bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Pinealectomy on Liver Insulin and Glucagon Receptor Concentrations in the Rat
Authors: Rodríguez Victoria , Mellado Consuelo , Alvarez Elvira , De Diego Juana G. , Blázquez Enrique
Published: February 2007

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 insul in 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.
Presence of Melatonin in the Umbilical Cord Blood of Full‐Term Human Newborns
Authors: Vicente Purificación , García Adoración , Alvarez Elvira , Clemente Samuel , Blázquez Enrique
Published: February 2007

The present study was designed to determine whether melatonin circulates in the umbilical cord blood of healthy human newborns and whether the concentrations of this hormone follow a circadian rhythm at birth. Umbilical cord blood was collected from full‐term human newborns at the time of delivery. Serum melatonin was extracted with diethylether and determined by radioimmunoassay by using radioio‐dinated melatonin and rabbit antimelatonin antiserum. Significant amounts of melatonin were detected in the sera obtained from umbilical cord blood. When serum melatonin concentrations of human newborns were represented over 6‐h periods or hour by hour over the 24 h of 1 d, similar hormone concentrations were found consistently. These results indicate that melatonin is present in quite high levels in the umbilical cord blood, which may be at least in part, of maternal origin. Also, our results suggest the absence of a melatonin circadian rhythm in human newborns, which may reflect an immaturity of the components involved in melatonin synthesis.
Seasonal Differences in Glucose Tolerance and Insulin Response of Pinealectomized Pigeons (Columba livia)
Authors: Ramachandran A.V. , Patel M.M.
Published: February 2007

The effects of a glucose tolerance test (GTT) and an insulin response test (IRT) on blood glucose levels were evaluated in pinealectomized and nonpinealectomized pigeons during the breeding and nonbreeding months. The tests revealed increased glucose tolerance and insulin sensitivity in pinealectomized birds during the breeding season. In the nonbreeding season, both the pinealectomized and the control birds tended to show more or less similar responses for both GTT and IRT. These changes confirm the anti‐insulin role of the pineal in wild pigeons during the breeding season and the possible significance of the pineal gland in modulating seasonal changes in carbohydrate metabolism.
Plasma Prolactin Concentrations in Pinealectomized Ewes Receiving Melatonin Treatment and in Pineal Intact Ewes Maintained Under a Non‐24‐Hour Photoperiod
Authors: Poulton A.L. , English J. , Symons A.M. , Arendt J.
Published: February 2007

We have investigated the profiles of prolactin secretion in relation to onset of breeding activity in Suffolk‐Cross ewes with artificially modified melatonin rhythms. With treatments commencing in midsummer, groups of ewes were 1) subjected to a 8L:16D photoperiod, 2) maintained under a “short” (6L:16D) photoperiod repeated over a 22‐h cycle that induces an elevation in plasma melatonin that does not endure for the entire dark phase, 3) pinealectomized (pnx) to abolish plasma melatonin levels, and 4) pinealectomized and treated with a melatonin implant (subcutaneous) to provide a constant (no 24‐h rhythm) elevation in plasma melatonin. The onset of breeding activity was significantly advanced in both the 8L:16D and pnx/implant groups compared to the 6L:16D and untreated pnx ewes. The two latter groups displayed a normal timing in seasonal breeding activity. Low and high plasma prolactin levels corresponded with short and long photoperiods during both the 24 and 22‐h cycles. There was no clearcut “seasonal” rhythm in plasma prolactin in either of the pnx groups. A clear differentiation was seen between reproductive response and prolactin response, particularly in the case of ewes monitored on 22‐h cycles of short photoperiod.
Neuropeptide Y‐Containing Neurons in the Rat Superior Cervical Ganglion
Authors: Reuss Stefan , Moore Robert Y.
Published: February 2007

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.
Influence of Subchronic Intake of Melatonin at Various Times of the Day on Fatigue and Hormonal Levels: A Placebo‐Controlled, Double‐Blind Trial
Authors: Nickelsen Thomas , Demisch Lothar , Demisch Klaus , Radermacher Barbara , Schöffiing Karl
Published: February 2007

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.
Activity of Melatonin and Other Pineal Indoles on the In Vitro Synthesis of Cortisol, Cortisone, and Adrenal Androgens
Authors: Touitou Yvan , Bogdan André , Auzéby André , Touitou Catherine
Published: February 2007

