bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Effects of Superior Cervical Ganglionectomy on Dimethylbenz(a)anthracene‐Induced Mammary Tumors in the Rat
Authors: Chang Nada , Spaulding Timothy S. , Tseng Michael T.
Published: February 2007

The role of the pineal in regulating the oncogenic processes was explored in Sprague‐Dawley female rats by comparing incidence and growth of mammary tumors in animals subjected to superior cervical ganglionectomy (SCGx) or blinding and anosmia (BAs) with that of intact rats treated with 7–12‐ dimethylbenz(a)anthracene (DMBA). The surgery was performed at the age of 56 days, 1 day following the administration of the carcinogen. Growth of mammary tumors was studied, and 15 weeks later the rats were sacrificed by decapitation and the activity of the pineal hydroxyindole‐O‐methyltransferase (HIOMT) was determined. Carcinostatic effects of similar magnitude were present in both SCGx and BAs groups as evident from tendency toward reduced tumor incidence and decreased total tumor mass. Ganglionectomized rats developed significantly smaller numbers of tumors than intact control animals. A trend toward reduced tumor number and increased tumor regression was evident in the BAs group. Although there was no significant difference in tumor volumes among the groups, BAs animals showed a distinct trend toward smaller tumor volumes at the termination of the experiment. Despite similar carcinostatic tendencies, SCGx rats had significantly lower HIOMT activity than BAs animals. The possible existence of multiple carcinostatic mechanisms in BAs and SCGx rats is discussed.
Pineal Dependence of the Syrian Hamster's Nocturnal Serum Melatonin Surge
Authors: Vaughan George M. , Reiter Russel J.
Published: February 2007

The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy in male Syrian hamsters. Ganglionectomy and pinealectomy each prevented the nocturnal rise of serum melatonin concentration seen in control animals. The normal nocturnal surge of circulating inelatonin in this species appears to depend on the pineal gland and its sympathetic innervation.
Effects of Chemical and Surgical Ganglionectomy on Electrical Activity of the Pineal Gland of Male Rats
Authors: Reuss Stefan
Published: February 2007

In order to elucidate further the role of sympathetic innervation for pineal function, the influence of sympathectomy on the spontaneous electrical activity of single cells in the pineal gland of adult male rats was investigated. Extracellular single‐unit recordings were made during nighttime in the pineal gland of urethane‐anesthetized, blinded adult male rats that had been treated neonatally with 6‐hydroxydopamine, or that were ganglionectomized either during, or 12–16 h or 36–40 h, prior to the recording experiment. These experiments revealed that the excitatory influence of the sympathetic system on pineal nocturnal electrical activity can be abolished by either chemical sympathectomy of neonatal rats or surgical superior cervical ganglionectomy in adult animals.
Circadian Rhythms in Lizards: Phase Response Curve for Melatonin
Authors: Underwood Herbert
Published: February 2007

Single biweekly injections of melatonin were administered to lizards (Sceloporus occidentalis) free‐running (exhibiting their endogenous circadian activity rhythm) in constant dim illumination. The injections caused phase shifts in the activity rhythm whose magnitude and direction were a function of the time of the melatonin injections, relative to activity onsets. Plotting the direction and amount of phase shift versus the time (phase) at which the injection was given generates a phase‐response curve (PRC). The PRC shows that injections administered between midsubjective day and early subjective night (6–15 hr after activity onset) elicit phase advances in the activity rhythm, whereas injections given at other phases of the activity cycle induce phase delays. The existence of a PRC for melatonin suggests that the daily endogenous rhythm of melatonin (i. e., of pineal origin) may be involved in phasing, or entraining, the circadian system of lizards. The shape of the PRC also allows predictions as to the effects of continuous exogenous melatonin administration on the period of free‐running activity rhythms as well as on the mechanism of entrainment of activity rhythms to daily melatonin injections.
Melatonin Lowers Plasma Prolactin Levels in Female Red Deer (Cervus elaphus)
Authors: Adam Clare L. , Atkinson Terence , Moir Carol E.
Published: February 2007

The aim of the study was to determine the effect of exogenous melatonin treatment on circulating prolactin levels in red deer. Melatonin was administered from 12 June 1984 (day 1) to lactating and non‐lactating hinds in the feed daily at 1600 h, and to non‐lactating hinds by a subcutaneous implant. Average concentrations (ng/ml) of prolactin in plasma taken serially over 15‐h periods were significantly higher for untreated hinds than for melatonin‐treated animals on day 15 whether lactating (66–133 v. 23–28, P<0.05) or non‐lactating (28–174 v. 8–13, P< 0.01), remained higher on day 36 (lactating: 41–152 v. 15–21, P< 0.05; non‐lactating: 21–50 v. 1–7, P<0.001) but had decreased to similar levels on day 72 (lactating: 5–24 v. 7–17; non‐lactating: 2–9 v. 0–4).

