age). None of rhe surgical procedures affected weights of eyes or their parts, nor did they influence the effects of administered melatonin on the eyes. Melatonin caused an increase in absolute and relative eye weight and an increase in fluid content of intraocular space. The magnitudes of these effects were positively related to melatonin dose. These same eyes had a progressively lower weight of nonlenticular tissues with low to high doses of melatonin, probably in relation to greater fluid content, and suspected increase in intraocular pressure. Lens wet and dry weights were significantly greater in animals receiving melatonin, but only at the high dose. These actions of melatonin are likely to be direct and are shown to not require the presence of the pineal. Experiments of other designs are suggested in order to determine whether the effects of the low, near physiological, dose of melatonin represent physiological actions of endogenous melatonin, synthesized and released within the eye. However, effects of large doses of melatonin on the eye are still noteworthy in relation to interpretation of experiments employing such dosages, and of disease states involving changes in intraocular pressure.
Pinealectomy Has No Effect on Diet‐Induced Thermogenesis and Brown Adipose Tissue Proliferation in Rats
Authors: Viswanathan Mohan , George John C.
Published: February 2007

The role of the pineal gland in diet‐induced thermogenesis (DIT) and growth of brown adipose tissue (BAT) in rats during voluntary overfeeding was studied using pinealectomized and sham‐pinealectomized rats. Overfeeding was induced by offering the animals a cafeteria‐diet (CD) which contained a selection of highly palatable food items. Rats which were fed CD had significantly increased interscapular brown adipose tissue (IBAT) mass and increased tail‐skin temperature indicating the importance of the tail in thermoregulation during DIT. Pinealectomy had no effect on the increase in tail‐skin temperature and deposition of IBAT, which were stimulated by CD feeding. These findings suggest that the pineal is not directly involved in modulating the metabolism of BAT in rats.
Pineal Gland Morphology in Rats With Experimentally Induced Protein‐Calorie Malnutrition
Authors: Weaker Frank J. , Herbert Damon C.
Published: February 2007

The morphology of the pineal gland was studied in protein‐calorie‐malnourished (PCM) rats. Twenty‐day‐old male Sprague‐Dawley rats were placed in a 14:10 photoperiod and fed either an 8% low protein diet (LPD) or a standard laboratory diet (SLD) containing 27% protein for 30 d. At 50 d of age, rats from both animal groups were sacrificed at 0900 h and at 2400 h, and the pineal glands were immersion‐fixed for either light or electron microscopic analysis. The cytoplasm and nuclei of the pinealocytes from the SLD‐fed rats were consistently larger than those of the animals maintained on the LPD. Additionally, the lipid droplets were larger and more prominent in the controls at both 0900 h and 2400 h. Even though the size of these inclusions did not vary among animals given the same diet as a function of the time of sacrifice, they were more numerous in both the well‐fed and malnourished rats during the dark phase of the photoperiod. In contrast neither diet nor sampling time affected the size or number of pinealocyte mitochondria. These morphological observations lend further support to the premise than PCM impairs the cellular activity of the pinealocytes.
Daily Profiles of N‐Acetyltransferase Measured at a Single Time in Rat Pineal Glands, Retinas, and Harderian Glands
Authors: White Beatrix H. , Mosher Karen , Binkley Sue
Published: February 2007

Serotonin N‐acetyltransferase activity (NAT) exhibited a daily cycle in light:dark (LD) 14:10 when it was measured in pineal glands taken from rats killed at a sequence of time points. The ratio of peak subjective night NAT to minimum subjective day NAT was 10.9/0.3 nmol per pineal gland per hour. When the rats were placed in constant dark the rhythm persisted (8.2/0.02). When the rats were placed in constant light the rhythm persisted with markedly attenuated amplitude (0.6/0.02).

We also measured NAT profiles in rat pineal glands, Harderian glands, and retinas with alternative methods. We kept rats on six LD 14:10 light‐dark cycles with lights‐out beginning at midnight, 2 AM, 4 AM, 6 AM, 8 AM, or 10 AM and killing all the rats at one time point, 10 AM. We examined the NAT time profiles 4, 8, and 11 days following placement of the rats in the phase‐shifted cycles. In addition, we measured the NAT profile in LD 2:22 and LD 22:2 by keeping the rats on twelve cycles for 11 days and killing all the rats at one time.

Pineal NAT exhibited a rhythm in all the cycles: peak‐dark/nadir‐light values (nmol product per gland per hour) were 15.6/0.1 in LD 14:10, controls killed at successive time points. The ratios for the profiles obtained using the one time point procedure were 16.7/0.1 in LD 14:10 8.5/0.2 in LD 22.2, and 12.9/0.2 in LD 2.22. Increasing the photoperiod reduced the time to the NAT peak.

