bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of Synaptic Ribbons in Pineal Photoreceptors Under Normal and Experimental Lighting Conditions
Authors: McNulty John A.
Published: February 2007

The size of synaptic ribbons (SR) in photoreceptor cells of the goldfish pineal organ was quantified over 24‐h light:dark cycles of long (16:8) and short (10:14) photoperiods during summer and winter months, respectively. The amplitude of both rhythms was similar with peak values occurring toward the latter part of the photophase or early dark. When fish were entrained to the long photoperiod and exposed to continual light, SR size continued to increase during the expected dark time. The effect of extending the photoperiod into the expected dark time was diminished when fish were entrained to a short photoperiod and presented with 6 h of darkness at the end of the 24‐h period. The size increase in response to environmental lighting is believed to reflect a greater demand for either vesicle attachment sites or neurotransmitter storage sites since vesicles (neurotransmitter) have been hypothesized to accumulate in the synaptic pedicles during inhibition by light. From a comparative standpoint it is noteworthy that synaptic ribbons (vesicle‐crowned rods) in mammals react in a similar manner to both normal and experimental lighting conditions.
In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
Authors: Lowenstein Pedro R. , Solveyra César González , Cardinali Daniel P.
Published: February 2007

As a part of a study aiming to characterize the physiological and pharmacological significance of the high affinity pineal benzodiazepine (BZP) binding sites reported previously, we examined the uptake of the BZP derivative 3H‐flunitrazepam (FNZP) by rat pineal glands in vitro. At 37 °C, 3H‐radioactivity was taken up by tissue up to a pineal/medium concentration of about 12, while at 0 °C the uptake amounted to only one‐third that at 37 °C. Reciprocal of uptake analyzed by Lineweaver‐Burk plots indicated apparent Km's of 1.74 and 1.45 μM, and Vmax's of 1.32 and 1.04 pmol per min per mg tissue, for control and superior cervical ganglionectomized rats, respectively, suggesting that the neural compartment does not participate significantly in 3H‐FNZP uptake. Cerebral cortex explants of similar size and weight as the pineal ones took up 3H‐FNZP to a maximum tissue/ medium concentration of about 2. Neither pineal nor cerebral cortex 3H‐radioactivity uptake exhibited significant changes as a function of time of day. A number of agents, including several BZP analogues, cocaine, desipramine, melatonin, fluoxetine, nomifensine, and dipiridamol, as well as changes in the ionic environment or metabolic inhibitors, did not affect 3H‐FNZP uptake significantly. Other tissues, such as liver, muscle, kidney, adrenal gland, or anterior pituitary, took up 3H‐radioactivity to tissue concentrations slightly lower than those of the cerebral cortex, suggesting that drug liposolubility accounted only to a limited extent for the high in vitro uptake detected in incubated pineals.
Temporal Effects of Norepinephrine on Pineal Serotonin In Vitro
Authors: Walker R. F. , Sparks D. L. , Slevin J. , Rush M. E.
Published: February 2007

The purpose of this study was to examine the temporal effects of norepinephrine (NE) stimulation on pineal serotonin (5HT) in vitro. Rat pineal glands were individually incubated in nutrient media for 6 h. After a 2‐h preincubation, the glands were exposed to tryptophan (TRYP) or TRYP + norepinephrine (10−4 M each) for 4 additional h. Media and pineals were then analyzed for 5HT and 5HIAA content. Initial exposure to TRYP increased 5HT levels in the media. Norepinephrine increased media 5HT concentrations further and also caused 5HIAA levels to rise significantly. These findings suggest that 5HT secretion and/or oxidation is an early response to stimulation of the pineal gland by NE. Following prolonged NE exposure, media 5HT declined to control values while 5HIAA remained high. Similarly, intrapineal levels of 5HT fell after prolonged stimulation with NE. Thus, pineal responses to initial and continued stimulation with NE are differentiable as early and late effects upon 5HT. Early effects may include secretion and/or oxidation of 5HT followed later by utilization of 5HT in N‐acetylation pathways such as that leading to melatonin synthesis. The finding that 5HT is secreted in response to NE suggests that the indoleamine may be a hormone of the pineal gland. Based upon its known influence on physiologic rhythms, daily secretion of 5HT from the pineal may be an important part of the gland's time‐keeping function.
Neuropharmacological Modification of Central Catecholamines: Effects on Pinealectomy‐Induced Convulsions
Authors: Stockmeier Craig A. , Blask David E.
Published: February 2007

Removal of the pineal gland produces stereotyped tonic convulsions in parathyroidectomized rats. Inasmuch as central levels of norepinephrine (NE) are decreased in these animals, the purpose of this study was to investigate the effects of alterations in central catecholamine function on convulsions produced by pinealectomy in parathyroidectomized rats. The treatment of rats with α‐methyl‐p‐tyrosine or FLA‐63 produced large reductions in forebrain levels of both NE and dopamine or NE alone, respectively, which were not associated with facilitation of convulsions. However, the incidence of convulsions was increased by FLA‐63 in rats pretreated with the catecholamine precursor L‐dihydroxyphenylalanine. Reserpine, a monoamine depleter, had no effect on either the incidence or severity of convulsions. An acute injection of desipramine, an inhibitor of the reuptake of NE, however, significantly lowered the incidence of convulsions. Timolol, a β‐adrenergic receptor antagonist, reduced, in a dose‐dependent manner, the average latency to onset of convulsions and increased the average number of convulsions each rat experienced. Clonidine, an α2‐adrenergic agonist, did not significantly alter convulsions. Thus presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy‐induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect. Further evidence suggesting a role for NE in modulating these convulsions is provided by the proconvulsant effect of blocking central β‐adrenergic receptors.
Seasonal Changes in the Pineal Organ of Control and Gonadectomized Fish (Mystus vittatus [Bloch])
Authors: Kumar Rajendra , Sriwastwa Vishnu Mohan Sahai
Published: February 2007