The advanced reduction in plasma prolactin for all melatonin‐treated hinds was associated with an advanced onset of seasonal breeding activity.
Pinealocyte Dense‐Cored Vesicles and Synaptic Ribbons: A Correlative Ultrastructural‐Biochemical Investigation in Rats and Mice
Authors: McNulty J.A. , Fox L.M. , Lisco S.J.
Published: February 2007

Dense‐cored vesicles (DCV) and synaptic ribbons (SR) were quantified in the pineal gland of the rat (Sprague‐Dawley) and mouse (Sasco/ ICR strain), and day/ night differences in frequency of these organelles correlated with levels of indoles determined by high performance liquid chromatography (HPLC). There were significant day/night differences in levels of serotonin (5HT), 5‐hydroxyindole acetic acid (5HIAA), N‐acetyl‐5HT, and melatonin in the rat gland. Melatonin and N‐acetyl‐5HT were not detectable in the mouse gland sampled every 4 h over the light:dark cycle. The concentrations of 5HT and 5HIAA (ng/μg protein) were similar in light‐adapted rats and mice, but these indoles did not exhibit a circadian rhythm in the mouse gland. Correlative ultrastructural/biochemical results suggest that DCV do not contain physiologically important stores of 5HT since 1) the mouse gland contains the same number of DCV as the rat during the daytime, but only one‐tenth the levels of 5HT, 2) day/night 5HT levels do not vary in the mouse gland, but there is a significant nocturnal decline in DCV numbers, and 3) 5HT levels in the rat gland decline at night when DCV numbers increase. Numbers of SR were significantly elevated at night in the rat and mouse, and the frequency of this organelle was similar in both species. However, ribbon‐type SR predominated in rat pinealocytes, whereas SR in the mouse were almost exclusively spherical in shape. Day/night diffferences in SR numbers in the mouse gland suggest that cellular mechanisms regulating the frequency of this organelle do not involve factors related to indole metabolism. Because of the lack of photoperiodic effects on indole metabolism in the mouse pineal gland, this species is a potentially important model to study the functional relationship of pinealocyte organelles to cyclical changes in pineal products other than indoles (e.g., peptide/ protein factors).
Detailed Diurnal Rhythm of Sensitivity to Melatonin Injections in Turkish Hamsters, Mesocricetus brandti
Authors: Hong Seung M. , Stetson Milton H.
Published: February 2007

A diurnal rhythm of sensitivity to exogenous melatonin was defined in adult male Turkish hamsters, Mesocricetus brandti. Melatonin was administered daily by subcutaneous injections (15 μg in 0.1 ml 10% ethanolic saline) for 10 weeks in animals exposed to 16 L:8 D. As in golden and Djungarian hamsters, two periods of melatonin sensitivity were identified. The first, in late afternoon, persisted for 6 hr, from 7 hr to 1 hr before lights off. The second period was briefer, of only 2 hr duration in the late night, terminating at the time of lights on. Melatonin injections given during these sensitive periods promoted testicular regression in most animals; melatonin administered at other times of the day was without effect on testicular function in most animals of these groups. Gonadal regression induced by properly timed melatonin injections was rapid, in many groups nearly complete in 6 to 7 weeks. The results are discussed in relation to the function of pineal melatonin in photoperiodic time measurement in hamsters.
[3H] Melatonin Binding in Membrane and Cytosol Fractions From Rat and Calf Brain
Authors: Niles Lennard P.
Published: February 2007

The binding characteristics of the tritiated pineal hormone, [3H] melatonin, were studied in brain tissues using in vitro binding techniques. In synaptosomal membranes prepared from rat hippocampus and subjected to preincubation at 37°C and multiple washings, high‐affinity binding of [3H] melatonin significantly exceeds that previously reported for membrane or cytosol fractions from mammalian brain. Scatchard analysis of saturation binding data indicates that binding affinities are similar in membrane (Kd= 15 nM) and cytosol (Kd=11 nM) preparations. However, binding is about sevenfold greater in membranes than in cytosol prepared by centrifugation of homogenates at 104,000g for 60 min. Specific binding is also present in both particulate and soluble fractions from calf brain.

Inhibition experiments, in rat hippocampal membranes, indicate that norepinephrine is the most potent inhibitor of about 55% of total binding. Serotonin also exhibited high affinity for about 25% of total binding, suggesting that [3H] melatonin labels both adrenergic and serotonergic sites in this brain region.

Further studies are required to characterize the serotonergic and adrenergic sites labelled by [3H] melatonin and to determine whether these sites are functionally important receptors for melatonin.
Day‐Night Differences in the Number and Structure of Synaptic Ribbons in Chick Pineal
Authors: Robertson George N. , Dickson D. Howard
Published: February 2007

The objective of this study was to evaluate the effect of lighting (day‐night) changes on pinealocyte synaptic ribbon shape (conformation) and numbers. Three‐dimensional reconstruction analysis of pinealocyte basal processes revealed that 30% (6/20) of all ribbons from dark‐adapted animals were either curved or split. Synaptic ribbons from light‐adapted animals did not show this variant morphology; all were linear structures. An analysis of each section from each series, containing curved or split ribbons, revealed that 44% (16/36) of all ribbon profiles would yield inflated counts if used in random morphometric sampling protocols. Therefore, split and curved (variant) ribbon morphologies could result in an overestimation of synaptic ribbon populations of approximately 13% (0.44 × 30%) of dark‐adapted samples. In spite of this potential sampling error, the fourfold increase in the number of synaptic ribbons observed during the dark phase of a light‐dark cycle remains highly significant (P < 0.0001).
Effect of Various Cations on the Activity of Pineal Gland N‐Acetyltransferase (EC 2.3.1.5) and Hydroxyindole‐O‐Methyl Transferase (EC2.1.1.4) In Vitro
Authors: Morton Dougal J.
Published: February 2007

The effect of various cations on activity of hydroxyindole‐O‐methyltransferase (HIOMT) and N‐acetyltransferase (NAT) from pineal gland was studied. Copper inhibited both enzymes while calcium and magnesium inhibited HIOMT; the mechansims of these inhibitions are unknown at this stage. Calcium, magnesium, potassium, and sodium initially stimulated NAT activity, and as the cation concentration increased inhibitory activity was observed. These differential effects on NAT activity may in some way be involved in pineal regulation of cation levels.
Effect of Pinealectomy on Thyroid Hormone (T4 and T3) Levels in Plasma During Annual Reproductive Cycle in the Freshwater Catfish, Clarias batrachus
Authors: Nayak P.K. , Singh T.P.
Published: February 2007