In LD 14:10, Harderian NAT was 31–39 nmol per gland per hour but the peak/ nadir radio was only 1.2; retinal NAT was low (0.2–0.7 nmol per retina per hour) and had only a 3.5‐fold peak/nadir ratio.
Electroconvulsive Shock: Effect on Pineal and Hypothalamic Indoles
Authors: McIntyre Iain M. , Oxenkrug Gregory F.
Published: February 2007

Chronic electroconvulsive shock (ECS) did not significantly alter pineal concentrations of melatonin. Statistically significant decreases of serotonin, however, were found in both the pineal and hypothalamus. These results support the previous reports of serotoninergic receptor supersensitivity following repeated ECS, and suggest serotoninergic involvement but do not necessarily exclude adrenergic involvement in the antidepressant effect of electroconvulsive therapy.
The Effect of Pinealectomy on Plasma Levels of Gonadotrophins and Growth Hormone in the Pigeon (Columba livid)
Authors: Rintamäki Hannu , Hissa Raimo , Balthazart Jacques , Scanes Colin G.
Published: February 2007

The effects of pinealectomy on plasma follicle‐stimulating hormone (FSH), luteinizing hormone (LH), and growth hormone (GH) concentrations were studied for a period of 9 weeks in pigeons reared under naturally increasing day length. After pinealectomy, plasma LH and GH concentrations decreased in both sexes when compared with sham‐operated birds. In pinealectomized female pigeons, the plasma level of FSH was elevated, while in male birds the effect on FSH was negligible. A trend toward increased weight of testis, ovary, and oviduct was also seen after pinealectomy, but the increase was not statistically significant.

The present results suggest that pinealectomy is able to modify the secretion of gonadotrophins and GH in the pigeon and indicate a stimulatory role for the pineal gland in LH and GH secretion and, in female pigeons, an inhibitory role in FSH secretion.
The Effects of Photoperiod and Melatonin on Serum Prolactin Levels of Mink During the Autumn Molt
Authors: Rose Jack , Stormshak Fredrick , Oldfield James , Adair John
Published: February 2007

An experiment was conducted to determine the effects of a reduced daily photoperiod and exogenous melatonin on serum prolactin levels of mink during the autumn molt and growth of the winter pelage. During the last week of June, adult standard dark female mink (Mustela vison) were exposed to natural changes in daylength (controls), a reduced photoperiod of 6 h light: 18 h dark (6L: 18D) or exposure to natural changes in daylength and treated with melatonin (10 mg) in a Silastic implant inserted subcutaneously over the scapular area. Beginning July 2, and continuing through October 22, blood samples were collected at nine biweekly intervals, and serum prolactin concentrations were quantified by a heterologous double antibody radioimmunoassay. Both reduced photoperiod and exogenous melatonin caused serum prolactin levels to decline rapidly after mid‐July, resulting in concentrations that were significantly lower than those of controls 6 to 8 wk earlier. These data suggest that growth of the winter pelage of mink is strongly associated with declining prolactin levels. It appears that part of the photoperiodic‐induced effects on fur growth of the mink are mediated through melatonin and its effects on prolactin synthesis and/or secretion.
Hamster and Rat Pineal Gland β‐Adrenoceptor Characterization With Iodocyanopindolol and the Effect of Decreased Catecholamine Synthesis on the Receptor
Authors: Craft C. M. , Morgan W. W. , Jones D. J. , Reiter R. J.
Published: February 2007

Rat and hamster pineal glands were used in binding studies to characterize their β‐adrenoceptors with a new specific antagonist ligand, iodocyanopindolol. The receptors were saturable, and the ligand was selective and demonstrated stereospecificity for both species. The rat pineal had a 20‐fold greater density of β‐adrenoceptors, while the affinity was one‐third that of the hamster pineal. Utilizing this radioligand, we examined the effects of decreased sympathetic input to the pineal on β‐adrenergic receptors in both species. Decreased noradrenergic input to the pineal gland of the hamster was accomplished by superior cervical ganglionectomy, or by exposing the animals to continuous light for 36 hours. Parallel studies were conducted with hamster pineal gland in which catecholamine synthesis was measured. The results indicate that a selective decrease in catecholamine synthesis in the hamster pineal does not change the β‐adrenoceptor density or affinity. In contrast, a concomitant increase in β‐adrenoceptor density but not affinity occurs in the rat pineal gland after similar decreased sympathetic input.
Evidence for Modulation of Melatonin Secretion in Men With Benign and Malignant Tumors of the Prostate: Relationship With the Pituitary Hormones
Authors: Bartsch Christian , Bartsch Hella , Flüchter Stephan‐Heribert , Attanasio Andrea , Gupta Derek
Published: February 2007

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4‐h intervals throughout a 24‐h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle‐stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean‐cosinor method, and linear correlation coefficients between the five hormones were calculated for each group.

Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty‐four‐hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups.