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 11β‐hydroxylase and 17,20‐desmolase and the inhibitory effect of most of them on 11β‐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 11β‐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 11β‐hydroxyandrostenedione and 11‐ketoandrostenedione yields. The possible in vivo effects of the indoles for therapeutic use needs further studying.
Effects of Pinealectomy and Continuous Light on Mating Behavior of Male Rats
Authors: Urquijo M.D. Colmenero , López B. Díaz , Menéndez‐Abraham E. , Fernández B. Marín
Published: February 2007

The role of pinealectomy and continuous light in the regulation of sexual activity was studied in the male rat. The parameters studied in order to evaluate the sexual behavior were initial latency, ejaculatory latency, refractory period, neuromotor activity, number of ejaculations, intromissions (false, real, and total) and percentage of ejaculating male rats. Pinealectomy as well as continuous light induced a marked facilitation of the animal's sexual behavior as shown by the shorter initial latency and refractory period, as well as by the increase in the number of intromissions (real and total) showed in the tests. However, the ejaculatory latencies did not change. There was also an enhanced neuromotor activity. An increase in the number of ejaculations as well as in the percentage of ejaculating male rats was produced by continuous light. From the results it is concluded that pineal hormones play an important role in male rat sexual behavior.
Circannual Serum Creatine Kinase Patterns After Ganglionectomy and Pinealectomy of the Wistar Rat
Authors: Peschke Dorothee , Peschke E. , Peil J. , Mess B.
Published: February 2007

Previous investigations have shown that an inverse correlation exists between serum thyroxine levels (T4) and serum creatine kinase activity (CK) both in hypothyroid and hyperthyroid states. In the present study, serum T4 levels and total serum CK activity were analysed after thyroidectomy (TX), ganglionectomy (extirpation of the superior cervical sympathetic ganglion) (GX), or pinealectomy (PX) four times a year (March, June, September, and December). Blood samples were taken four times daily (at midlight, middark, and at 1 hour after the onset of the light and dark periods). Animals were kept under an artificial light schedule that simulated natural light‐dark periods. The annual main values of serum T4 levels were significantly decreased after the operations, whereas serum CK activities were increased. Our circannual investigations demonstrated an inverse correlation between serum T4 levels and total serum CK activity (under hypothyroid circumstances). In addition, the circannual pattern of the serum CK activity demonstrated maxima under short‐day (winter) conditions and minima under long‐day (summer) conditions. GX and PX provoke an unimportant shift (a little longer than 2 months) in maxima and minima of the annual rhythm. Circannual curves exhibited differences in the degree of the increase of serum CK activity of GX and PX groups. These results indirectly confirm the assumption that experimental sympathetic denervation or removal of the pineal gland will induce a hypothyroid state over the long term.
Presence of a Distinct 24‐Hour Melatonin Rhythm in the Ventricular Cerebrospinal Fluid of the Goat
Authors: Kanematsu Nobue , Mori Yuji , Hayashi Shinji , Hoshitio Kunio
Published: February 2007

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 μg/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 μg 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.
Melatonin Response to Exercise Training in Women
Authors: Skrinar Gary S. , Bullen Beverly A. , Reppert Steven M. , Peachey Sharon E. , Turnbull Barry A. , McArthur Janet W.
Published: February 2007

Previous human stuthes 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‐l), 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‐l and T‐3. Plasma melatonin, epinephrine, and norepinephrine levels rose significantly (P < .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‐l 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.
Entrainment of the Rhythm in Thymidine Incorporation by Cultured Chick Pineal Glands
Authors: Wainwright S. D. , Wainwright Lillian K.
Published: February 2007

Young chicks were raised under a standard cycle of illumination and their pineal glands were cultured in organ culture. We have already reported a rhythmic daily cycle in the cumulative incorporation of thymidine into DNA when the glands were incubated under the cycle of illumination to which they were entrained in vivo. Incorporation ceased shortly after the end of the photoperiod and resumed again at, or shortly after, start of the following photoperiod. We have now shown that this cycle was entrained to other lighting schedules and largely unaffected by the time of explanting into culture. The rhythm also persisted in glands cultured in constant darkness. However, when the cycle was maintained by daily renewal of the culture medium it was markedly affected by changes in the time of day at which medium was renewed. Results for glands cultured under constant illumination were inconsistent.
Posthatch Day/Night Differences in Synaptic Ribbon Populations of the Chick Pineal
Authors: Robertson George N. , Dickson D. Howard , Jackson Patrick C.
Published: February 2007