Thyroxine and triiodothyronine (T3) were measured by radioimmunoassay in serum and thyroid gland of the freshwater teleost Clarias batrachus. Pinealectomy increased the glandular levels of the thyroid hormones but decreased the plasma levels of T4 concomitantly with the increase of T3 levels. Most of the effects of pinealectomy on thyroid hormones were restricted to the gonadal development periods. Pinealectomy has shown no significant impact on thyroid hormones during the other periods of the reproductive cycle. Thus, it appears that the pineal gland is inhibitory to thyroid hormones during gonadal development and maturation.
Adrenalectomy Prevents Changes in Rat Pineal Melatonin Content N‐Acetyltransferase Activity Induced by Acute Insulin Stress
Authors: Tannenbaum Michael G. , Reiter Russel J. , Vaughan Mary K. , Troiani Maureen E. , Gonzalez‐Brito Aldo
Published: February 2007

The activity of N‐acetyltransferase (NAT) the content of melatonin (MEL) in the rat pineal have been shown to be sensitive to several types of stressors. This study was designed to assess the role of the adrenals in mediating the effect of one such stressor, insulin‐induced hypoglycemia, on pineal synthetic activity. Intact bilaterally adrenalectomized (ADX) adult male rats were kept under light:dark cycles of 14:10 (lights on 0600 h) injected intraperitoneally with 10 IU insulin at 1300 h, groups (n = 8) were killed 2, 3, or 4 h postinjection. Plasma catecholamines were assayed by means of high performance liquid chromatography radioimmunoassay was used to assess pineal NAT activity MEL content. All injected groups were rendered hypoglycemic by insulin administration. Compared to uninjected controls, plasma epinephrine in hypoglycemic intact rats rose after 2 h, whereas epinephrine did not change in hypoglycemic ADX animals. The increase in epinephrine in intact animals was correlated with a rise in NAT activity at 2 h. Moreover, pineal MEL content at 2, 3, 4 h was significantly greater than control values. In contrast, no changes in pineal biosynthetic function were found in ADX rats. This differential response by intact ADX rats suggests that an adrenal product (possibly epinephrine) is responsible for mediating the stimulatory effects of acute insulin‐induced hypoglycemic stress on the rat pineal.
Plasma Melatonin Levels in Patients Suffering From Colorectal Carcinoma
Authors: Khoory Roderich , Stemme Dietmar
Published: February 2007

Plasma melatonin was determined in samples of patients with colorectal carcinoma and in controls using an iodinated radioimmunoassay. Both groups showed large individual variability in absolute melatonin levels. However, during the night, melatonin concentration in cancer patients was significantly lower than in controls.
Influence of Dexamethasone on Nocturnal Melatonin Production in Healthy Adult Subjects
Authors: Demisch Lothar , Demisch Klaus , Nickelsen Thomas
Published: February 2007

There is no conclusive evidence supporting an interaction between the pineal gland and the hypothalamic‐pituitary‐adrenal axis. In this study, 11 healthy adults (six women, five men; aged 18–47 years) received a placebo the first night and 1 mg dexamethasone the next night at either 1800 or 2300 h. Administration of 1 mg of dexamethasone was followed by an attenuation of the nocturnal production of melatonin in 9 of 11 subjects. A significant reduction was found between melatonin plasma levels before and after dexamethasone at 0400h (P < 0.01, t test for dependent groups). It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.
Action of Morphine on Melatonin Release in the Rat
Authors: Esposti D. , Esposti G. , Lissoni P. , Parravicini L. , Fraschini F.
Published: February 2007

Some data from the literature raised the possibility of an interaction between the opioidergic system and pineal secretion. The present study was undertaken in order to investigate the acute influence exerted by opioids upon plasma melatonin levels in the albino rat. Different doses of morphine hydrocloride were injected (1, 1.5, 2, 3 mg/kg) intraperitoneally into anaesthetized adult male rats bearing a cannula previously inserted into the carotid. Blood samples were collected subsequently at 30‐min intervals, within a period of 90 min following drug administration. Plasma melatonin contents were determined by a radioimmu‐noassay (RIA) method. Acute administration resulted in a dose‐dependent increase in plasma melatonin concentration when compared to the respective controls. This effect is blocked by pretreatment with Naloxone. The present result seem to support the hypothesis that the opioidergic system, in certain circumstances, might contribute to the activation of melatonin secretion.
Interactive Effects of Stress and Photoperiod History on Gonadal Condition in Male Syrian Hamsters
Authors: Rusak Benjamin
Published: February 2007

A study of the effects of melatonin injections given to male Syrian hamsters (Mesocricetus auratus) late in the light phase in a 14L:10D photoperiod included control, oil‐injected hamsters that had been transferred from a 16L:8D photoperiod. Many oil‐injected hamsters underwent gonadal regression under these conditions. A literature review indicated that endocrine effects of‘control’injections are fairly common but that they might depend on previous photoperiodic history. A second study found that hamsters born and raised in 16L:8D had larger testes at 150 days of age than those raised in 14L:10D. Transfer from 16L:8D to 14L: 10D caused some unhandled hamsters to show gonadal regression while transfer to 14L:10D combined with daily oil injections caused most hamsters to undergo gonadal regression. Injections in animals maintained in 14L:10D throughout the study did not cause gonadal regression.