These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.
Antigonadal Actions of Olfactory and Light Deprivation. I. Effects of Blindness Combined With Olfactory Bulb Deafferentation, Transection of Vomeronasal Nerves, or Bulbectomy
Authors: Sánchez‐Barceló E. J. , Mediavilla M. D. , Sánchez‐Criado J. E. , Cos S. , Cortines M. D. G.
Published: February 2007

Olfactory bulbectomy is known to potentiate the antigonadal effects of light deprivation. However, the physiological interpretation of the effects of bulbar ablation is complex, since it simultaneously implies sequelae like: a) the loss of olfactory sensitivity (anosmia), b) the suppression of the accessory olfactory system (AOS), and c) the suppression of nonsensorial functions of the bulbs. To study the participation of these three mechanisms in the effects of bulbectomy + light deprivation, we compared, in 28‐day‐old male rats, the effects of olfactory bulb deafferentation (peripheral anosmia) with those induced by either olfactory bulbectomy or blocking the AOS, alone or associated with blindness.

As compared to the intact or blinded animals, both blinded deafferented (EA) and blinded bulbectomized (EB) rats showed various reductions in weights of body, testes, accessory sexual glands, and prostates; serum testosterone levels were also depressed. Testes of EA rats showed various degrees of alterations in spermatogenesis. The only difference between EA and EB groups was in the pituitary weight, significantly lower in EA rats.

Vomeronasal nerve transection by itself had no effect on the parameters examined, and when combined with blindness it did not result in further inhibition of reproductive function. These results indicate that the potentiation by bulbectomy of the antigonadal effects of light deprivation is anosmia‐dependent and not due to a loss of nonolfactory functions of the bulbs. Our experimental model of peripheral anosmia makes it possible to study light‐olfaction interactions without the interference of the brain lesions inherent in bulbectomy.
Antigonadal Actions of Olfactory and Light Deprivation. II. Effects of Pinealectomy or Melatonin Injections in Olfactory Bulb Deafferented or Bulbectomized Male Rats
Authors: Mediavilla M. D. , Sánchez‐Barceló E. J. , Sánchez‐Criado J. E. , Cos S. , Cortines M. D. G.
Published: February 2007

Since olfactory bulb deafferentation (peripheral anosmia) potentiates the antigonadal effects of light deprivation, we studied a) the pineal involvement in this action and b) whether peripheral anosmia might increase the response to melatonin injections.

Four‐week‐old male rats were used in two experimental series. The first included rats in which blindness + peripheral anosmia was associated with either pinealectomy or sham pinealectomy. In the second series, intact, olfactory bulb deafferented and bulbectomized rats received daily injections of either melatonin (50 μg) or the vehicle alone. In both experiments animals were killed at 10 weeks of age.

The reduction in the weight of accessory sexual glands and prostates, as well as in the serum testosterone levels, induced by blindness + peripheral anosmia was fully prevented by pinealectomy, whereas body and pituitary weight reduction induced by the dual sensory deprivation were only partially prevented. Melatonin produced no effects in intact animals whereas in rats with either peripheral anosmia or bulbectomy it reduced the weight of body, accessory sexual glands, and prostates. Serum testosterone levels were not modified in any case with melatonin treatment. From these results we concluded that the antigonadal effects of blindness + peripheral anosmia are pineal‐dependent, that peripheral anosmia sensitizes the neuroendocrine reproductive axis to the antigonadal effects of exogenous melatonin, and that the reduction in the weight of testosterone‐dependent organs induced by melatonin in bulbectomized or deafferented animals, together with the normal serum testosterone levels observed, suggests peripheral actions of melatonin of possible antiandrogenic nature.
Effects of Photic History and Illuminance Levels on Male Golden Hamsters
Authors: Hoffman Roger A. , Johnson Lucinda B.
Published: February 2007

Four‐week‐old male hamsters, born and raised in total darkness or in LD 14: 10 (hr) were exposed to several low levels of illumination for 14 weeks. Analyses showed that testicular weights were significantly affected by both photic history and illuminance levels. Animals born in the dark possessed larger testes than those born in LD cycles and, further, displayed less responsiveness to levels of illumination below those required to suppress pineal function. While gonadal responses to photic duration may be said to be “all or none,” those resulting from insufficient illuminance levels are seemingly graded. Thus, the pineal gland may act indirectly as a photodosimeter at low illuminance levels.
Quantitative Ultrastructural Analysis of Differences in Exocytosis Number in Adrenomedullary Adrenaline Cells of Golden Hamsters Related to Time of Day, Pinealectomy, and Intracellular Region
Authors: Kachi T. , Banerji T. K. , Quay W. B.
Published: February 2007