The surface area and luminal structures of the pineal sac were studied during the prespawning, spawning, and postspawning phases of control and gonadectomized fish, Mystus vittatus, throughout the year. From the later half of prespawning to the first half of postspawning phases the values for the surface area were lower in the gonadectomized group whereas from the later half of the postspawning to the first half of prespawning phases the values were higher than in the control group. The acidophilic cell bodies were visible in the first half of prespawning and at the end of spawning phases as well as during the postspawning phase. In the control group sulfated acid mucopolysaccharides and mucoid basophils with gamma substances were faintly stained during the early months of the reproductive cycle in contrast to the experimental group; but in the later months these substances were strongly stained in both groups except in the gonadectomized group at the end of postspawning phase. The pineal lumen was narrow during the pre‐ and postspawning phases and wider in the spawning phase of the gonadectomized group in comparison to control; this may be related to the flow of cerebrospinal fluid. Thus, the morphohistochemical changes in the pineal organ of fish were evident in both groups during the prespawning, spawning, and postspawning phases.
Effects of Melatonin and 5‐Methoxytryptamine on Sleep‐Wake Patterns in the Male Rat
Authors: Mirmiran Majid , Pévet Paul
Published: February 2007

Melatonin and 5‐methoxytryptamine were administered continuously over a period of 1–3 months to adult male rats by means of subcutaneously implanted silastic capsules containing one or the other of these pineal hormones. Polygraphic recordings during several weeks following hormonal application showed an increase in the amount of time spent in both quier and rapid eye movement sleep, during the light as well as the dark period; however, diurnal sleep‐wake rhythmicity was not affected by either treatment. We conclude that pineal hormones have sleep‐promoting effects, but that their correlation with the lightdark cycle does not imply that they are causal factors in generating diurnal rhythms of sleep and wakefulness.
Effects of Long and Short Photoperiod on the Ultrastructure of Pinealocytes of the Cotton Rat (Sigmodon hispidus)
Authors: Karasek Michal , Matthews Susan A. , King Thomas S. , Reiter Russel J.
Published: February 2007

The ultrastructure of the pinealocytes of wild‐captured cotton rats (Sigmodon hispidus) housed in either long or short photoperiod was examined. Quantitative comparison of selected pinealocyte organelles revealed larger relative volumes of mitochondria, granular endoplasmic reticulum and ribosomes, Golgi apparatus, and inclusion bodies, as well as a higher number of dense‐core vesicles in the animals kept in short photoperiod (LD 8:16) as compared to those in animals kept in long photoperiod (LD 16:8). These observations suggest that restricting the amount of light to which animals are exposed activates pinealocytes of the cotton rat.
Rats on 22.5‐Hr Light:Dark Cycles Have Vaginal Opening Earlier Than Rats on 26‐Hr Light:Dark Cycles
Authors: Lehrer Steven
Published: February 2007

Rats on 22.5‐hr light:dark cycles had vaginal opening significantly earlier than rats on 26‐hr light:dark cycles. This finding might explain the early menarche in blind girls: Their circadian rhythms, like those of rats on 22.5‐hr cycles, might be more rapid than normal. Thus a set number of cycles can occur in a shorter time than usual, allowing puberty to take place early.
Human Melatonin Production Decreases With Age
Authors: Sack Robert L. , Lewy Alfred J. , Erb Danielle L. , Vollmer William M. , Singer Clifford M.
Published: February 2007

The purpose of this study was to investigate the effects of time of year and demographic variables on the amplitude of melatonin production in normal human subjects. Melatonin production was estimated by measuring the overnight excretion of its major urinary metabolite, 6‐hydroxymelatonin. Urine was collected on three consecutive nights in the summer from a sample of 60 normal subjects balanced for sex and age. The collections were repeated in a subgroup during the winter. Melatonin production clearly declined with age but was not influenced by other demographic variables or by season of the year.
Influence of the Pineal Gland and Melatonin on Blood Flow and Evaporative Water Loss During Heat Stress in Rats
Authors: Harlow Henry J.
Published: February 2007

Plasma melatonin levels of laboratory rats were elevated both during acute heat exposure (43°C for 40 min) and chronic exposure (33°C for 17 days) suggesting a possible correlation between melatonin and thermoregulatory mechanisms. Pinealectomy reduced the nighttime elevation in oxygen consumption and evaporative water loss. In addition, pinealectomized animals exhibited a significantly lower cutaneous evaporative water loss both at night and during the day when exposed to an acute heat exposure of 38°C for 45 min. Pinealectomy elevated the blood pressure over the control group whereas melatonin infusion depressed the blood pressure without altering the cardiac output. This relationship implies an action by melatonin on the peripheral vasculature. In support of this conclusion, melatonin pretreatment tended to dampen the vasopressive effect of infused norepinephrine. These data, therefore, suggest a role of the pineal gland and melatonin in thermoregulation through an influence on the cardiovascular system and evaporative water loss.
Depression in Rat Pineal N‐Acetyltransferase Activity and Melatonin Content Produced by a Hind Leg Saline Injection is Time and Darkness Dependent
Authors: Troiani Maureen E. , Oaknin Sol , Reiter Russel J. , Vaughan Mary K. , Cozzi Bruno
Published: February 2007