These results indicate that stress effects can confound interpretation of drug treatments that require daily injections. They also demonstrate that the endocrine system of male Syrian hamsters distinguishes two photoperiods that are longer than the critical daylength (12.5 h). The effects of shortening daylengths may be potentiated by environmental stressors; together these may trigger gonadal regression at variable annual phases in anticipation of the critical daylength.
Photoperiodic Sensitivity of Prepubertal Female Fisher 344 Rats
Authors: Leadem Christopher A.
Published: February 2007

The laboratory rat is thought to be a poor model for study of the photoperiodic control of reproduction; however, this has only been investigated in a few rat strains. The purpose of the present investigation was to determine if the neuroendocrine‐reproductive system of the Fisher 344 (F344) rat, an inbreed strain, is sensitive to light deprivation. All treatments were performed on 28‐day‐old female F344 rats and the animals maintained for 8 weeks in a 14:10 light: dark cycle. Blinding resulted in a 65% (P < 0.01) reduction in uterine weight and a 25% (P < 0.01) decrease in ovarian weight. Accompanying these reductions in blinded animals were significant inhibitions of anterior pituitary weight, serum prolactin levels, and pituitary prolactin synthesis as measured in vitro. Pinealectomy of the blinded animals prevented all of these effects. Additionally, when olfactory bulbectomy, a procedure known to sensitize rats to the effects of photoperiod, was combined with blinding, the results did not differ significantly from that found with blinding alone. From these data we conclude that 1) the neuroendocrine‐reproductive system of the prepubertal F344 female rat is highly sensitive to light deprivation; 2) light deprivation produces its antigonadotrophic effect through the pineal gland; and 3) olfactory bulbectomy does not potentiate the effects of blinding in the F344 rat.
Effect of Selective Monoamine Oxidase Inhibitors on Rat Pineal Melatonin Synthesis In Vitro
Authors: Oxenkrug G. , McIntyre I. , McCauley R. , Yuwiler A.
Published: February 2007

Freshly cultured pineal glands respond to the monoamine oxidase A (MAO A) inhibitor clorgyline and to high concentrations of the MAO B inhibitor, deprenyl, with an increase in serotonin N‐acetyltransferase activity and N‐acetylated indoles and a fall in 5‐hydroxylated serotonin degradation products. Glands cultured for 48 hours before challenge respond less. Response is absent in glands cultured for 72 hours and in glands from ganglionectomized animals cultured for 48 hours before challenge. These data are consistent with the hypothesis that these MAO inhibitors stimulate melatonin synthesis by protecting norepinephrine from degradation.
Subneuronal Fate of Intracerebroventricular Injected 3H‐Melatonin
Authors: Anton‐Tay Fernando , Forray Carlos , Ortega‐Corona Bertha G.
Published: February 2007

The fate of 3H‐melatonin after its intracerebroventricular administration was studied both in different brain regions and in subcellular fractions. The rate of disappearance of 3H‐melatonin from the brain was found to be multiphasic. Forty‐eight h after a 3H‐melatonin injection, radioactivity was still present in the brain. Nonlinear regression analysis of the data confirmed a very rapid half‐life component and (t½= 3.04 min) a slower one (t½= 36 min). We also found a much slower component (t½= 24 h), however. Considerable metabolism of melatonin was detected since only 36.5% of administered radioactivity remained as melatonin at 45 min. The subcellular distribution of the radioactivity present in the brain at all times studied showed that a major proportion of the radioactivity remained in the cytosol and respectively decreasing proportions in the 900g pellet, mitochondrial pellet, and the microsomes.

The radioactivity remaining in the cytosol at 45 min was found to coelute with a macromolecule that was resolved by gel filtration and could be displaced by previous melatonin administration. Purified nuclei retained 0.71% of the radioactivity at 45 min; of this total, 73% was KC1 extractable. Our data suggest the presence of a binding site in the cytosol and in the nucleus. The presence of 3H‐melatonin up to 48 h after its administration may account for melatonin's long‐term effects on brain function.
Pineal Gland and Humidity Effects on Testicular Function of the Indian Palm Squirrel, Funambulus pennanti
Authors: Haldar Chandana , Saxena Nayni
Published: February 2007

The effect of two different conditions of humidity (80 ± 5% and 40 ± 5%) under stimulatory photoperiod (14L/10D) and high temperature (38 ± 2°C) was studied on the testes and accessory sex organs of the Indian palm squirrel, Funambulus pennanti, during the sexually active phase. High humidity (80 ± 5%) reduced significantly the testes weight of the sham‐operated animals as compared to the controls under natural environmental conditions but had no effect on that of pinealectomized animals. Moderate humidity (40 ± 5%) did not affect the testes of sham‐operated as well as pinealectomized animals, as compared to the respective controls. The seminal and prostatic weights showed no significant difference in high or moderate humidity conditions. However, the epididymal weight of the animals exposed to high humidity was significantly reduced in sham‐operated animals only. Thus, these results indicate that the pineal gland may be implicated in mediating the humdity information to control the male gonadal function in the Indian palm squirrel, Funambulus pennanti.
Rapid and Simple Synthesis for the Sulphate Esters of 6‐Hydroxy‐Melatonin and N‐Acetyl‐Serotonin
Authors: Leone A. M. , Francis P. L. , McKenzie‐Gray B.
Published: February 2007

Melatonin is metabolised by hydroxylation at the 6 position and to a variable extent by demethylation. Both metabolites so formed are excreted as sulphate and, to a lesser extent, glucuronide conjugates. To authenticate these metabolites which we had earlier isolated from urine, we wished to have synthetic samples. Since we also required them as standards we needed them as powders. A review of the literature showed that there were only two published methods, of which only one gave rise to 6‐sulphatoxy‐melatonin (SaMT) as a solid.

