Showing papers in "Journal of Pineal Research in 1988"
TL;DR: Chromatographic analysis indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C‐MT, which was found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb‐pons.
Abstract: The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutesmore » later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites.« less
85 citations
TL;DR: Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady‐state entrainment, and the time of day of melatonin administration appears to be a critical factor in its mode of action.
Abstract: Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at the new dark onset reentrained by a phase delay of the activity rhythm. The remaining nine melatonin-injected rats and 14 of the 15 control injected rats phase advanced. Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady-state entrainment. In contrast, the effects of melatonin injections given at the end of both the old and new dark periods are difficult to interpret due to the effects of the injection procedure itself at these times. Following an 8-h advance of the LD cycle, all melatonin-injected rats phase advanced while all vehicle and uninjected control rats phase delayed when injections were given at the old dark onset. As has been found in other research areas, the time of day of melatonin administration appears to be a critical factor in its mode of action. It is yet to be established whether these results from the use of pharmacological doses of melatonin are indicative of endogenous melatonin's involvement in the circadian reentrainment mechanism.
64 citations
TL;DR: The results show that pineal output barely changes during childhood and adolescence, but there is an age related decrease in SaMT excretion/unit body mass which correlates with an age‐related increase in body mass.
Abstract: Twenty-four-h urine samples, divided into two fractions representing night- and daytime melatonin production, were collected from 115 healthy individuals between the ages of 3 and 80, of known height and weight, and assayed for 6-hydroxy melatonin sulphate (SaMT), a major urinary metabolite of melatonin, by gas chromatography mass spectrometry. The population was divided for analytical purposes into children (boys aged 3-10.99, girls aged 3-9.59), adolescents (males aged 11-17.99, females aged 9.60-17.99), and adults (men and women over 18). The results showed approximately the same excretion over 24 h in all 3 groups but that the night/day ratio was considerably greater in children and adolescents compared to adults (P less than 0.001). However, when the results were expressed as a function of body weight (BW), body surface area (BSA), or creatinine excretion (CE), nocturnal SaMT was higher in children than in adults (P less than 0.001 for all 3 parameters) or adolescents (BW, P less than 0.001; BSA, P less than 0.002; CE, P less than 0.001) and was higher in adolescents than in adults (BW and BSA, P less than 0.001). Children also excreted more during the day than adults (BW, P less than 0.01; CE, P less than 0.001) or adolescents (BW alpha CE, P less than 0.02). Our results show that pineal output barely changes during childhood and adolescence. However, there is an age related decrease in SaMT excretion/unit body mass which correlates with an age-related increase in body mass. We therefore conclude that the decrease in circulating levels of melatonin during growth and sexual maturation is brought about by an increase in body mass.
63 citations
TL;DR: The data suggest that MTN inhibited 17α‐hydroxylase, 17–20 desmolase, and 17‐ketoreductase while MEL, MTOL, MIAA, and HIAA inhibited only 17‐20 des molase, which was reflected in its greatest inhibition of testosterone production.
Abstract: The inhibition elicited by pineal indoles on testosterone production by isolated rat Leydig cells could not be overcome by a maximally active dose of luteinizing hormone (LH), and dibutyryl-cAMP-induced steroidogenesis was also suppressed, suggesting that the indoles did not exert their effect through an interaction with LH receptors on Leydig cells. Pregnenolone-induced progesterone secretion was unaffected, indicating that the activity of 3 beta-dehydrogenase was not altered. Methoxytryptamine (MTN) at a dose of 1 mM decreased progesterone-induced 17 alpha-hydroxyprogesterone secretion by 50%, suggesting that the enzyme 17 alpha-hydroxylase was inhibited. The inhibition caused by other pineal indoles was either very slight or absent. MTN reduced 17 alpha-hydroxyprogesterone-induced androstenedione production by 65%, methoxytryptophol (MTOL) and melatonin (MEL) by 35%, and methoxyindoleacetic acid (MIAA) and hydroxyindoleacetic acid (HIAA) by 10%, revealing an inhibition of 17-20 desmolase. The reduction of androstenedione-induced testosterone production by MTN infers inhibition of 17-ketoreductase activity. However, testosterone production induced by either dehydroepiandrosterone or androstenedione was unaffected by other indoles. The data suggest that MTN inhibited 17 alpha-hydroxylase, 17-20 desmolase, and 17-ketoreductase while MEL, MTOL, MIAA, and HIAA inhibited only 17-20 desmolase. The highest potency of MTN in inhibiting enzymes on the testosterone biosynthestic pathway was reflected in its greatest inhibition of testosterone production. On the other hand, MIAA and HIAA had the lowest potency in inhibiting the enzymes and testosterone production while MEL and MTOL had intermediate potencies.