It has recently been shown that a 1.5‐ml subcutaneous saline injection into the dorsal aspect of the hind limb induces a dramatic and rapid fall in N‐acetyltransferase activity and melatonin content of the rat pineal gland at night. Since many studies have shown the opposite response to stress during the day, the first experiment was undertaken to test whether the timing of the saline injection at night influences the response of the pineal gland. In the present studies, rats were kept under light:dark (LD) cycles of 14:10 with lights out daily at 2000 h. Groups of rats were then given a saline injection at one of the following times: 2315, 0015, 0115, 0215, or 0315. Early in the dark phase (2315 and 0015) the saline injection depressed both the N‐acetyltransferase (NAT) activity and the melatonin content of the pineal. As the animals were treated later in the dark period, the response became more blunted and, finally, disappeared. In the second experiment, animals that were kept in light during the usual dark period showed no pineal response when subjected to a hind leg injection of saline at either 2315 or 0315. Additionally, no response was seen in the two pineal parameters when rats had darkness onset delayed by 4 h (to 2400) and were then treated with saline at 0410. The results of these studies indicate that the pineal response to saline injection is time dependent. Also, if the nighttime rise in melatonin is suppressed by light exposure, a saline injection has no further inhibitory effect on pineal NAT activity or melatonin levels.
Failure of Melatonin To Inhibit the Mitotic Activity of Regenerating Adrenal Cortex in Rats
Authors: Karasek Michal , Zieleniewski Jerzy , Nowakowska‐Jankiewicz Barbara
Published: February 2007

Although there is little evidence that melatonin may have a direct antimitotic effect on various cells, it has been shown that this pineal compound may influence the cell proliferation of either normal or neoplastic cells. Therefore, the influence of melatonin on the mitotic activity of regenerating adrenal cortex of rats was studied. The mitotic activity was counted in the adrenal cortex or rats on days 2, 7, and 12 following enucleation of the adrenals. Melatonin did not influence the mitotic activity of regenerating adrenal cortex in the rat.
Annulate Lamellae in the Pineal Organ of a Tinamid Bird
Authors: Redins Carlos Alberto , Machado Angelo Barbosa Monteiro
Published: February 2007

This study reports the occurrence of annulate lamellae in the rudimentary photoreceptor cells of the pineal organ of a tinamid bird Crypturellus parvirostris. The annulate lamellae observed in these cells are located in the cell body and are comprised of 1 to 8 parallel lamellae, symmetrically aligned and regularly spaced. Each lamella consists of pairs of parallel membranes interrupted by regularly spaced pores or annuli. These observations are discussed and compared with the structure and distribution of these organelles referred in the literature.
Effect of Melatonin on the Human Electrocardiogram and Simple Reaction Time Responses
Authors: Wynn Vernon Thomas , Arendt Josephine
Published: February 2007

It has been suggested that melatonin may have therapeutic potential for alleviating jet lag. In an attempt to define further the effects of low pharmacological doses of melatonin on the human body, 5 mg of melatonin was given orally to one subject in a blind experiment. The electrocardiogram (ECG) was recorded together with simple reaction time (SRT) responses over a 5‐h period after taking melatonin. The main part of the project was carried out under artificial domestic lighting conditions and involved ten evening sessions.

Microprocessor analysis of the ECG of one subject clearly showed that melatonin had the effect of lengthening the RR interval, that between the peak of the P wave and the onset of the R wave, and the interval between the onset of the R wave and the peak of the T wave. A model to explain the cubic curve, which was fitted by regression analysis to the data, implies that the natural evening increase in melatonin may also increase these intervals. The results suggest that melatonin may affect both the phase and the amplitude of the observed ECG phenomenon.

Analysis of more than 40,000 SRT responses to both visual and auditory stimuli implied that these responses might also be lengthened by melatonin. Frequency histograms of the responses and observations on premature and missed responses were not able to reproduce the results of other workers who found that higher doses (240 mg) of melatonin decreased the number of incorrect responses to simple reaction time tasks.
Effects of Prior Exposure to Prolonged Continuous Light on the Pattern of Melatonin Secretion in Sheep Held Under Continuous Darkness
Authors: Shaw Paul F. , Kennaway David J. , Seamark Robert F.
Published: February 2007

To gain insight into the nature of the neural centre regulating melatonin production by the pineal gland we have measured hourly changes in plasma melatonin in 16 ewes held for 42–56 h under continuous darkness following a 28‐day period of exposure to continuous light. Plasma melatonin was undetectable while animals were in constant light but increased to normal night time levels (120–2,200 pmol/litre) within 10 min of the onset of darkness in 14 out of the 16 ewes regardless of whether this occurred at 1200 h (group 1) or 2400 h (group 2). In four ewes melatonin secretion was maintained for approximately 36 h, indicating that the pineal gland remained responsive to a static stimulatory signal presumably emanating from the supra chiasmatic nucleus. In all ewes, melatonin secretion ceased at approximately 12 and or 36 h after the onset of darkness and did not require a separate zeitgeber. Although the increase and the decline of plasma melatonin levels were synchronized within groups 1 and 2, there were sufficient differences in the pattern of melatonin secretion between the groups to suggest that the regulatory mechanism had an intrinsic component. A hypothesis involving a diurnal change in sensitivity to circulating melatonin is advanced to explain the observed differences in the synchrony of melatonin secretion and the prolonged episodes of melatonin secretion.
Inhibition of Pineal Type‐II 5′‐Deiodinase Does Not Affect the Nocturnal Increase of N‐Acetyltransferase Activity and Melatonin Content in Either Euthyroid or Thyroidectomized Rats
Authors: Guerrero Juan M. , Puig‐Domingo Manuel , Santana Celsa , Menendez‐Pelaez Armando , Reiter Russel J.
Published: February 2007