The other metabolite, N‐acetyl‐serotonin‐sulphate (SNAS), has not been previously made, and we here describe some of its chemical properties. Our method modifies a published method taking into account the results given in a recent paper describing the sulphation of the thyroid hormones, T3 and T4. Hydroxy‐melatonin is thus reacted with a complex formed from dimethylformamide and chlorosulphonic acid. The reaction is of interest since it is rapid, easy, and produces pure powdered material in excellent yield.
Modulating Action of Melatonin on Serotonin‐Induced Aggravation of Ethanol Ulceration and Changes of Mucosal Blood Flow in Rat Stomachs
Authors: Cho Chi H. , Pang Shiu F. , Chen Bao W. , Pfeiffer Carl J.
Published: February 2007

Effects of melatonin and serotonin on ethanol ulceration and mucosal blood flow in the rat stomach were investigated. Melatonin and serotonin (5‐HT) administration did not produce observable gastric injury in the ex vivo stomach, but the 5‐HT dose dependently reduced glandular mucosal blood flow (GMBF) in this organ. Ethanol depressed GMBF and induced visible glandular mucosal injury. The latter effect was prevented by melatonin preincubation. Serotonin pretreatment aggravated the gastric mucosal injury and GMBF changes induced by ethanol; these actions were partially reversed by melatonin. The findings indicate that the GMBF and gastric injury are related; the reduction in GMBF, however, may not be the sole factor responsible for ulceration. The antagonistic effects of melatonin on 5‐HT action on the stomach suggest that melatonin may act as a modulator for 5‐HT action on the gastrointestinal tract.
Stereological Changes in Rat Ventral Prostate Induced by Melatonin
Authors: Srivilai Wannee , Withyachumnarnkul Boonsirm , Trakulrungsi Wantanee
Published: February 2007

Effects of melatonin on the ventral prostate of castrated rats supplemented with testosterone were studied using light microscopy. Stereological measurements were made of volume fractions of acini and stroma and surface fractions of glandular epithelium. From these figures and the weights of the glands, the volumes and surface areas were calculated, as well as the mean epithelial heights, mean acinar diameters, and mean distances between glandular acini. Doses of melatonin were varied, to verify its physiological and pharmacological effects. Castration without hormonal treatments produced atrophic changes, with decreases in acinar and stromal volume and widenings in the mean distances between the acini. None of these measurements differed among intact controls, sham‐operated controls, and testosterone‐supplemented castrated rats. In the castrated rats receiving both testosterone and melatonin, however, there were changes according to the doses of melatonin given. The animals receiving low doses of melatonin (50 and 400 μg daily) showed significant decreases in the volumes of the stroma and epithelium and the height of the epithelium. These stereological changes occurred without a significant reduction in the prostatic weights. The animals receiving the higher dose (800 μg daily) of melatonin showed no difference in any measurement compared with those of the testosterone‐supplemented castrated rats. In rats receiving 2,000 μg of melatonin daily, there were significant reductions in the weights of the prostates and the volumes of the acini. These results suggest a direct action of melatonin on the ventral prostate, and the effects depend on the dose given.
Seasonal Variation in the Daily Pattern of Plasma Melatonin in a Wild Mammal: The Mountain Hare (Lepus timidus)
Authors: Iason Glenn R. , Ebling Francis J. P.
Published: February 2007

Seasonal differences in daily patterns of plasma melatonin concentration were investigated in both free‐living and captive mountain hares, in relation to reproductive activity. There was a marked increase in plasma melatonin concentrations at night at all times of the year. The period of elevation of plasma melatonin above the daytime values was longer in winter than in summer, correlating with the longer duration of darkness. The magnitude of the nighttime rise in melatonin concentrations did not differ significantly between seasons. There was no change in the plasma melatonin profile under similar photoperiods before the summer solstice when hares are sexually active or after the summer solstice when gonadal regression occurs, indicating that melatonin is not directly pro‐ or antigonadal. These field and laboratory observations support the view that the daily rhythm of melatonin secretion plays a role in the transduction of photoperiodic information in the mountain hare. Furthermore, they favor the hypotheses that the circadian melatonin rhythm transduces photoperiod information by means of the duration of nocturnal melatonin secretion or by the coincidence of elevated melatonin with a particular sensitive period, rather than by the amplitude of the nocturnal rise.
Improved Procedures for Pineal Gland Fixation for Electron Microscopy
Authors: Schultz R.L. , Whitter E.F.
Published: February 2007

The common procedures used for preparing some organs and tissues for electron microscopy, in which a fixative with the buffer portion adjusted to near‐isotonicity to plasma is perfused in vivo, causes intolerable shrinkage of rat pineal cells. The present study was undertaken to optimize the parameters involved in the fixation of the pineal gland. The buffer and its concentration and the aldehyde or aldehydes used were among the variables investigated. The buffers tried were phosphate, cacodylate, PIPES, and HEPES. Decreasing the buffer concentration prevented shrinkage with all four buffers. The optimum concentrations were 0.05 M phosphate, 0.07 M cacodylate, 0.05 M or 0.057 M PIPES, and 0.1 M HEPES. PIPES and HEPES were clearly superior in retaining cytoplasmic density when compared with phosphate or cacodylate. The use of lithium PIPES and HEPES instead of the sodium equivalents enhanced membrane detail. A small volume of more concentrated aldehyde fixative perfused ahead of the main perfusate (a strong prewash) definitely helped prevent shrinkage. Using a mixture of aldehydes consisting of glutaraldehyde, formaldehyde, and acrolein reduced the tendency for shrinkage when compared with glutaraldehyde only. Some of the shrinkage space artefacts could be easily misinterpreted as normal features. Since the pineal gland commonly contains degenerating structures, a dependable fixation procedure is particularly needed. Also, accurate preservation is essential in the evaluation of physiological changes.
Effects of Melatonin and Thyroxine Treatment on Reproductive Organs and Thyroid Hormone Levels in Male Hamsters
Authors: Creighton Julia A. , Rudeen P. Kevin
Published: February 2007