Pineal synaptic ribbon (SR) populations of the early posthatch white leghorn chick were counted to determine if they demonstrate a rhythm that is in accordance with the light/dark cycle. SRs were counted between day 7 and day 10 and on day 14 of posthatch development, with samples at midlight, middark (14L:10D), and constant darkness. SR populations did not exhibit significant changes on days 7 and 8 under cycled lighting conditions nor on days 9 and 10 under constant darkness. A second experiment demonstrated that the dark:light ratio of SR populations of day 14 chicks, under cycled lighting, was 3.4:1.0, indicating SR rhythmicity by that stage of development. In that a preliminary experiment had demonstrated a 4.2:1.0 darklight ratio in SR populations in a predominantly day‐10 population of chicks, we believe that SR rhythmicity begins on, or near, day 10 of posthatch development. To determine if the invasion of sympathetic fibers from the superior cervical ganglion (SCG) correlates with the initiation of SR light/dark population differences, we employed tyrosine hydroxylase immunofluorescence to reveal the distribution of catecholaminergic fibers in chick pineal follicles Follicular innervation doubled over the day 7 to day 14 period, during which time light/dark differences in SR populations were established. There is a correlation, in time, between the invasion of the pineal by the sympathetic fibers and the initiation of SR light/dark differences. The circadian rhythm of pineal N‐acetyltransferase (NAT) activity, the rate‐limiting enzyme in the melatonin pathway, is established earlier (day 2) than the light/dark differences in SR populations (day 10). It is possible that SR rhythmicity is influenced by the ingrowth of the pineal sympathetic innervation, and that SRs respond to an extrapineal oscillator rather than the independent oscillators of the chick pineal responsible for the rhythm of NAT activity and melatonin synthesis.
Circadian Rhythms of Human Pineal Melatonin, Related Indoles, and Beta Adrenoreceptors: Post‐Mortem Evaluation
Authors: Oxenkrug G. F. , Anderson G. F. , Dragovic L. , Blaivas M. , Riederer P.
Published: February 2007

Human pineal glands obtained from 77 post‐mortem sources from various age groups and times of death were used to examine the 24‐hour cycle of serotonin (5‐HT), melatonin, N‐acetylserotonin (NAS), and beta adrenoceptor density. Pineal glands were divided sagitally and a single half was used to measure 5‐HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes. The results show that density of pineal beta adrenoceptors was relatively constant between midnight and 18.00 h and became significantly higher between 18.00 and 20.00 h as measured by ligand saturation binding experiments using (125‐1) iodocyanopindolol. The receptor affinity of all of the samples assayed remained in relatively narrow range near 58 pM and only changes in the relative receptor density were apparent. The up‐regulation of receptors coincided with an increase in the concentration of 5‐HT that began to rise between 16.00 and 20.00 h and became maximal between 20.00 and midnight. NAS, the immediate precursor of melatonin, was also at maximal levels between 20.00 h and midnight. Both 5‐HT and NAS began declining after midnight and this change corresponded to the maximal pineal gland concentration of melatonin between midnight and 4.00 h. It is therefore suggested that the up‐regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5‐HT and the subsequent conversion to NAS. These events are followed by the highest accumulation of melatonin after midnight and represent the synthesis of melatonin from its precursor NAS in a sequential pattern.
The Effect of Sleep/Wake State on Nocturnal Melatonin Excretion
Authors: Morris Mary , Lack Leon , Barrett Judy
Published: February 2007

Twenty‐four hour patterns of urinary 6‐sulphatoxymelatonin excretion were monitored in eight healthy adult subjects in two bed rest constant routines, one with normal nocturnal sleep and one with continuous wakefulness. The implementation of dim light “constant routines” enabled the effect of the sleep wake/state on melatonin to be tested without the confounding effects of body activity and normal room lighting. In both conditions 6‐sulphatoxymelatonin excretion was significantly higher during the nighttime hours (2200‐1000) than during the daytime hours (1000‐2200) producing averages of 80% and 78.5% of the total 24 hour output in the sleep and wakeful conditions, respectively. The large differences between subjects in nocturnal melatonin excretion (38 to 150 nmol) were highly consistent between the two conditions. There were no differences between the nocturnal wakeful and sleep conditions in total nighttime melatonin excretion nor in the nighttime percentage of the 24 hour total melatonin excretions. Therefore, the sleep/wake state alone had no effect on nocturnal melatonin excretion. On the other hand, a significant correlation between the nighttime melatonin percentage and sleep length suggested the need to investigate further the relation between the amplitude of the melatonin circadian rhythm and sleep length and quality.
Some Properties of Pineal Gland Hydroxyindole‐O‐Methyltransferase From Black Rhinoceros (Diceros bicornis)
Authors: Morton Dougal J. , Kock Nancy
Published: February 2007