The presence of type‐II thyroxine 5′‐deiodinase (5′‐D) activity in rat pineal gland has been previously described. In the present paper, 5′‐D activity, N‐acetyltransferase (NAT) activity, and melatonin content were measured in the same rat pineal. Each of these constituents exhibits a nocturnal increase with peak values at 0100 h for melatonin (1.20 ± 0.12 ng/gland) and at 0300 h for both 5′‐D (39.5 ± 11.9 fmol/gland/h) and NAT (8.38 ± 1.04 nmol/gland/h) activities. In vivo treatment with iopanoic acid (IOP) completely prevented the nocturnal increase in 5′‐D activity (14.1 ± 2.6 fml/gland/h at 0300 h) with no modification in either the NAT activity or melatonin content. Thyroidectomy greatly enhanced the 5′‐D activity during the dark period (102.9 ± 10.2 vs. 31.6 ± 4.2 fmol/gland/h), reaching a peak at 0200 h; thyroidectomy, however, did not affect daytime pineal 5′‐D activity (3.11 ± 0.78 vs. 2.5 + 0.92 fmol/gland/h). Treatment of rats with IOP acid completely inhibited the pineal 5′‐D activity in both control (7.86 ± 0.88 fmol/gland/h) and thyroidectomized animals (2.24 ± 1.10 fmol/gland/h) with no change in the melatonin content of the gland (1.21 ± 0.32 vs. 0.99 ± 0.18 ng/gland).
Histochemical Localization of Cyclic 3′, 5′‐ AMP Phosphodiesterase in Rat Pineal Gland
Authors: Chons Margarita Heredia , Corazza Juan Pablo , Pellegrino de Iraldi Amanda
Published: February 2007

Female Wistar rats maintained in a light: dark 12: 12 photoperiod cycle were used to investigate the histochemical localization of the cAMP phosphodiesterase activity in the pineal gland of rats killed in the light period or in the dark period of the diurnal lighting regimen. Enzyme activity was identified along the plasma membrane of pinealocytes. The distribution of phosphodiesterase activity for cyclic guanosine monophosphate was similar to that found for cyclic adenosine monophosphate, suggesting that the same enzyme hydrolyzes both nucleotides. In the theophylline control, the reaction product along the plasma membrane of pinealocytes disappeared almost totally. In control sections without substrate, no reaction product was found. The animals decapitated in the dark period of the diurnal cycle showed a distribution of phosphodiesterase activity similar to that found in animals killed in the light period.
Effect of Methoxyindole Administration on Plasma Cation Levels in the Rat
Authors: Morton Dougal J.
Published: February 2007

Administration of methoxyindoles to rats in both the morning and the afternoon caused significant changes in circulating plasma cation levels. All the methoxyindoles except melatonin were without effect at doses below 100 μg/kg; the observed changes caused by doses of 100 μg/kg can, therefore, probably be best described as pharmacological rather than having physiological significance. Melatonin at all doses tested (25, 50, and 100 μg/kg) led to a decrease in plasma magnesium levels 3 h after administration in the morning, and this finding is discussed in the light of a possible feedback mechanism between melatonin and circulating magnesium. Melatonin administration in the afternoon was without effect on magnesium levels. Zinc levels were also decreased significantly 3 h after a morning dose of melatonin (50 and 100 μg/kg), and the possible functional significance of this observation is discussed. Most of the observed effects can be considered nonspecific and pharmacological, and further work is needed to fully elucidate the involvement, if any, of the pineal gland in regulation of cations.
Rhythm Development in Pineal and Circulating Serotonin, N‐Acetylserotonin, and Melatonin in Syrian Hamsters
Authors: Sato Tetsuji , Attanasio Andrea , Wake Kenjiro , Gupta Derek
Published: February 2007

The ontogeny of diurnal rhythm patterns in the pineal and serum levels of melatonin, serotonin, and N‐acetylserotonin was studied in Syrian hamsters (Mesocricetus auratus) from birth to adulthood. The pineal and blood specimens were collected at 1100 h and 0200 h, and the compounds were measured by radioimmunoassay (RIA) procedures. Pineal melatonin and serotonin did not show any circadian rhythm at day 5 of postnatal age. At this age N‐acetylserotonin was undetectable in the light phase but became manifest at night. By 10 days of age pineal serotonin registered an established rhythm pattern, with a higher level during the day. The occurrence of circadian rhythm in pineal melatonin was delayed and manifested first at 25 days of age. At this age, the first detectable daytime level of N‐acetylserotonin also occurred. Circadian rhythm in serum melatonin was also established at this age. The serum serotonin did not evince any rhythm pattern throughout the observation period, except at day 17 of postnatal age. The massive concentration of daytime serotonin in the pineal was not reflected in the circulatory system. For serum N‐acetylserotonin there was no discernable day‐night rhythm in all age groups, except at 25 days of age. The results show that the timing of the appearance of various compounds in the neonatal pineal is variable; the release of the substances does not always reflect their synthesis; the ontogenesis of circadian rhythm is a part of the maturational process; and 25 days of age is a rather critical time in development.
Extraretinal Mechanisms Mediate Light‐Induced Changes in Neonatal Rat Pineal Gland N‐Acetyltransferase Activity
Authors: Torres German , Lytle Loy D.
Published: February 2007