51 citations
TL;DR: The hypothesis that the opioidergic system, in certain circumstances, might contribute to the activation of melatonin secretion is supported.
Abstract: 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 hydrochloride 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 radioimmunoassay (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.
48 citations
TL;DR: Plasma melatonin was determined in samples of patients with colorectal carcinoma and in controls using an iodinated radioimmunoassay and during the night, melatonin concentration in cancer patients was significantly lower than in controls.
Abstract: 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
47 citations
TL;DR: It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.
Abstract: 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 0400 h (P less than 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.
44 citations
TL;DR: Evidence is provided for melatonin controlling the nocturnal increase of prolactin via its ability to stimulate prolactIn release and oral administration of 6 mg melatonin significantly stimulated prolact in release above concentrations measured after placebo administration in both the morning and evening time periods.
Abstract: The relationship between the concentrations of melatonin and prolactin over the 24-h cycle has been investigated in a group of young men at three times in the year. Melatonin and prolactin showed a significant positive correlation (P less than 0.001) for all times during the 24-h period but with a greater contribution from concentrations during the nocturnal period, when both hormones were elevated. The positive correlation for nocturnal concentrations was evident in February and March (P less than 0.01) but was of greatest significance in June (P less than 0.001). In blood samples taken at 15-min intervals during the morning (0800-1200) and evening (2000-2400), melatonin and prolactin concentrations were not significantly correlated. Melatonin concentrations increased before prolactin during the evening and decreased before prolactin in the morning. Oral administration of 6 mg melatonin significantly stimulated prolactin release above concentrations measured after placebo administration, in both the morning (P less than 0.05) and evening (P less than 0.01) time periods; the prolactin response being greater in the evening. These results provide evidence for melatonin controlling the nocturnal increase of prolactin via its ability to stimulate prolactin release.
43 citations
TL;DR: In a small sampling at necropsy, a statistically significant (P < .005; determined morphometrically) reduction in the anatomic size of the pineal gland in SIDS infants, as compared to age‐matched controls.
Abstract: Sudden infant death syndrome (SIDS) affects infants between 1 month and 1 yr of age, has no known cause, and is diagnosed by exclusion of all other causes of death. The primary mechanism of death in SIDS is considered to be irreversible respiratory cessation during sleep. In a small sampling at necropsy we have observed a statistically significant (P less than .005; determined morphometrically) reduction in the anatomic size of the pineal gland in SIDS infants, as compared to age-matched controls. Whether correspondingly altered pineal glandular function is present in SIDS is as yet unanswered.
41 citations
TL;DR: 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.
Abstract: The effect of two different conditions of humidity (80 +/- 5% and 40 +/- 5%) under stimulatory photoperiod (14L/10D) and high temperature (38 +/- 2 degrees 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 humidity information to control the male gonadal function in the Indian palm squirrel, Funambulus pennanti.
30 citations
TL;DR: A clear dose‐response relationship was apparent between light intensity and degree of melatonin suppression, and plasma melatonin measurements indicated that secretion was significantly suppressed.
Abstract: The intensity of cool, white, fluorescent light required to suppress melatonin secretion in Ile-de-France rams was investigated. Animals were conditioned to 12L:12D, lights on 0600 hours, 104 microW/cm2 (350 lux) at eye level and subjected to a 1-hour light pulse beginning 3 hours after lights off. Plasma melatonin measurements indicated that secretion was significantly suppressed by 0.30, 7.46, and 26.32 microW/cm2 (1.02, 25.10, and 88.60 lux, respectively) but not by 0.043 microW/cm2 (0.15 lux). A clear dose-response relationship was apparent between light intensity and degree of melatonin suppression.
TL;DR: Although Ca2+ is necessary for α1‐adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phosphate C activity.