Pineal glands were obtained from two young female black rhinoceri that had died as a result of postcapture trauma during a translocation exercise. Hydroxyindole‐O‐methyltransferase (HIOMT) from these pineal glands showed a peak activity at pH 8.2, although high activity extended over a fairly wide pH range (7.8–8.4). N‐acetylserotonin was the best hydroxyindolic substrate for the enzyme, although other hydroxyindoles were methylated, the relative affinities being similar to values previously reported for bovine HIOMT. Kinetic analyses revealed that black rhinoceros HIOMT was subject to substrate inhibition by both substrates at high concentration; this observation is unlikely to have physiological significance. The catalytic mechanism was found to be ordered Bi‐Bi, in which S‐adenosylmethionine is the obligatory first substrate to bind to the enzyme, such binding allowing for binding of the hydroxyindolic substrate followed by catalysis, products again leaving the catalytic site in a sequential fashion.
Mechanisms Controlling the Offset of Melatonin Secretion in the Ewe
Authors: Earl C. R. , D'Occhio M. J. , Kennaway D. J. , Seamark R. F.
Published: February 2007

Melatonin secretion was investigated in ewes maintained in continuous darkness for 6 days and following an acute delay of lights off as part of a study offactors controlling the melatonin rhythm. In continuous darkness, the interval between successive offsets in circulating melatonin was always greater than 24 hr, indicating that the decline in melatonin secretion in sheep is controlled by endogenous mechanisms having a period longer than 24 hr. In ewes placed under extended darkness with no delay in the time of lights off, the decline in circulating melatonin was delayed by 2.5 ± 0.2 hr. Animals that had dusk delayed by 4 hr continued to secrete melatonin for at least 4 hr after subjective lights on. Under these conditions, it is proposed that the offset of melatonin secretion is influenced by the timing of lights off and the onset of melatonin secretion. The brain centers controlling melatonin secretion in sheep appear to operate in a manner similar to several species, and thus the sheep may prove to be a useful experimental animal for further studies of circadian mechanisms.
Permeability of the Pineal Gland of the Viscacha (Lagostomus maximus maximus) to the Lanthanum Hydroxide
Authors: Domínguez Susana , Piezzi Ramón S. , Scardapane Luis , Guzmán Jorge A.
Published: February 2007

Lanthanum hydroxide together with a fixative solution was injected into the third ventricle of the viscacha. The tracer penetrated freely into the pineal gland demonstrating an extensive network of intercommunicating intercellular spaces. Numerous gap junctions were observed indicating that they are the predominant interparenchymal contacts. The capillaries were characterized by non‐fenestrated endothelial cells lining a moderate‐sized perivascular space. Precipitates of lanthanum hydroxide were found in the basal membranes of the perivascular and interendothelial spaces, but not in the vascular lumina. The tracer stopped at tight junctions; these constitute a barrier between the pinealocytes and the blood compartment. Active micropinocytosis observed in the capillary walls suggests a transendothelial transport.
Evidence for an Effect of ELF Electromagnetic Fields on Human Pineal Gland Function
Authors: Wilson Bary W. , Wright Cherylyn W. , Morris James E. , Buschbom Raymond L. , Brown Donald P. , Miller Douglas L. , Sommers‐Flannigan Rita , Anderson Larry E.
Published: February 2007

A study was carried out to determine possible effects of 60‐Hz electromagnetic‐field exposure on pineal gland function in humans. Overnight excretion of urinary 6‐hydroxymelatonin sulfate (6‐OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6‐OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6‐OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.
Scanning electron microscopic study on pineal vascularization of the common tree shrew (Tupaia glis)
Authors: Chunhabundit Panjit , Somana Reon
Published: February 2007

Chunhabundit P, Somana R. Scanning electron microscopic study on pineal vascularization of the common tree shrew (Tupaia glis). J Pineal Res 1991 : 1059‐64.