Nocturnal light‐induced changes in pineal gland N‐acetyltransferase activity were investigated in intact or enucleated 4‐, 6‐, or 8‐day‐old maternally isolated rats maintained at different ambient temperatures. Nighttime enzyme activity was increased markedly in rats maintained in 23°C compared to 35°C environments. Four hours of nocturnal light significantly reduced N‐acetyltransferase activity in intact rats at all ages studied when the animals were maintained at 35°C. Shorter duration (1 min) nocturnal light reduced N‐acetyltransferase activity in intact rats 6 days of age. However, the enzyme activity suppression observed after the 4 hr of nocturnal light was still present in 4‐day‐old rats (but not older animals) even when the younger animals had been made blind by bilateral orbital enucleation. Taken together, these data suggest that an extraretinal mechanism may mediate light‐induced changes in some aspects of pineal gland indoleamine biochemistry in newborn rats.
Increased FSH Levels Precede Short Photoperiod‐Induced Anestrus in Intact and Unilaterally Ovariectomized LSH/SsLak Hamsters
Authors: Hauser Ursula E. , Benson Bryant
Published: February 2007

Anestrus brought about after 2–4 weeks of short photoperiod (SP) exposure in LSH/SsLak hamsters is preceded by impaired follicular development. Since the latter is critically dependent on adequate FSH levels, this study tested the hypothesis that SP might alter baseline or compensatory FSH levels prior to the onset of anestrus. Regularly cycling females in 14L:10D (LP) were transferred to SP (8L: 16D). Between 0800 and 0900 h on days 20 through 24 of SP exposure, half of the animals in diestrus II were unilaterally ovariectomized (UO), and the remaining animals were sham‐operated (Sham‐UO). Seven hours after surgery, blood samples were taken via cardiac puncture. All animals were killed the following morning at 0900 h. Uterine weights were significantly reduced in SP‐exposed hamsters, yet the compensatory increase in FSH following unilateral ovariectomy was not affected; a tendency for higher levels was noted. On proestrus, serum and pituitary FSH levels of SP‐exposed Sham‐UO animals were significantly elevated over similarly treated LP‐exposed hamsters. Interestingly, in animals with severe follicular impairment, the highest FSH levels correlated with the lowest uterine weights. The data suggest that SP exposure does not impair compensatory FSH release or the ability of the ovaries to respond to UO. SP‐induced elevations in FSH levels may result from reduced follicular secretion and reduced inhibin and/or estrogen levels.
Antigonadal Activity of the Melatonin Analogs 2‐Iodomelatonin and 2‐Chloromelatonin in the Juvenile Djungarian Hamster, Phodopus sungorus campbetti
Authors: Sugden David
Published: February 2007

The antigonadal effects of daily (20 (μg, s.c.) injection of melatonin and two analogs, 2‐iodomelatonin and 2‐chloromelatonin, were compared in juvenile Djungarian hamsters housed under long photoperiod (L:D 16:8). Melatonin, 2‐iodomelatonin, and 2‐chloromelatonin injected 3h before lights off for 16 days (17–34 days of age) significantly inhibited testis growth compared to vehicle‐injected hamsters. In addition, melatonin and both analogs significantly reduced body weight gain. These 2‐substituted analogs appear to be melatonin agonists with a potency in vivo similar to the parent compound, melatonin.
Light Suppression of Melatonin in the Squirrel Monkey (Saimiri sciureus)
Authors: Hoban Tana M. , Lewy Alfred. J. , Fuller Charles A.
Published: February 2007

This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12: 12 light‐dark cycle (LD 12: 12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 ± 18.9 pg/ml) were significantly higher than at 02:00 (57.21 ± 7.7 pg/ml; Student's t = 2.859; P≤ 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 ± 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals.
Vasoactive Intestinal Peptide‐Like Immunoreactive Nerve Fibers in the Pineal Gland of the Sheep
Authors: Cozzi Bruno , Mikkelsen Jens D. , Merati Danila , Capsoni Simona , Møller Morten
Published: February 2007

Vasoactive intestinal peptide (VIP)‐like immunoreactive nerve fibers were demonstrated by peroxidase antiperoxidase (PAP) inmmunohistochemistry to be distributed throughout the entire pineal gland of the sheep. VIP‐containing fibers were observed along the blood vessels, penetrating into the gland from the pial capsule and also in the capsule itself. Some fibers left the perivascular position and entered the pineal parenchyma, where they were located among pinealocytes. This suggested that the VIPergic fibers might influence both pinealocytes and blood vessels of the gland. The location of VIP‐containing fibers in the capsule of the pineal gland indicates that the fibers originate from perikarya located in a peripheral ganglion.
Comparison of the Rat Pinealocyte Ultrastructure With Melatonin Concentrations During Daytime and at Night
Authors: Karasek M. , Stankov B. , Lucini V. , Scaglione F. , Esposti G. , Mariani M. , Fraschini F.
Published: February 2007