The effects of exogenous thyroid hormone administration on melatonin‐induced gonadal atrophy were studied in young adult male hamsters. Animals were given daily afternoon injections of 25 μg melatonin and/or thrice‐weekly injections of 7 μg thyroxine. A control group received injections of saline vehicle only. No significant effect of either treatment was seen on body weight. Melatonin‐treated animals had significantly reduced testicular and seminal vesicle weights, compared with vehicle‐treated control animals: serum T4 levels and the FT4I were reduced by melatonin treatment, but serum T3 and the FT3I were increased. No effect of melatonin was seen on in vitro T3 uptake. Thyroxine treatment alone, while leading to elevated serum T4 levels and FT4I, had no effect on T3, the FT3I, or T3 uptake. Thyroxine treatment normalized circulating T4 levels and the FT4I in melatonin‐treated animals, without preventing the melatonin‐induced testicular regression. The results are taken as evidence that the inhibitory effects of melatonin on gonadal and thyroid function are independently mediated.
Partial Purification of a Polypeptide Extract Derived From Ovine Pineal That Suppresses the Growth of Human Melanoma Cells In Vitro
Authors: Noteborn H.P.J.M. , Weusten J.J.A.M. , Bartsch H. , Bartsch C. , Flehmig B. , Ebels I. , Salemink C.A.
Published: February 2007

A combination of gel filtration and reverse‐phase high performance liquid chromatography with postcolumn antitumour assay has been developed. A melatonin insensitive human melanoma cell strain was used to guide the purification of the antitumour effect of an ovine pineal aqueous extract (MW 1,000 to 10,000) that possessed the ability to decrease the hypophysiotropic activity of rat and mice hypothalami in vitro. This allows a specific identification of a pined factor (MW 2,000 to 6,000) that inhibits the growth of human melanoma cells at a dose of 0.47 mg/ml medium. It was shown that the activity of this pineal compound differs from structures known to be present in the pineal, such as melatonin, pteridines, and β‐carbolines. There appears to be evidence for a peptidic nature of this pineal antitumour factor.
Pineal Response in the Cichlid Fish Oreochromis mossambicus to Extreme Osmolality, pH, and Temperature
Authors: Relkin Richard
Published: February 2007

Unusually large pineal glands have been observed in Oreochromis alcalicus grahami of Lake Magadi, Kenya. To test the hypothesis that this phenomenon could result from the extremes of osmolality, pH, and temperature found in the lake, Oreochromis mossambicus males were exposed to either high osmolality (564 mOsm/L), high pH (10. 08), or high temperature (40 C); control groups were exposed to 7 mOsm/L at a pH of 7. 89 and a temperature of 26 C. After 21 days in the adverse environments, fish in all the experimental groups had significantly higher pineal weights and serum melatonin levels than the control fish. It is concluded that pineal activity increases in response to these environmental stresses, as it has been shown to increase with certain other types of stress.
Influence of Melatonin and iV‐Acetylserotonin on the Cyclic AMP Concentration in the Rat Thyroid Lobes Incubated In Vitro
Authors: Lewiński A. , Sewerynek E. , Zerek‐Meteń G. , Kunert‐Radek J. , Pawlikowski M. , Karasek L.
Published: February 2007

Effects of melatonin and N‐acetylserotonin on the cyclic AMP (cAMP) concentration in the organ‐cultured rat thyroid gland were investigated. Exposure of the thyroid explants to melatonin (10−8M) resulted in a decrease of cAMP levels. Melatonin at higher concentrations (10−7M and/or 10−6M) failed to influence the thryroid cAMP level. N‐acetylserotonin (10−6M), like melatonin in the lowest concentration employed, reduced cAMP concentrations in the thyroid explants when compared with controls. Unexpectedly, melatonin (at a concentration of 10−7M) added to the incubation medium with TSH (60 mU/ml), decreased the cAMP concentration in the thyroid compared with the group exposed to melatonin (10−7M) alone.
Effects of Isoproterenol on Synaptic Ribbons in Pinealocytes of the Rat and C57BL/6J Mouse
Authors: McNulty J A. , Prechel M. M. , Van de Kar L. D. , Fox L. M.
Published: February 2007

Synaptic ribbons (SR) in melatonin‐deficient pinealocytes of the C57BIV6J mouse were quantitatively compared to SR in pinealocytes of the rat after β‐adrenergic receptor activation by isoproterenol. Two populations of SR comprising synaptic spherules (SRsp) and synaptic rods (SRr) were described in both the mouse and the rat, but species differences existed in the ratio of SRr to SRsp. Isoproterenol caused a significant increase in frequency of SR of the rat but had little or no effect on SR populations in the mouse. It is unlikely that β‐adrenergic receptors are absent on mouse pinealocytes or were not activated since isoproterenol elevated plasma renin concentrations indicating activation of β‐adrenergic receptors. Furthermore the pineal of both species receives heavy sympathetic input. These findings indicate that the role and regulation of pinealocyte SR are complex and are functionally linked to β‐adrenergic receptors as well as other mechanisms related to the production of melatonin.
Unusual Ultrastructural Features in the Superficial Pineal Gland of the Yellow‐Bellied Country Rat (Rattus losea Swinhoe)
Authors: Huang Hung‐Tu , Lin Huai‐San , Sun Jih‐Hsing , Wang Po‐Yu
Published: February 2007