This research analyzed differences mainly in the incidence of exocytotic figures in adrenaline cells (A ‐ cells) in pinealectomized (PX), sham‐operated (SPX), and non‐operated (NO) adult male golden hamsters, with the aim of determining whether these parameters change with the time of day and following pinealectomy, and whether intracellular regional differences exist in such changes. Animals acclimated to a standardized light: dark (LD) 12:12 photoperiod were sacrificed at 11 h after the onset of light (L‐11h) and 1 h after the onset of darkness (D‐1h) (8 animals/group/time) at 28 days postoperation. The adrenal medullas were examined and analyzed morphometrically by electron microscopy. The number of exocytoses per unit length (NEL) and the exocytosis index (a rough index of the number of exocytoses per cell) were measured in PF (perivascular‐space‐facing) and non‐PF plasma membranes. NEL increased from L‐11h (NO: 0.040 ± 0.010, X̄± SE) to D‐1h (0.078 ± 0.012) in all three experimental groups (ANOVA: P < 0.005), showing over fourfold higher levels in PF than in non‐PF membranes. NEL in PF membranes in PX animals showed higher levels than those in NO and SPX animals (P < 0.025), but in non‐PF membranes, no differences owing to time of day or surgery were seen. Exocytosis indices were (1) higher at D‐lh than at L‐llh in all three experimental groups (P < 0.005), (2) similar in PF and non‐PF membranes in control groups, and (3) higher in PF membranes in the PX group than in either non‐PF membranes or PF membranes in control groups. In conclusion, the exocytosis number in A cells changes in relation to time of day, rising in early dark phase, and its rise following pinealectomy can be seen only in PF membranes.
Responsiveness of Pineal N‐Acetyltransferase and Melatonin in the Cotton Rat Exposed to Either Artificial or Natural Light at Night
Authors: Nürnberger Frank , Joshi Bhaskar N. , Heinzeller Thomas , Milin Josif , Reiter Russel J.
Published: February 2007

In three separate experiments, the effect of acute exposure to either artificial or natural light during darkness of pineal N‐acetyltransferase (NAT) activity and melatonin content was studied in the cotton rat (Sigmodon hispidus). The exposure of animals to an artificial‐light irradiance of 160,000 μW/cm2 during darkness for either 1 s, 5 s, or 30 min was followed by a precipitous decline in pineal NAT activity and melatonin content when measured at either 15 or 30 min after light onset. When cotton rats were acutely exposed to light at night for 5 s, irradiances of either 3.2, 32, 320, and 3,200 did not suppress either pineal NAT or melatonin 30 min later; however, if the 5‐s exposure had an irradiance of either 32,000 or 160,000 μW/cm2, the pineal enzyme activity and indole content were depressed. Moonlight, which had a maximal irradiance of 0.32 μW/cm2, was unable to suppress pineal NAT activity and melatonin content even when the animals were exposed to the moonlight for 30 min. The treatment of cotton rats with either norepinephrine or its agonist, isoproterenol, before their exposure to light at night retarded slightly the suppressive effect of light on the pineal constituents measured. Also, these drug treatments suppressed the pre‐exposure levels of both NAT activity and melatonin content in the cotton rat pineal gland.
Effect of Magnesium Ions on Rat Pineal N‐Acetyltransferase (EC 2. 3 1.5) Activity
Authors: Morton Dougal J. , James Michael F. M.
Published: February 2007

N‐Acetyltransferase (NAT) activity at night and following isoproterenol treatment in intact animals was higher in rats pretreated with magnesium than in controls. This effect was probably due to enhancement of agonist binding and/or adenylate cyclase activation caused by magnesium ions. A similar effect was observed in vitro, where magnesium increased norepinephrine‐stimulated NAT activity in organ‐cultured pineal glands, suggesting that magnesium acts primarily on the pineal gland as opposed to some other peripheral or central site. This enhancement of NAT activity by magnesium would presumably lead to increased melatonin production; and as melatonin has been shown to decrease serum magnesium levels, a negative feedback mechanism may exist.
Diurnal Variations of Benzodiazepine Binding in Rat Cerebral Cortex: Disruption by Pinealectomy
Authors: Acuña‐Castroviejo Dario , Lowenstein Pedro R. , Rosenstein Ruth , Cardinali Daniel P.
Published: February 2007

In a previous work, pinealectomy was found to depress benzodiazepine (BZP) receptor binding in cerebral cortex membranes of rats killed at noon. In order to assess the effect of pineal removal on diurnal variations of BZP binding site concentration and affinity, groups of intact, pinealectomized, or sham‐ pinealectomized rats (subjected to surgery 2 wk earlier) were killed at six different time intervals during the 24‐h cycle. BZP binding was assessed by Scatchard analysis of 3H‐flunitrazepam high‐affinity binding to cerebral cortex membranes. In intact and sham‐pinealectomized rats, a maximum in BZP receptor concentration was found at midnight. Pinealectomy blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon. No changes in the affinity of the binding sites for the radioligand were detected as a function of time of day or following surgery. In a doseresponse experiment for melatonin ability to restore the depressed BZP receptor concentration of cerebral cortex membranes of pinealectomized rats killed at noon, a minimal effective dose of 25 μg/kg body weight was obtained. These results further support a link between pineal activity and brain BZP receptors in rats.
Seasonal Changes in the Circadian Plasma Melatonin Profile of the Tammar, Macropus eugenii
Authors: McConnell S. J.
Published: February 2007