The aim of this study was to investigate the ultrastructure of rat pinealocyte during daytime (1600 h) and at night (0100 h) and to compare these observations with serum melatonin levels in the same animals. In addition, pineal melatonin concentrations were determined in other animals. Both serum and pineal melatonin concentrations were significantly higher at night than during daytime (34 and 21 times, respectively). Sizes of pinealocytes, their nuclei, and nucleoli, as well as cross‐sectional areas of mitochondria and granular endoplasmic reticulum were also higher at night than during daytime, whereas areas of lysosomes, Golgi apparatus, and vacuoles containing flocculent material did not differ at the time points studied. In contrast, the number of dense‐core vesicles was higher during daytime. The results of the present study show that morphological patterns of higher metabolic activity of the rat pinealocyte at night when compared to those during daytime correlate with melatonin concentrations.
GABA‐immunoreactive intrinsic and ‐immunonegative secondary neurons in the cat pineal organ
Authors: Vigh‐Teichmann I. , Petter H. , Vigh B.
Published: February 2007

Vigh‐Teichmann I, Petter H, Vigh B. GABA‐immunoreactive intrinsic and 4mmunonegative secondary neurons in the cat pineal organ. J Pineal Res 199 1 : 10: 18‐29.

The pineal organ of the cat was studied by postembedding gamma‐aminobutyric acid (GABA) immunocytochemistry. Two polyclonal rabbit GABA antisera were used with light microscopic peroxidase and electron microscopic immunogold techniques. A considerable number of intrinsic neurons are scattered in the proximal portion of the pineal organ. Some of the nerve cells were GABA‐immunoreactive; other neurons as well as pinealocytes and glial/ependymal cells were immunonegative. A few GABA‐immunoreactive neurons behaved like CSF‐contacting neurons by penetrating the ependymal lining of the pineal recess. GABA‐immunoreactive neurons were more frequently found in the subependymal region. Small bundles of thin immunoreactive unmyelinated and thick immunoreactive myelinated nerve fibers occurred in the proximal pineal, especially near the habenular commissure. There were synapses of various types between GABA‐immunoreactive and ‐immunonegative fibers. Myelinated immunoreactive axons seemed to loose their sheaths after entering the organ. Axon‐like processes of pinealocytes terminated on dendrites of immunonegative neurons present near the posterior and habenular commissures. The axons of these neurons were found to join the commissural fibers and may represent a pinealofugal pathway conducting information originating from pinealocytes. The pinealocytic axons forming ribbon‐containing synapses on dendrites of secondary neurons speak in favor of the sensory‐cell nature of the pinealocytes. The pinealopetal myelinated GABA‐immunoreactive axons and the intrinsic “GABA‐ergic” neurons are proposed to inhibit the action of intrapineal neurons on which the pinealocytic axons terminate.
Determination of the specific gravity of human pineal*
Authors: Bhatnagar Kunwar P. , Veling Maria , Ouseph P.J. , Nettleton G. Stephen
Published: February 2007

Abstract: Specific gravity values for the pineal gland in any species are lacking. These data are necessary for calculating and interrelating pineal weight and volume. This report deals with the specific gravity of human pineal gland. The specific gravity of fresh, unfixed human pineal has been determined to be 1.197 ± 0.036 SEM at 20°C (N = 11) using water as the measuring medium. By contrast, human brain has been reported in the literature to have a specific gravity of 1.036. Specific gravities of human pineals fixed in Bouin's fluid, Bouin's fluid followed by 80% ethanol, 80% ethanol, and embalming fluid were found to be 1.113 ± 0.025 (N = 5), 0.941 ± 0.009 (N = 5), 0.990 ± 0.022 (N = 3), and 1.149 ± 0.021 (N = 7), respectively. These are corrected values accounting for the specific gravities of the respective measuring fluids. It is shown that the specific gravity of human pineal as derived in this study is directly applicable to calculations of pineal volumes and weights not only in humans, but in other species as well.
Low ambient temperature does not affect the pineal concentrations of either 5‐methoxytryptamine or melatonin in golden hamsters kept under short photoperiod
Authors: Raynaud F. , Pévet P.
Published: February 2007

Abstract: This work investigates the rhythmic synthesis of pineal 5‐methoxytryptamine and related indoles in golden hamsters as a function of ambient temperature. 5‐methoxytryptamine, 5‐methoxytryptophol, 5‐methoxyindole acetic acid, and melatonin were measured by high pressure liquid chromatography (HPLC) in the pineal gland of golden hamsters after inhibition of monoamine oxidase. In our experimental conditions, the pineal 5‐methoxyindole concentrations of hamsters kept at 5°C were similar to those observed at 20°C. These results suggest that low temperature, which is known to accelerate the short photoperiod‐induced gonadal regression, acts at a level different to that of the pineal gland or affects another compound in the pineal gland.
Failure of single electroconvulsive shock to affect daytime melatonin production in rats
Authors: Monteleone Palmiero , Maj Mario , Orazzo Catello , Fusco Mario , Steardo Luca
Published: February 2007

Abstract: It has been reported that, in the rat, different types of stressful procedures increase daytime melatonin production. Electroconvulsive shock (ECS) has been shown not to affect daytime pineal melatonin in rats killed 9 hr after its administration. It is possible that the long‐lasting interval between the ECS administration and the sacrifice of the animals obscured an effect of the stressful procedure. In the present study, the effects of acute ECS on daytime melatonin production were evaluated in both ECS‐ and sham‐treated rats killed 30, 60, 120, and 240 min after treatment. As compared with the sham‐treated animals, rats receiving acute ECS (80 mA, 0.5 sec) did not show any significant difference in either pineal or serum melatonin levels at any time point after treatment. These data indicate that single ECS does not affect daytime melatonin production in the rat and suggest that the pineal gland may respond differently to the various stressful procedures.
Food restriction enhances melatonin effects on the pituitary‐gonadal axis in female rats
Authors: Wilamowska Agnieszka , Pawlikowski Marek , Klencki Mariusz , Kunert‐Radek Jolanta
Published: February 2007