Abstract: Activation of alpha 1-adrenergic receptors increases [Ca+2]i and phosphatidylinositol phosphodiesterase (phospholipase C) activity in the pinealocyte. In this report the receptor involved in the stimulation of phospholipase C activity was further characterized, and the role of Ca2+ in this effect was investigated in some detail. Phospholipase C activity was estimated by measuring the production of [3H]inositol phosphates by [3H]inositol-labelled dispersed pinealocytes in suspension culture. Norepinephrine stimulated [3H]inositol monophosphate production severalfold; this was blocked by alpha 1-adrenergic antagonists, including prazosin, WB 4101, and phenoxybenzamine, but by neither an alpha 2- nor a beta-adrenergic antagonist, confirming that an alpha 1-adrenoceptor is involved in the regulation of phosphatidylinositol hydrolysis. Treatment with the Ca2+ chelator, EGTA, or with inorganic Ca2+ blockers, including Co2+, Mn2+, and La3+, reduced the norepinephrine-stimulated response, suggesting that the alpha 1-adrenergic stimulation of phospholipase C activity is Ca2+ dependent. However, phospholipase C activity was not increased by elevating intracellular Ca2+ with either the Ca2+ ionophore A23187 or with depolarizing concentrations of K+. These results indicate that although Ca2+ is necessary for alpha 1-adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phospholipase C activity.
TL;DR: Cytodifferentiation of the chick pineal gland throughout the embryonic development was investigated with light and electron microscopy and nuclear invaginations having a large lipid droplet nearby and some aggregations of glycogen are found in the pinealocytes and are transitory changes in structure restricted to certain days of incubation.
Abstract: Cytodifferentiation of the chick pineal gland throughout the embryonic development was investigated with light and electron microscopy. The chick pineal anlage appears first as a small evagination in the diencephalic roof at 60 h of incubation (27–30 somites). Until day 5 of incubation, pineal anlage cells are undifferentiated and appear similar to ventricular ependymal cells. Subsequently, pinealocytes and supporting cells are first distinguishable at 7–8 days, and parafollicular cells are distinguishable at 12 days of incubation. Pigment-containing cells after 6 days and nerve cells after 17 days of incubation gradually increase, especially in the posterior wall of the pineal recess. During embryonic development, the chick pineal gland has both photosen-sory and secretory elements: viz. the former, mitochondria-laden apical protrusions, synaptic ribbons, lamellar whorl-like cilia of the pinealocytes, and adjacent appearance of the pigment-containing cells and the nerve cells; and the latter, dense-cored vesicles of the pinealocytes and dense bodies of the supporting cells. Moreover, nuclear invaginations having a large lipid droplet nearby and some aggregations of glycogen are found in the pinealocytes and are transitory changes in structure restricted to certain days of incubation.
TL;DR: The distribution of nerve fibers containing immunoreactive substance P, estrogen‐ Stimulated neurophysin (ESN), nicotine‐stimulated neuroPhysin (NSN), oxytocin (OT), and vasopressin (VP) was examined in the epithalamic area of adult male and female macaques.
Abstract: The distribution of nerve fibers containing immunoreactive substance P (SP), estrogen-stimulated neurophysin (ESN), nicotine-stimulated neurophysin (NSN), oxytocin (OT), and vasopressin (VP) was examined in the epithalamic area of adult male and female macaques. Perfused or immersion-fixed epithalamic tissues, sectioned, and mounted on glass slides were processed through the avidin–biotin immunofluorescence method.
Fibers containing immunoreactive SP were observed in the pineal organ along the periphery, in the perivascular space, and dispersed between the pinealocytes. Fibers were often observed in the pineal stalk region, and the habenular nuclei had high concentration of immunoreactive SP. Immunoreactive ESN fibers were observed in the stria medullaris, in the lateral habenula, in the pineal stalk, and in the pineal organ. Within the pineal, fibers containing ESN were present in the perivascular space, often concentrated in the walls of blood vessels, but also dispersed between pineal cells. Fibers containing OT, NSN, and VP were also present in the macaque pineal, but in lower quantities compared with fibers containing ESN.
These studies show that the pineal of subhuman primates contain nerve fibers (ESN, NSN, VP, OT) of possibly hypothalamic origin. It also has a rich supply of SP fibers, which might be of habenula origin, peripheral parasympathetic ganglia origin, or both. The functional significance of these peptidergic nerve fibers remains to be determined. However, there are indications that they might be involved in regulation of blood flow and release of secretory products from the pinealocytes.
TL;DR: The presence of type‐II thyroxine 5′‐deiodinase (5′‐D) activity in rat pineal gland and N‐acetyltransferase (NAT) activity, and melatonin content were measured in the same rat Pineal.