The circadian plasma melatonin profile of a marsupial, the tammar, was determined at various stages of the annual reproductive cycle. At 6–14 days after each of the solstices and equinoxes, six females were exposed to a photoperiod equivalent to the natural day length at these times. Serial blood samples were taken 8 days later at 2–4‐hourly intervals, and plasma melatonin concentrations were measured by radioimmunoassay. Melatonin concentrations were elevated during the dark phase of each photoperiod, and there were significant changes between the profiles in each season. The amplitude of the nocturnal rise was significantly higher (P < 0.05) during the breeding season after the summer solstice (peak 259.5 ± 26.8 pg/ml, mean ± SEM) and autumnal equinox (287 ± 53.2 pg/ml) compared to those during the nonbreeding season after the winter solstice (111.5 ± 10.5 pg/ml) and vernal equinox (154.5 ± 10.4 pg/ml). The duration of the nocturnal rise was significantly correlated (r=0.996, P < 0.01) with the length of the dark phase and so was shortest after the summer solstice and longest after the winter solstice. Either of these changes in amplitude or duration might provide the photoperiodic information that regulates the annual reproductive cycle of the tammar.
Effects of Short Photoperiod and Melatonin Treatment on Thermogenesis in the Syrian Hamster
Authors: Viswanathan Mohan , Hissa Raimo , George John C.
Published: February 2007

This study investigated whether short photoperiod or melatonin‐treatment could alter the thermogenic capacity of Syrian hamsters. Exposure of hamsters to short photoperiod and to exogenous melatonin treatment induced gonadal regression and hypertrophy of brown adipose tissue (BAT). Short photoperiod and melatonin‐induced BAT hypertrophy was not accompanied by any change in noradrenaline (NA) turnover in this tissue. The concentration of NA was significantly decreased in hypertrophied BAT, indicating that sympathetic innervation in BAT did not effect its hypertrophy. No improvement in nonshivering thermogenic capacity was noticed in hamsters with increased BAT mass. However, capability for shivering thermogenesis seemed to be enhanced in melatonin‐treated hamsters. These observations suggest that melatonin, in addition to mediating short photoperiod‐induced gonadal regression in the Syrian hamster, also brings about thermoregulatory adjustments necessary for hibernation.
Plasma Levels of Immunoreactive Melatonin, Estradiol, Progesterone, Follicle Stimulating Hormone, and β‐Human Chorionic Gonadotropin During Pregnancy and Shortly After Parturition in Humans
Authors: Pang S.F. , Tang P.L. , Tang G.W.K. , Yam A.W.C. , Ng K.W.
Published: February 2007

Plasma concentrations of immunoreactive melatonin, estradiol, progesterone, follicle stimulating hormone (FSH), and β‐human chorionic gonadotropin (βhCG) were studied between 1000 and 1230 h in 105 Chinese females during six periods of normal pregnancy and 1–5 min after normal delivery. We have also examined the midday levels of immunoreactive melatonin in the cord blood of fetuses and plasma collected 1–5 min after and 24 h after delivery from their mothers. Concentrations of hormone immunoreactivities were determined by radioimmunoassay, and distinct fluctuations of all hormones were recorded during pregnancy. In the pregnant females, there were significant negative correlations between 1) melatonin and estradiol, 2) melatonin and progesterone, 3) βhCG and progesterone, and 4) βhCG and estradiol, and positive correlations between 1) melatonin and FSH and 2) progesterone and estradiol. Furthermore, plasma melatonin levels in the cord blood demonstrated no sex difference and were significantly lower than and correlated positively with the levels in their mothers. Our results suggest that 1) sex steroids may inhibit and FSH may potentiate circulating melatonin levels in gravid women; 2) changes in the levels of melatonin during pregnancy may affect the in utero development of the human embryo; and 3) circulating melatonin in the mother may be the major source of blood melatonin in the fetus before parturition.
Hormonal Modulation of Pineal‐Mediated Seasonal Events: Effects of Thyroid or Gonadal Manipulations
Authors: Champney Thomas H.
Published: February 2007

The ability of various manipulations of the endocrine system to affect pineal mediated events was examined in the present studies. Male Syrian hamsters were analyzed for pineal‐induced gonadal regression and depressions in serum thyroxine and testosterone levels after treatments which altered thyroid or gonadal function. Hamsters were thyroidectomized, received thyroxine implants (5 mg), or were thyroidectomized plus implanted with thyroxine. The animals were exposed to short photoperiods (10L:14D) for 9 wk, and plasma hormone levels and gonadal status were determined at the end of the experimental period. Likewise, hamsters were castrated, received testosterone implants (5 mg), or were castrated plus implanted with testosterone, and subsequently were exposed to short photoperiods for 9 wk. These animals' responses to photoperiod exposure were compared to animals which received identical hormonal treatments but remained in long photoperiod (14L:10D). All of the hamsters responded to the photoperiodic treatments equally, regardless of the hormonal treatment. The results of these studies indicate that experimentally induced alterations in plasma thyroxine or testosterone levels are unable to prevent or attenuate the ability of the pineal to elicit gonadal regression in response to short photoperiod exposure.
Changes in the Daily Rhythm of Serum Testosterone Levels Following Superior Cervical Sympathetic Ganglionectomy in the Cold‐Exposed Rat: The Role of the Pineal
Authors: Peschke Elmar , Peschke Dorothee , Peil Jürgen , Rúzsaá Csilla , Mess Béla
Published: February 2007

The effect superior cervical sympathetic ganglionectomy (Gx) exerted on the daily rhythm of serum testosterone levels was investigated in cold‐exposed rats. Rhythmic changes in pineal and pituitary weights were also measured.