Abstract: The effects of melatonin (25 μg s.c. daily in the late afternoon for 10 days) on the ovarian morphometry and the gonadotropin secretion were investigated in food‐restricted rats and rats fed ad libitum. In food‐restricted rats melatonin produced the significant decrease of the surface area of the ovary and of zona granulosa. Moreover, melatonin treatment of food‐restricted rats resulted in significant diminishment of the relative areas of Graafian follicles and zona granulosa estimated in relation to the ovary cross‐sectional surface area. On the other hand, melatonin did not produce significant alterations of the morphometric indices of the ovary in rats fed ad libitum. Melatonin administration was found to inhibit the effects of gonadoliberin on gonadotropin release in food‐restricted but not in normally‐fed rats. These findings suggest that food restriction sensitizes the pituitary‐ovarian axis to antigonadotropic melatonin action.
Characterization of a [3H]glutamate binding site in rat pineal gland: Enhanced affinity following superior cervical ganglionectomy
Authors: Kus Laura , Handa Robert J. , McNulty John A.
Published: February 2007

Abstract: Glutamate, an excitatory neurotransmitter/neuromodulator involved in cell‐to‐cell communication within the central nervous system, is now believed to play a role in neuroendocrine function. In this study we describe a single, saturable, stereospecific, and temperature‐, time‐, and pH‐dependent binding site for glutamate in the pineal gland of the rat (Kd= 612 ± 23 nM, Bmax= 3.17 ± 0.33 pmol/mg protein). After removal of the sympathetic innervation to the pineal gland, [3H]glutamate binding displayed a higher apparent affinity (Kd= 412 ± 28 nM) (P < 0.05) without a change in binding site number (Bmax= 3.60 ± 0.24 pmol/mg protein). No difference in [3H]glutamate binding site number was observed in pineal glands obtained from animals sacrificed during the middle of the light and dark periods. These data suggest a possible modulatory role for a glutamate binding site in pineal gland function.
Immunohistochemical study of the pineal astrocytes in the postnatal development of the cat and dog pineal gland
Authors: Boya Jesús , Calvo Jose Luis
Published: February 2007

Abstract: The expression of glial antigens vimentin (VIM) and glial fibrillary acidic protein (GFAP) is described in the pineal gland of cats and dogs from the first postnatal days to adulthood. VIM immunopositive cells were observed from the first postnatal days in both species. GFAP expression starts from the second postnatal week. In adults, a notable population of stellate cells immunopositive for GFAP and VIM was found dispersed throughout the gland. According to their immunocytochemical profile, these cells could be identified as astrocytes.
Minireview Current methodologies for the study of pineal morphophysiology
Authors: Welsh Marcia G.
Published: February 2007

Welsh MG. Current methodologies for the study of pineal morphophysiology. J Pineal Res 1994; 16: 113–120.

Light and electron microscopes, with or without the use of immunohistochemical techniques, have been the instruments of choice for study of the pineal complex even up to recent times. Other morphological technologies have become available during the past decade that, if applied to current questions concerning pineal morphophysiology, could add considerably to our understanding of this complex system. Those technologies discussed include confocal scanning laser microscopy (in conjunction with other techniques including immunohistochemistry and three‐dimensional reconstruction), tissue culture methodologies, carbocyanine dyes (i. e., DiI), in situ hybridization, and application of microinjection methodologies. It is suggested that these technologies will be necessary for morphophysiolo‐gists to not only collaborate with molecular biologists and biochemists who study the pineal complex, but to corroborate the molecular and biochemical results of our colleagues.
High melatonin solubility in aqueous medium
Authors: Shida CS. , Castrucci A. M. L. , Lamy‐Freund M. T.
Published: February 2007

Shida CS, Castrucci AML, Lamy‐Freund MT. High melatonin solubility in aqueous medium. J Pineal Res. 1994:16:198–201.

The pineal hormone melatonin (5‐methoxy‐N‐acetyl‐tryptamine) has been reported to participate in important physiological processes. Although some of its biological actions seem to depend on a protein receptor at the membrane surface, melatonin is known to interact with a large variety of tissues and cells, suggesting that the molecule may not necessarily interact through a specific membrane receptor at a specific cell. Most discussions of melatonin activity have assumed that the molecule is highly hydrophobic. Contrary to belief, the present work shows that melatonin is soluble in a purely aqueous medium up to 5 ± 10‐3 M and describes a new method of melatonin preparation which shows the high hydrophilicity of the molecule. The results presented will affect the current biological hypothesis on the need of a melatonin carrier in the blood stream or the mechanisms which allow the hormone to cross the cell membrane and interact at the level of the nucleus.
Characterization or the chicken brain melatonin‐binding protein using iodinated and triturated ligands
Authors: Kennaway David J. , Hugel Helmut M. , Rowe Shawn A.
Published: February 2007

Kennaway DJ, Hugel HM, Rowe SA. Characterization of the chicken brain melatonin‐binding protein using iodinated and triturated ligands. J. Pineal Res. 1994; 17: 137–148.