The detailed blood supply including microvascularization of pineal gland in the common tree shrew (Tupaia glis) was investigated using a vascular corrosion cast technique in conjunction with scanning electron microscopy. Adult common tree shrews of both sexes, divided into 3 groups, were injected with red latex, blue vinyl resin, and Batson's No. 17 plastic mixture for the studies of arterial supply, venous drainage, and microvasculature of the pineal gland, respectively. It was found that the pineal gland is a highly vascularized organ. It receives two to four branches from the medial posterior choroidal arteries. Two types of capillary arrangements, fan‐like and network, are observed. As in the human, usually one and occasionally two pineal veins, draining directly into the great cerebral vein of Galen, are observed. A pineal portal system is not demonstrated.
Differential effects of pinealectomy on amygdala and hippocampus serotonin metabolism
Authors: Miguez Jesús , Martin Francisco , Aldegunde Manuel
Published: February 2007

Miguez J, Martin F, Aldegunde M. Differential effects of pinealectomv on amygdala and hippocampus serotonin metabolism. J Pineal Res 1991 : 10: 1 W103.

The purpose of the present study was to determine the effects of long‐term pinealectomy on serotonin metabolism in the amygdala and the hippocampus of male rats. Pinealectomy did not significantly alter either tryptophan or serotonin concentrations in the amygdala or the hippocampus. However, statistically significant decreases in 5‐hyroxyindole‐3‐acetic acid levels and tryptophan hydroxylase activity were found in the amygdala. Monoamine oxidase activity was unchanged in both regions. These results support the involvement of the amygdaloid serotoninergic system in mediating the functions of the pineal gland.
Long‐term pinealectomy alters hypothalamic serotonin metabolism in the rat
Authors: Míguez Jesús , Martín Francisco , Míguez Isabel , Aldegunde Manuel
Published: February 2007

Abstract: In the present study, the effects of long‐term pinealectomy on tryptophan, 5‐hydroxytryptamine (5‐HT or serotonin), 5‐hydroxy‐3‐indoleacetic acid (5‐HIAA), and tryptophan hydroxylase and monoamine oxidase activities were studied in preoptic area‐anterior hypothalamus (POA‐AH) and in the medial and posterior hypothalamus of the rat. After pinealectomy, 5‐HT levels decreased significantly in medial hypothalamus but increased in the POA‐AH. The levels of 5‐HIAA decreased significantly in the POA‐AH and medial hypothalamus. Tryptophan levels remained unchanged while tryptophan hydroxylase activity diminished significantly in POA‐AH and medial hypothalamus. Monoamine oxidase activity remained unchanged in the hypothalamic regions. These results suggest that pinealectomy induces differential inhibitory actions on the serotoninergic terminal regions, mainly in anterior and medial hypothalamic areas.
Pineal rhythm of N‐acetyltransferase activity and melatonin in the male badger, Meles meles L, under natural daylight: Relationship with the photoperiod
Authors: Charron G. , Souloumiac J. , Fournier M.C. , Canivenc R.
Published: February 2007

Abstract: The rhythmicity of melatonin secretion and of pineal NAT activity was compared in male badger kept in natural daylight during two distinctly different photoperiods (January and June). The hormone and its enzyme follow the same pattern with a nighttime elevation and a low level during the day, demonstrating the presence of a nyctohemeral rhythm. The high correlation found between the NAT activity and the melatonin concentration suggests that NAT is the rate‐limiting enzyme in melatonin synthesis in the badger. Peak amplitudes were similar under the two photoperiods. Melatonin secretion occurred in the first part of the night irrespective of the photoperiod. The rhythm of melatonin secretion is modified by the photoperiod. The duration of high nighttime levels varies; it is longer (8 h) when the night is long (16 h) in January, and shorter (6 h) when the night is short (8 h) in June. In the badger, differences in the duration of high level melatonin at night may reflect variations in day length and convey to the animal the photoperiodic information.
Pineal melatonin concentrations during day and night in the adult hedgehog: Effect of a light pulse at night and superior cervical ganglionectomy
Authors: Saboureau Michel , Vivien‐Roels Berthe , Pevet Paul
Published: February 2007