The ultrastructure of the superficial pineal gland of the yellow‐bellied country rat (Rattus losea Swinhoe), living under natural climatic conditions at the margin of the tropical region, was stuthed with special reference to the seasonal changes. In the rainy season with average monthly rainfall of 400 mm (light phase of 13.5 h, and temperature of 28°C) the gland was characterized by the presence of frequent large vacuoles containing flocculent material (LVFs), large condensed inclusions (LCIs) in the pinealocytes, and extensive accumulations of presumptive secretion in the extracellular compartment, suggesting an enhanced secretory activity. In the dry season with average monthly rainfall of 13 mm (light phase of 11 h, and temperature of 19°C), however, the pinealocytes were characterized by the presence of numerous clear spindles, which exhibited acid phosphatase activity; at this time there were few LVFs and LCIs and rare extracellular accumulations, suggesting a declined glandular activity. We conclude that the cellular activity of the pineal gland in R. losea, living under tropical climatic conditions, is synchronized with the annual changes of rainfall, which is apparently more important than the annual changes of photoperiod and temperature.
Neonatal Melatonin Administration Advances Rat Vaginal Opening and Disrupts Estrous Cyclicity and Estrogen‐Dependent Regulatory Mechanisms of Luteinizing Hormone and Prolactin
Authors: Agrasal MA. VillanúC. , Esquifino A.I.
Published: February 2007

Melatonin (100 μrat) was administered to female rats on day 5 of life, 3 hours prior to the onset of darkness or at 12:00 hours. Melatonin administration induced precocious puberty in both cases, as indicated by the advance of the time of the vaginal opening and the appearance of the first estrous smear as compared with controls (P < 0.01), together with an increase in the number of estrous smears (P < 0.05) and a reduction in the number of thestrous smears (P < 0.05). Decreased serum prolactin levels were observed on day 21 of age (P < 0.05) in melatonin‐treated rats with both of the melatonin injection times as compared with controls. No differences were apparent in basal luteinizing hormone (LH) levels either at 30 or at 60 days of age comparing melatonin‐ and vehicle‐treated rats with either of the scheduled melatonin injection times. As to serum follicle‐stimulating levels (FSH) levels, there was a marked decrease in circulating FSH levels in melatonin‐treated rats in both cases on days 21, 30, and 45 (P < 0.05) as compared with controls. A marked increase of serum prolactin at both 48 and 55 hours after estradiol benzoate (EB) administration was detected in 30‐day‐old melatonin‐treated rats as compared with controls (P < 0.05 for both points). Also, an increased responsiveness of prolactin to EB was found on the first day post‐administration. At 60 days of age, an increase in prolactin responses to EB was observed on the first day post‐administration (31 and 48 hours after, (P < 0.01), whereas no differences were detected at any other stuthed time. The LH burst that occurs 31 hours after EB administration in 30‐day‐old rats was decreased in melatonin‐treated animals as compared with controls (P < 0.05). In 60‐day‐old melatonin‐treated rats, a marked increase in the LH response to EB administration, 31 hours after injection (P < 0.01), was observed. These data suggest that neonatal melatonin administration in pharmacological amounts induces precocious puberty as measured by vaginal opening and, furthermore, it advances the appearance of the first estrous smear with age‐dependent modifications of estrous cyclicity and prolactin and LH responses to EB.
Evidence for Dual Adrenergic Receptor Regulation of Ovine Pineal Function
Authors: Morgan P.J. , Davidson G.R. , Lawson W.
Published: February 2007

Both α1‐ and β‐adrenergic receptors are present on ovine pineals. In the rat these two receptors interact so that activation of the α1‐receptor potentiates the β‐receptor‐mediated changes in cyclic AMP and the correlated changes in pineal N‐acetyltrans‐ferase (EC 2.3.1.87). Here we investigate possible interactions between α1‐ and β‐receptors through changes in cyclic AMP and assess the importance of each receptor to the melatonin response in ovine pineal punches/slices in vitro. The adrenergic agonists isoproterenol (ISO), noradrenaline (NA), and phenylephrine (PHE) stimulated dose‐dependent changes in cyclic AMP with the order of potency of ISO>NA>PHE, consistent with their relative binding affinities for the β‐receptor. The β‐receptor antagonist, propranolol, showed dose‐dependent inhibition of the ISO effect, whereas the α1‐selective antagonist, prazosin, had no effect. The S‐shape of the stimulation and inhibition curves for ISO reflects cyclic AMP changes mediated by the β‐receptor only without interaction through the α1‐receptor. Each of the adrenergic agonists stimulated indistinguishable dose‐dependent increases in melatonin release. The ability of PHE to stimulate changes in melatonin release in the absence of concomitant changes in cyclic AMP indicates an important role for the α1‐receptor. Prazosin inhibits this response, substantiating this conclusion. However, as propranolol is also inhibitory, it seems that the a 1‐receptor response is absolutely dependent upon a small level of β‐receptor stimulation, thus providing evidence for adrenergic receptor interaction at a step other than cyclic AMP.
Sensitivity of Goats to a Light Pulse During the Night as Assessed by Suppression of Melatonin Concentrations in the Plasma
Authors: Deveson Sharon L. , Arendt Jospehine , Forsyth Isabel A.
Published: February 2007