1. Exposure to cold (10°C for 72 h) resulted in a signficant decrease of serum testosterone level and in an increase of the pineal weight.

2. In neutral ambient temperature (24°C) Gx, 30 d after operation, led to a moderate, statistically insignificant increase of serum testosterone levels and to decreased pineal weights (statistically significant).

3. The reactions provoked by cold exposure were counteracted by Gx. Testosterone levels, as well as the pineal weight, showed no remarkable change in the Gx, cold‐exposed animals.

4. These results confirm our assumption that experimental manipulations of the pineal gland can provoke significant changes in the neuroendocrine system only under special loading circumstances, e. g., cold exposure. Sympathetic denervation of the pineal gland counteracts the cold‐induced decrease of testosterone levels by counteracting the pineal antigonadotropic activity.

5. The empirical regression curves of the investigated parameters indicate that Gx or cold exposure provide a shift in the upper and lower limits of the daily rhythm. Partly inverted rhythms were also observed.

6. The presented results are discussed in relation to the parallel changes previously described in serum thyroxin, cholesterol, thyrotropin (TSH), and pituitary TSH levels. Thyroidal‐gonadal interactions, as well as cold exposure as a stress‐generating factor, have been considered in the possible explanation of the data herein reported.
Circannual Oscillations of Thyroxine and Cholesterol Levels After Pinealectomy and Ganglionectomy Related to the Weight Changes of the Pineal, Pituitary, and Thyroid Glands
Authors: Peschke E. , Peschke D. , Peil J. , Mess B.
Published: February 2007

Circannual rhythms of thyroxine (T4) and cholesterol blood levels, as well as of pineal, pituitary and thyroid weights were compared in intact, pinealectomized (Px), and ganglionectomized (Gx) rats. Special emphasis was put on the similarities and differences between the effect of Px and of Gx exerted on the neuroendocrine regulation of thyroid function.

Animals were kept under changing lighting schedules simulating the natural seasonal conditions (December, L:D 8:16; June, L:D 16:8; March and September, L:D 12:12). Animals were killed 90 d after surgical interventions in the above‐mentioned 4 months. In each season, animals were killed at four time points of the daily rhythm, and the means of the four data of a single day were used for further analysis evaluating Circannual changes.

All the investigated five parameters showed a monophasic Circannual rhythm. The lowest T4 blood level was measured in summer; in contrast, cholesterol level and organ weights had a maximum in the same season of the year.

The annual mean value of T4 level was diminished, while cholesterol level and pituitary and thyroid weights were increased in Px and Gx animals. Pineal weight showed a decrease in the Gx animals. Both Px and Gx failed to influence the Circannual rhythms of the measured parameters. However, a significant T4‐decreasing effect of Px and Gx was observed in the second half of the year, whereas a cholesterol‐level‐increasing effect, as well as thyroid hypertrophy, was registered in the first half of the year. These results suggest a prothyroid function of the pineal gland.
Reentrainment of Rat Circadian Activity Rhythms: Effects of Melatonin
Authors: Redman Jennifer R. , Armstrong Stuart Maxwell
Published: February 2007

Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long‐Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5‐h advance of the LD cycle, six out of 15 rats injected daily with melatonin at the new dark onset reentrained by a phase delay of the activity rhythm. The remaining nine melatonin‐injected rats and 14 of the 15 control injected rats phase advanced. Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady‐state entrainment. In contrast, the effects of melatonin injections given at the end of both the old and new dark periods are difficult to interpret due to the effects of the injection procedure itself at these times. Following an 8‐h advance of the LD cycle, all melatonin‐injected rats phase advanced while all vehicle and uninjected control rats phase delayed when injections were given at the old dark onset. As has been found in other research areas, the time of day of melatonin administration appears to be a critical factor in its mode of action. It is yet to be established whether these results from the use of pharmacological doses of melatonin are indicative of endogenous melatonin's involvement in the circadian reentrainment mechanism.
Alterations of Temperature, Sleepiness, Mood, and Performance in Residents Are Not Associated With Changes in Sulfatoxymelatonin Excretion
Authors: Sharp K. H. , Vaughn G. M. , Cosby P. W. , Sewell C. E. , Kennaway D. J.
Published: February 2007