Abstract: The European hedgehog (Erinaceus europaeus L.) is a hibernating mammal and seasonal breeder in which numerous circadian and circannual rhythms are entrained and synchronized by photoperiod. The present study was undertaken in order to establish the involvement of the pineal gland in transducing the photoperiodic message in this species. Pineal melatonin concentrations were determined by radioimmunoassay in female hedgehogs kept under natural climatic conditions and killed during the light:dark (L:D) cycle in spring and autumn, after the interruption of darkness by a 45 min light pulse, and after bilateral superior cervical ganglionectomy (SCGx). Absolute melatonin concentrations were low (< 100 pg/pineal) in the pineal gland. Under natural climatic conditions, in spring and in autumn, pineal melatonin concentrations exhibited a marked diurnal rhythmicity, with very low levels in the day (1200: < 10 pg/pineal) and high levels during the night (2200: 71.9 ± 18.6 pg/pineal; 0200: 42.5 ± 15.6 pg/pineal). The 45 min light pulse during darkness depressed rapidly and significantly the melatonin content (dark + light [D + L]: < 10 pg/pineal), but a subsequent return to darkness restored high melatonin content after approximately 2 h (D + L + D: 65.4 ± 20.2 pg/pineal). After bilateral SCGx, melatonin concentrations were reduced and no increase during night could be observed, either in animals sacrificed 42 days after SCGx or in animals killed 2 years after SCGx. In the hedgehog, as in other mammals, pineal melatonin concentrations are related to the light:dark cycle. Such data indicate that during the year, in this species, the effects of light on seasonal endocrine rhythms may be mediated by the pineal gland.
Localization and quantification of high‐affinity melatonin binding sites in Rana pipiens retina
Authors: Wiechmann Allan F. , Wirsig‐Wiechmann Celeste R.
Published: February 2007

Abstract: Melatonin binding was localized to the inner plexiform layer (IPL) of the frog retina by in vitro autoradiography, using 2‐125I‐melatonin as the radioligand. Radioreceptor binding assays of frog retinal homogehate demonstrated saturable melatonin binding. Scatchard analysis revealed a single population of binding sites with an apparent dissociation constant (Kd) of 125 pM, with a Bmax of 0.138 fmoles/mg of protein. These results suggest that high‐affinity melatonin binding sites are present in the IPL of the frog retina, which may reflect the presence of melatonin receptors in this synaptic layer.
Adenosine 5′‐monophosphate enhances the dark and isoproterenol‐induced rise in rat pineal N‐acetyltransferase activity
Authors: Olivieri Gianfranco , Daya Santy
Published: February 2007

Abstract: Exposure of rats to light during darkness or blockade of the pineal β‐adrenoceptor in stimulated pineal glands results in a rapid fall in pineal N‐acetyltransferase (NAT) activity. Maintenance of a high level of NAT activity requires continuous stimulation of the pineal β‐adrenoceptors. It is not known what factors in the pinealocyte are responsible for this rapid inactivation of NAT activity. In the present study we have attempted to investigate a possible regulatory role of 5′‐AMP on pineal NAT activity. The results show that 5′‐AMP further enhances dark‐induced as well as isoproterenol‐induced NAT activity by approximately 3‐fold but does not alter unstimulated daytime NAT activity. Theophylline, an inhibitor of 5′‐AMP synthesis, when administered early in the dark phase, caused a rise in pineal cAMP with a concomitant fall in pineal NAT activity. These findings indicate that 5′‐AMP could play a role in the activation of pineal NAT. The possibility that the rapid inactivation of NAT is due to a rapid removal of 5′‐AMP by, for example, phosphorylation, remains to be investigated.
Components of the melatonin message in the response to photoperiod of the tammar wallaby (Macropus eugenii)
Authors: Tyndale‐Biscoe C.H. , Hinds L.A.
Published: February 2007