This study investigates the ability of a 1 h light pulse of different intensities at night to suppress plasma melatonin in goats. Six female Saanen dairy goats, about 2 yr old, were housed in a light‐tight shed. The goats were habituated for 1 wk to an 8L: 16D photoperiod (40.70 ± 4.16 μW/cm2; 137 ± 14 lux), lights on 0800 h. A 1 h light pulse, of different intensity on each occasion, was given from 1900 to 2000 h. Light intensity was measured by using a lux meter (mean of 36 measurements at goat's eye level). Five different light intensities were given during December in the order 4.22 ± 0.62 μW/cm2 (14.2 ± 2.1 lux), 0.68 ± 0.09 μW/cm2 (2.3 ± 0.3 lux), 0.26 ± 0.004 μW/cm2 (O.87 ± 0.14 lux), darkness, 40.70 ± 4.16 μW/cm2 (137 ± 14 lux), with 1–3 d between treatments. The goats were bled hourly from 1500 to 1900 h and every 15 min from 1900 to 2100 h, and a last bleed occurred at 2200 h. Dark‐phase samples were taken in dim red light (<0.03 μW/cm2; 0.1 lux). Plasma was assayed for melatonin by radioimmunoassay. Suppression of melatonin concentrations increased as light intensity increased as follows: Darkness, 0%; 0.26 ± 0.004 μW/cm2; 0%; 0.68 ± 0.09 μW/cm2; 43.1%; 4.22 ± 0.62 μW/cm2, 71.1%; 40.70 ± 4.16 μW/cm2, 81.2%. Suppression was significant (P<0.05) at light intensities >0.68 μW/cm2, 2.3 lux. A hyperbolic relationship existed between percent suppression and light intensities.
Daily Melatonin Injections Have Only Minor Effects on Gonadotropins of Intact or Castrated Male Rats Kept Under Constant or Periodic Light
Authors: Porkka‐Heiskanen T. , Laakso M. L. , Stenberg D. , Johansson G.
Published: February 2007

Daily Melatonin Injections Have Only Minor Effects on Gonadotropins of Intact or Castrated Male Rats Kept Under Constant or Periodic Light

Intact and castrated adult male Wistar rats were kept under constant or periodic (lights on 0600 and off 1800 h) light for 1 wk. During the study they received melatonin or saline injections daily either at 0900 or 1600 h. After each experiment, serum samples and the adenohypophyses were collected between 1000 and 1100 h and the gonadotropin concentrations were measured radioimmunologically. We had previously found changes in light sensitivity of the hypothalamo‐pituitary axis of castrated rats and hypothesized that this axis could also involve changes in sensitivity to exogenous melatonin. However, the results of the present study do not support the hypothesis.
Effects of Short‐Day Photoperiods and of N‐(2,4‐Dinitrophenyl)‐5‐Methoxytryptamine, a Putative Melatonin Antagonist, on Melatonin Synthesis in the Harderian Gland of the Syrian Hamster, Mesocricetus auratus
Authors: Buzzell Gerald R. , Menendez‐Pelaez Armando , Troiani Maureen E. , McNeill M. Evelyn , Reiter Russel J.
Published: February 2007

The Harderian glands of Syrian hamsters contain melatonin and the enzymes N‐acetyltransferase (NAT) and hydroxyindole‐O‐methyltransferase (HIOMT) which synthesize melatonin from serotonin. Because the Harderian glands share this metabolic pathway with the pineal gland, we examined the effects of short‐day photoperiods, which stimulate pineal‐mediated gonadal regression, and N‐(2,4‐dinitrophenyl)‐5‐methoxytryptamine (ML‐23), which has been described as a melatonin antagonist, on melatonin synthesis in the Harderian glands of the hamster.

Harderian glands of male hamsters kept in short days had reduced NAT activity and melatonin concentration, but HIOMT activity was unchanged from that of longday controls. In males kept in short days, ML‐23 restored melatonin concentrations to levels seen in long days but did not affect the short‐day induced reduction in NAT activity. ML‐23 had no effect upon NAT or HIOMT activity or melatonin concentration in male hamsters kept on long days.

Harderian glands of female hamsters kept on short days had reduced melatonin concentrations, but NAT and HIOMT activities similar to those of long‐day controls. ML‐23 had no effect on Harderian NAT or HIOMT activities or melatonin concentration in females kept in short days. However, in females kept in long days, ML‐23 treatment led to increased NAT activity and decreased melatonin concentrations.

We conclude from these results that short‐day photoperiods alter some aspects of melatonin synthesis in hamster Harderian glands and that these effects differ in males and females. ML‐23 does not usually prevent the effects of short days on Harderian melatonin synthesis, suggesting that it is not a melatonin antagonist in the Syrian hamster.
Postnatal Development of the Dog Pineal Gland: Electron Microscopy
Authors: Calvo J. , Boya J. , García‐Mauriño J. E. , Lopez‐Carbonell A.
Published: February 2007

The ultrastructure of the dog pineal gland from the first postnatal day to the seventh month is described. In the first postnatal stages, pineal parenchyma only shows immature proliferative cells with abundant cytoplasmic glycogen. Nerve fibers are seen in the pineal connective tissue spaces. The differentiation of the dog pineal cell types begins in the first postnatal week. Both pinealocytes and pigmented cells are first seen on the fourth postnatal day. The pineal astrocytes are observed on the tenth day. Immature cells are still found in the pineal gland of 1 mo‐old dogs. The differentiation of the dog pineal cell types is completed by the second postnatal month.