Residency training may disrupt normal sleep/wake cycles, resulting in mood and performance deficits and alterations in biological rhythms. To characterize such disturbances and determine whether they are associated with an alteration in the day/night pattern of melatonin excretion, measurements were obtained around‐the‐clock in seven male subjects, each studied in two 48‐h sessions. Session 1 was conducted during the week before beginning a residency, and session 2 at 6 months into a first‐year surgical residency. The mean time of the end of nocturnal sleep and the timing of the temperature rhythm were both (P <.01) approximately 2.3 h earlier in session 2 (vs. 1). The sleepiness rhythm and the overall mood score rhythm were also phase‐advanced (P <.05) in session 2. The mean value of mood around‐the‐clock was significantly worse due to increased anger, tension, confusion, depression, and fatigue in session 2. Vigilance, tested by simple reaction time, did not exhibit a 25‐h rhythm and was worse in session 2 with an increase (P <.05) in mean response latency < 1 s and an increase (P <.01) in lapse time (microsleep, > 1–s latency). The urinary cortisol rhythm exhibited a raised curve average value (mesor) in session 2 (vs. 1, P <.05), but no difference was revealed in amplitude or acrophase. Urinary excretion of Na+, K+, and CI‐ did not differ between sessions, though the Na+/K+ ratio peaked earlier in session 2(P <.05). The urinary 6‐sulfatoxymelatonin rhythm did not differ in timing, amplitude, or mesor between sessions. A residency training schedule can be associated with altered timing in rhythms of sleep, sleepiness, temperature, and mood and with deterioration of mood and performance without detectable alteration of the endogenous melatonin pattern as exhibited by the excretion rate of the principal urinary metabolite.
Quantitative Cytological Analysis of Functional Changes in Adrenomedullary Chromaffin Cells in Normal, Sham‐Operated, and Pinealectomized Rats in Relation to Time of Day: III. Nuclear Density
Authors: Kachi T. , Banerji T. K. , Quay W. B.
Published: February 2007

The sizes of adrenaline (A) and noradrenaline (N) cells in the adrenal medulla of nonoperated (NO), sham‐operated (SPX), and pinealectomized (PX) male rats (n = 126) were investigated by quantitative light microscopy. Animals were killed at eight time points during a standardized 24‐h, light‐dark (12:12) cycle 14 days after surgery. Nuclear densities were measured in semithin sections of eponembedded specimens, initially fixed with glutaraldehyde and OsO4. Major findings are as follows. 1) The mean size of adrenomedullary A cells throughout 24 h (P<0.001), especially in the dark phase (P<0.001) but not in the light phase, was larger in PX animals than in NO and SPX animals. There were no statistically significant differences in the size of N cells among the three experimental groups in either the dark phase or the light phase. 2) The sizes of A and N cells showed time‐of‐day changes in the NO and the SPX animals but not in the PX animals. The temporal relationship of 24‐h changes in the cell size tended to be different between A and N cells in the NO and the SPX animals but not in the PX animals. 3) The cell size was apparently larger in A cells than in N cells in each experimental group. Pinealectomy thus caused hypertrophy of A cells, especially in the dark phase, but not apparently hypertrophy of N cells. Concerning the pinealectomy effects in relation to the time of day, the results support the hypothesis of pineal action being phase‐tuning and coordinating of at least some circadian systems.
Rapid Adjustment of the Pineal N‐Acetyltransferase Rhythm to Change From Long to Short Photoperiod in the Japanese Quail (Coturnix coturnix japonica)
Authors: Zeman Michal , Illnerová Helena
Published: February 2007

The dynamics of adjusting the pineal N‐acetyltransferase rhythm from long to short photoperiod was assessed in the Japanese quail (Coturnix coturnix japonica). The transition from LD 16:8 to LD 8:16 was accomplished by symmetrical prolongation of the dark period. In LD 16:8, the period of elevated nocturnal activity lasted approximately 7 hours. During the first prolonged night, the evening N‐acetyltransferase rise advanced by almost 3 hours relative to the rise in LD 16:8 and occurred at the same time as during the 3rd, 7th, and 14th day after the transition. The morning N‐acetyltransferase decline did not shift during the first long night; during the third night it was delayed relative to the decline in LD 16:8 by more than 2 hours and occurred at the same time as during the 7th and 14th night following the LD 16:8 to LD 8:16 transition. Three, 7, and 14 days after the transition, the period of elevated N‐acetyltransferase activity lasted approximately 12 hours. Hence extension of the N‐acethyltransferase rhythm profile proceeded first into the evening and then only into the morning hours, and it was accomplished within 2 to 3 days.
Effects of Melatonin and 6‐Methoxybenzoxazolinone on Photoperiodic Control of Testis Size in Adult Male Golden Hamsters
Authors: Anderson Keith D. , Nachman Ronald J. , Turek Fred W.
Published: February 2007

Consumption of young plants containing 6‐methoxybenzoxazolinone (6‐MBOA) appears to play an important role in the initiation of reproduction each spring in wild populations of the montane vole. Following its identification, 6‐MBOA has been found to stimulate the reproductive system in a number of rodent species, but the mechanism of action remains unknown. The chemical structure of 6‐MBOA is similar to melatonin, which, in addition to its well‐known antigonadal effects, can exert a progonadal influence under certain experimental conditions. To determine if 6‐MBOA might act as a melatonin agonist, four experiments were conducted to compare the effect of these two compounds on testis size in the golden hamster, a rodent whose responses to melatonin are well characterized. 1) Hamsters exposed to 14 h light per day (14L: 10D) received a daily injection of melatonin (25.0 μg) or 6‐MBOA (17.8 μg). 2) Hamsters exposed to 6L: 18D received Silastic capsules (50 or 200 mm) containing melatonin or 6‐MBOA. 3) Hamsters exposed to 6L‐.18D received chow containing melatonin (21.1 or 42.2 μg/gm chow) or 6‐MBOA (15.0 or 30.0 μg/gm). 4) Hamsters exposed to 6L: 18D received drinking water containing melatonin (15.5 μg/ml) or 6‐MBOA (11.0 μg/ml). Testis widths were determined at 2–3 week intervals, and after 66–73 days testes were removed and weighed. Melatonin significantly influenced testis size in each experiment, but treatment with 6‐MBOA had no effect in any of these experimental paradigms, indicating that 6‐MBOA does not act as a melatonin agonist in the hamster. However, these results indicate that the consumption of melatonin (and presumably melatonin agonists) could serve as an environmental stimulus for reproductive activity.
Effects of Photoperiod on (he 24‐Hour Melatonin Profiles of the Bennett's Wallaby (Macropus rufogriseus rufogriseus)
Authors: Curlewis J. D. , Loudon A. S. I.
Published: February 2007