The melanoma‐binding protein in chicken brain membranes was characterized using both [125I]‐2‐iodomelatonin and [3H]‐melatonin as radioligands. Saturation studies conducted at 25°C revealed a single class of binding site with dissociation constants of 24 ± 4. 8 pM (n = 7) and 125 ± 21 pM (n = 6) for the iodinated and tritiated legends, respectively. Calculation of the affinity constant using data from kinetic experiments gave values of 2.2 ± 0.4 pM and 135 ± 15 pM for the iodinated and tritiated ligands, respectively. Competition studies showed that the rank order of inhibition of binding by melatonin analogues was similar for both radioligands (2‐iodomelatonin > melatonin > 2,3‐dihydromelatonin > N‐acetyl‐5‐methoxykynurenamine > N‐acetylserotonin > 5‐methoxytryptamine). The calculation of Ki, which depends upon the affinity constant, was 22 ± 4.9 pM and 129 ± 21 pM for 2‐iodomelatonin and melatonin, respectively, when the affinity constant derived from the [125I]‐2‐iodomelatonin saturation experiments was used, but 4.9 ± 1.5 pM and 33 ± 5.5 pM when the kinetically derived constant was used. When [3H]‐melatonin was used, the Ki for melatonin was 72 ± 8 pM and 20 ± 4.6 pM for 2‐iodomelatonin and melatonin. Binding of [125I]‐2‐iodomelatonin to the membranes was partially reversible at 25°C in contrast to the complete reversibility of [3H]‐melatonin. Examination of the effects of temperature on binding indicated that at 37°C both association and dissociation of both legends were accelerated. Closer examination showed that at 37°C there was a loss of approximately 40% of the [125I]‐2‐iodomelatonin binding sites and little influence upon the affinity of binding with time. By contrast, when [3H]‐melatonin was used, the affinity decreased fourfold, with only a slight change in the number of sites. If membranes were incubated at 37°C and then switched 25°C, binding increased, emphasizing the fact that the binding sites were not destroyed. Whereas there appears to be little doubt that 2‐iodomelatonin is a biologically active melatonin agonist, the binding of the radioactive form of this agonist to the putative melatonin receptor binding site is quite different from that of the endogenous ligand. This may have serious consequences in studies where receptor content is determined following physiological or pharmacological interventions.
Effects of single doses and daily melatonin treatments on serotonin metabolism in rat brain regions
Authors: Miguez J. M. , Martin F. J. , Aldegunde M.
Published: February 2007

Miguez, JM, Martin F. J, Aldegunde M. Effects of single doses and daily melatonin treatments on serotonin metabolism in rat brain regions. J. Pineal Res. 1994; 17:170–176.

The acute effects of two doses (0. 5 and 1 mg/kg) of melatonin on the levels of tryptophan, serotonin, and 5‐hydroxyin‐doleacetic acid in several rat brain regions were studied. Tryptophan content in the brain regions was unchanged by the treatments. Melatonin at a dosage of 0. 5 mg/kg increased medial hypothalamic serotonin levels at 60 and 90 min after the injection. However, the dose of 1 mg/kg increased the levels of this amine or its metabolite in the preoptic area‐anterior hypothalamus, medial and posterior hypothalamus, amygdala, and midbrain. These results suggest a specific regional sensitivity to melatonin as well as a dose‐dependent response. The stimulatory melatonin effect on the serotoninergic system was also observed after a daily treatment with this hormone (0. 5 mg/kg, twice daily during 10 days) in both intact or pinealectomized rats. In intact rats, melatonin treatment increased the levels of 5‐hydroxyindole‐3‐acetic acid in the preoptic area‐anterior hypothalamus and medial hypothalamus, while in pinealectomized rats melatonin increased the serotonin content in the medial hypothalamic region. The data support the idea that melatonin has a selective action on serotonin metabolism in regions that contain serotoninergic terminals, especially at medial hypothalamic level.
Structure of the pineal gland in the adult cat
Authors: Boya Jesús , Calvo Jose Luis , Rancano Dolores
Published: February 2007

Abstract: The ultrastructure of the pineal gland in the adult cat is described and compared with that of other mammals. Connective tissue spaces showed capillar‐ies with nonfenestrated endothelia and numerous unmyelinated nerve fibers. In the proximal region of the gland, myelinated nerve fibers coming from the anterior commissure were also found. Cat pinealocytes showed a nucleus with prominent nucleoli, a well developed Golgi apparatus, centrioles, granular endoplasmic reticulum, ribosomes, abundant microtubuli and enlarged mitochondria. Pinealo‐cytes showed several long processes with bulbous endings filled with clear vesicles and scarce “synaptic” ribbons. Pineal astrocytes and their processes were characterized by the presence of abundant filaments.
The long‐term effect of pinealectomy on the crypts of the rat gastrointestinal tract
Authors: Callaghan B. D.
Published: February 2007

Abstract: Previously it has been found that rat small bowel crypt cell hyperplasia occurred several weeks after pinealectomy. To determine if this effect was longer‐lasting (because of the possible role of the pineal in bowel malignancy) the crypt cell proliferation rate was determined in rat small bowel and colon 6 months after pinealectomy, using a stathmokinetic technique. Although the hyperproliferative effect of pinealectomy was well maintained in the small bowel crypts after 6 months, the hyper proliferative effect in the colonic crypts was much less marked. There is no obvious explanation for these findings, although it is possible that regional differences in levels of gut neuropeptides or melatonin are involved. The mechanism of the effect of pinealectomy on the crypts remains unexplained—in particular, why the effect is so prolonged.