Abstract: Female tammars experiencing long‐day photoperiod (LD 15:9) are in a reproductive state termed seasonal quiescence. After a change to LD 12:12, a sequence of endocrine events, dependent on a melatonin message being interpreted during the next 3 days, leads to the disappearance of a morning pulse of prolactin on day 4, and to reactivation of the quiescent corpus luteum by day 8. Elements of the message were investigated in three experiments. In experiment 1, tammars on LD 15:9 were injected with melatonin 2.5 hr before lights out on 0–5 successive days. All those receiving four or five daily injections, and six often receiving two or three injections, reactivated, n experiment 2, tammars on LD 15:9 were injected with melatonin or oil on 5 consecutive days to achieve a lengthening of the period of elevated melatonin from 9.0 hr to 9.5 hr, 10 hr, 10.5 hr, and 11.5 hr respectively. One of five tammars experiencing 10 hr and seven of ten experiencing the longer periods reactivated. In experiment 3, tammars on LD18:6 received melatonin 6 hr, 6 + 3 hr or 3 hr before lights out for ten successive days. Between injections the melatonin concentrations returned to basal levels. The treatments thus provided a skeletal increase in the profile of melatonin from 6 to 9 hr or 6 to 12 hr. All those treated at 6 + 3 hr reactivated and three of five treated at 6 hr only reactivated. We conclude that the tammar stores information about the change in the maximum duration of elevated melatonin experienced each night and, after three successive periods in which the duration is greater than 10.5 hr, it reactivates. Since reactivation cannot occur until completion of the third dark phase, the processing center must be active during the fourth day, prior to the abolition of the prolactin peak.
Diurnal variations of urinary 6‐sulphatoxymelatonin in male intact or ganglionectomized mink
Authors: Maurel Daniel , Mas Nicole , Roch Gisèle , Boissin Jean , Arendt Joséphine
Published: February 2007

Abstract: The existence of the major urinary metabolite of melatonin, 6‐sulphatoxymelatonin (aMT6s), was validated for mink and the 24 hr urinary excretion pattern was determined in intact and superior cervical ganglionectomized animals under different photoperiodic conditions. Within‐and between‐assay variations, parallelism between serially mid‐night pooled urine dilutions and standard curves in aMT6s free urine of mink at 1:125 dilution and recovery of aMT6s in mid‐day pooled urine at 1:125 dilution provided a good validation for the mink urinary a MT6s assay. In natural photoperiods (January, LD 9:15; April, LD 13:11) the diurnal rhythm was characterized by low aMT6s values during the day and high values at night. There were no differences in the nocturnal values measured under long‐ (April, 4.11 ± 0.40 ng/hr) or short‐day (January, 4.74 ± 0.36 ng/hr) conditions. In an experimental long photoperiod (LD 15:9), the same result was obtained on the 24 hr rhythm in intact animals, but in ganglionectomized mink the nocturnal rise in aMT6s was abolished and the nocturnal values were always low (0.88 ± 0.09 ng/hr). Our results agree with those obtained in other species concerning plasma melatonin rhythm and urinary aMT6s excretion; we thus conclude that this is an effective assay for measuring pineal activity in mink.
An oral melatonin replacement regimen that re‐establishes the normal circadian levels of urinary 6‐sulphatoxymelatonin in functionally pinealectomized rats
Authors: John T. Mathew , Brown M. Catherine , Brown Gregory M.
Published: February 2007

Abstract: Wistar rats maintained on a 12‐hr daily photoperiod (LD 12:12 cycle) exhibited a diurnal rhythm in urinary 6‐sulphatoxymelatonin (aMT6s) concentrations with peak levels in the scotophase. Light‐induced functional pinealectomy (FPX) abolished the nocturnal rise in aMT6s, lowering it to photophase levels. The objective of the study was to formulate an oral melatonin replacement regimen that would restore a normal rhythmic output of urinary aMT6s in functionally pinealectomised rats. Three regimens of sequential doses of melatonin were tested. Of these, the regimen with melatonin concentrations of 4 ng, 12 ng, 65 ng, and 4 ng per ml of drinking water given to rats during the 1st, 2nd, 3rd, and 4th 3‐hr periods, respectively, of the 12‐hr FPX phase, was found to generate a urinary aMT6s level that closely resembled the natural level and rhythm exhibited under an LD 12:12 cycle. This dose is considered appropriate to restore certain melatonin‐mediated physiological functions in Wistar rats subjected to FPX.
Immunohistochemical study of the pineal glial cells in the postnatal development of the rat pineal gland
Authors: Borregón Antonio , Boya Jesús , Calvo Jose Luis , López‐Muñoz Francisco
Published: February 2007