The Bennett's wallaby is a seasonal breeder in which photoperiod is an important proximate factor involved in regulating the timing of the breeding season. The present study was undertaken in order to describe the melatonin profiles of female wallabies under natural photoperiod and to examine the effects of abrupt changes in day length on the melatonin profile. Under artificial and natural photoperiods, plasma melatonin concentrations were low or nondetectable during the day but increased after the onset of darkness to values of up to 50 pg/ml. Under natural photoperiod, melatonin profiles were obtained from animals on December 17, April 3, June 26, and October 7. The duration of the nocturnal melatonin rise was positively correlated with the duration of the night, and there was no significant effect of time of year on the amplitude of the nocturnal melatonin peak. In a further study, 12 animals were placed in 9L: 15D and after 7 days, one‐half were transferred to 18.5L: 5.5D for 6 weeks. Before and after each change of photoperiod, melatonin profiles were obtained from both groups. As demonstrated for animals on natural photoperiod, duration but not amplitude of the nocturnal melatonin rise was affected by day length. It is noteworthy that two of the 17 animals used in this study did not show evidence of a nocturnal rise in melatonin levels.
Long‐Term Effects of Pinealectomy on Testicular Function, Luteinizing Hormone‐Releasing Hormone Hypothalamic System, and Plasma Prolactin Levels in the Mink, a Short‐Day Breeder
Authors: Boissin‐Agasse L. , Jacquet J. M. , Lacroix A. , Boissin J.
Published: February 2007

Experiments in minks, as in a number of other seasonal breeders, clearly demonstrate that the pineal gland is essential for the photoperiodic control of reproduction. While maintenance of pineal‐intact minks under natural photoperiods results in a set of seasonally appropriate changes in testicular activity, pinealectomized minks undergo none of these changes but rather remain sexually inactive as under long‐day conditions. Thus, the consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length.

Although the precise mechanism by which the pineal regulates hypothalamic‐pituitary gonadal function remains unknown, the results of the present study indicate that, in the mink, luteinizing hormone‐releasing hormone axonal transport is affected by pinealectomy.

Furthermore, our results suggest that the pineal does not act exclusively upon the neuroendocrine‐gonadal system but also acts on other functions that are influenced by photoperiod. Pinealectomized minks left in natural conditions cannot adjust their prolactin secretion in response to either long or short photoperiods. Operated animals continued to have plasma prolactin variations but at irregular intervals and with no apparent relation to the time of the year. The data strengthen the hypothesis that melatonin may act at some point on the hypothalamic neuroendocrine systems, which regulate the two functions differently, and that melatonin is not an anti‐ or progonadal substance but rather a seasonal transducer.
Unusual Configurations of Endoplasmic Reticulum in Pinealocytes of the Djungarian Hamster (Phodopus sungorus)
Authors: Fechner Jorg
Published: February 2007

Ultrastructural observations of the pineal gland of Phodopus sungorus revealed different morphological forms of endoplasmic reticulum. These included crystalloids composed of 200Å‐wide tubules with an intervening space of 200Å and connected at right angles to form a rectangular lattice; complexes of undulating 500Å‐wide tubules in an electron‐dense cytoplasmic matrix; and stacks of flattened cisternae covered with granular electron‐dense material. All these structures are continuous with the surrounding endoplasmic reticulum. Frequently one structure is directly connected with another. The exact function of these structures derived from the endoplasmic reticulum is still unclear, but they can be assumed to be morphological features of augmented secretory activity.
A Study of the Mutagenicity of Melatonin and 6‐Hydroxymelatonin
Authors: Neville Sally , Arendt Josephine , Ioannides Costas
Published: February 2007

The mutagenicity of melatonin and its major metabolite 6‐hydroxymelatonin were evaluated using the Ames test and three strains of Salmonella typhimurium‐TA 97, TA 98, and TA 100. Neither compound exhibited mutagenicity whether in the presence or absence of an activation system derived from rats induced with Aroclor 1254. Positive controls were employed throughout and gave the expected response. We conclude that melatonin, 6‐hydroxymelatonin, and their microsomal metabolites are not mutagenic in the Ames test.