Abstract: The developmental expression of the glial antigens, vimentin (VIM), glial fibrillary acidic protein (GFAP), and S‐100 protein is described in the rat pineal gland from the first postnatal day to adulthood. Thick VIM immunopositive cell cords forming a network throughout the pineal gland were observed from the first postnatal days. These cords progressively disappeared during the first postnatal month as their cells dispersed into the pineal parenchyma. From 20 to 25 postnatal days, pineal glial cells appeared as isolated star‐shaped VIM immunopositive cells. Immunostaining for GFAP and S‐100 protein showed a similar developmental expression pattern. Both antigens appeared later than VIM (15–20 postnatal days) and were restricted to the pineal glial cells located in the proximal third of the gland, close to the pineal stalk.
Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy
Authors: Lewiński A. , Szymczykiewicz P. , Sewerynek E. , Wajs E.
Published: February 2007

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham‐PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross‐sectional area, cross‐sectional area of the granulosa layer of all the Graafian follicles and the cross‐sectional areas of the corpora lutea, visible on the ovarian cross‐section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham‐PX, melatonin effects on these two groups may differ.
A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters
Authors: Hong Seung M. , Rollag Mark D. , Ramirez Julie , Stetson Milton H.
Published: February 2007

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near‐basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three‐way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three‐way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.
Inhibitory effect of melatonin on platelet activation induced by collagen and arachidonic acid
Authors: Kornblihtt Laura I. , Finocchiaro Liliana , Molinas Felisa C.
Published: February 2007

Abstract: Melatonin, an indolamine synthesized in the pineal gland, is known to have antiprostanoid activity. The inhibition of platelet aggregation induced by melatonin has been proposed to take place through the cyclooxygenase pathway. In the present study, we found that melatonin has a marked inhibitory effect on collagen, arachidonic acid (AA), adenosine diphosphate (ADP), epinephrine, and A23187‐induced aggregation in platelet‐rich plasma. On the other hand, using metrizamide‐filtered platelets resuspended in Tyrode's buffer, melatonin fails to suppress AA‐induced platelet aggregation and 14C‐5‐HT release. Under the same conditions, melatonin inhibits collagen‐induced platelet activation; however, the addition of threshold doses of AA (0.3 mM) abrogates this effect. These studies suggest that melatonin also inhibits platelet function at a stage preceding the cyclooxygenase‐dependent pathway.
Melatonin and sleep in humans
Authors: Dawson Drew , Encel Nicola
Published: February 2007

Abstract: Early studies on the physiological effects of melatonin typically reported hypnotic ‘side‐effects’. Later studies, specifically addressing this action, failed to reliably replicate hypnotic effects using standard polysomnography. This difference may be related to differences in the basic physiological action of melatonin compared with more conventional hypnotics. It is suggested that melatonin exerts a hypnotic effect through thermoregulatory mechanisms. By lowering core body temperature, melatonin reduces arousal and increases sleep‐propensity. Thus, in humans, one role of melatonin is to transduce the light‐dark cycle and define a window‐of‐opportunity in which sleep‐propensity is enhanced. As such, melatonin is likely to be an effective hypnotic agent for sleep disruption associated with elevated temperature due to low circulating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep disorders related to the inappropriate timing of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production (e.g., β‐blockers and benzodiazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square‐wave pulse of melatonin at physiological levels for 8–10 hr duration.
Effect of pinealectomy and plane of nutrition on wool growth in Merino sheep
Authors: Foldes Andrew , Maxwell Colin A.
Published: February 2007

Abstract: The effects of surgical pinealectomy and plane of nutrition on wool growth and plasma prolactin concentrations in young Merino wethers were investigated. In young pinealectomized wethers maintained at a low live weight under conditions of minimal stress, the decline of conditioned clean wool production on midside patches was slowed when compared to pineal‐intact controls. This difference appeared to be due in part to the observed greater secondary wool follicle density in the pinealectomized wethers; mean fiber diameter was affected to a smaller extent, while staple length growth rate was not significantly altered. Circulating prolactin profiles showed a seasonal variation (high in summer, low in winter) in both pinealectomized and control wethers. There was no difference in wool production between pinealectomized and control wethers when the diet of the same wethers was subsequently supplemented with formaldehyde‐treated cottonseed meal. While the role of melatonin in the regulation of wool growth remains to be determined, it is suggested that the hormone may have a transient effect on wool production in young wethers under conditions of limited nutrition, but not at higher nutritional levels, and that melatonin may be involved in partitioning of nutrients to the wool follicle.