Abstract: 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 fmol/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).
TL;DR: The adult dog pineal gland was studied with the electron microscope and two cell types, pinealocytes and astrocytes, could be identified in pineal parenchyma.
Abstract: The adult dog pineal gland was studied with the electron microscope. Pineal connective tissue spaces were poorly developed and showed capillaries with nonfenestrated endothelial cells. Two cell types, pinealocytes and astrocytes, could be identified in pineal parenchyma. Dog pinealocytes showed microtubules, centrioles, occasional cilia, and well-developed Golgi complexes. These cells showed thin processes with bulbous endings packed with vesicles. Astrocytes were characterized by the presence of numerous filaments. Their processes finished forming a glial layer bordering connective tissue spaces. The presence of myelinated and unmyelinated nerve fibers was also described.
TL;DR: Melanophores were studied in tadpoles of the South African clawed toad during the first week after hatching and became punctate in response to a series of melatonin concentrations in their bathing water irrespective of the time of day melatonin was administered.
Abstract: Melanophores were studied in tadpoles of the South African clawed toad, Xenopus laevis, during the first week after hatching (stages 46-49) at 25 degrees C. The tadpoles had melanophores with dispersed melanosomes in the light and punctate melanophores in the dark in LD 12:12. The melanophores remained punctate in constant dark and the melanosomes remained dispersed in constant light. Lights-out (in the light-time of LD 12:12) caused the melanophores to become punctate, which occurred more quickly than the dispersion of melanosomes, which commenced when the lights were turned on (in the dark-time of LD 12:12). Melanophores with dispersed melanosomes in tadpoles (in constant light) became punctate in response to a series of melatonin concentrations (0.2-5 ng/ml) in their bathing water irrespective of the time of day melatonin was administered. An image-analysis technique for assessing melanophore responses was tested.
TL;DR: 5 mg of melatonin was given orally to one subject in a blind experiment and the electrocardiogram (ECG) was recorded together with simple reaction time (SRT) responses over a 5‐h period after taking melatonin.
Abstract: 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.
TL;DR: Daily melatonin injections, which caused gonadal regression in the LSH/SsLak but not in the outbred hamsters, did not simulate the effect of the short photoperiod on the Harderian gland NAT activity and melatonin content of the inbreeding hamsters.
Abstract: The activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) and the melatonin concentration of the Harderian glands of two strains of Syrian hamster females (outbred and inbred LSH/SsLak) exposed to two different photoperiods (14:10 h and 8:16 h) were studied. The Harderian glands of the inbred hamsters showed greater NAT activity than those of the outbred animals. On the other hand, the glands of the outbred hamsters exhibited higher HIOMT activity and melatonin content than those of the inbred LSH/SsLak. Short photoperiod exposure, which produced gonadal regression in the inbred but not in the outbred hamsters, decreased the NAT activity in the inbred animals to the levels of the outbred. HIOMT activity was not affected by the lighting conditions. After the exposure to short days, the melatonin content of the inbred hamster Harderian glands increased to that in the outbred animals. Daily melatonin injections, which caused gonadal regression in the LSH/SsLak but not in the outbred hamsters, did not stimulate the effect of the short photoperiod on the Harderian gland NAT activity and melatonin content of the inbred hamsters.
TL;DR: Pulsations of melatonin levels were found in the confluens sinuum plasma in all the animals studied, suggesting episodic secretion of pineal melatonin in rats, and may provide important insight into the regulation of pulsatile release of neuroendocrine secretions in general.
Abstract: The release patterns of pineal melatonin were studied by continuously monitoring melatonin levels in the confluens sinuum plasma in sighted and bilaterally enucleated rats in the light and dark periods. Plasma melatonin was determined by radioimmunoassay, and the data were analyzed by a computerized algorithm developed in our laboratory. Pulsations of melatonin levels were found in the confluens sinuum plasma in all the animals studied, suggesting episodic secretion of pineal melatonin in rats. Because the minimum melatonin levels in the confluens sinuum were over three times the melatonin levels in the general circulation, it is postulated that 1) there is an episodic release pattern of pineal melatonin superimposed on a basal release pattern and 2) there are two pools of melatonin in the pineal gland, a readily releasible pool responsible for the basal release and a bound pool responsible for the pulsatile release. In the sighted rats, there was no diurnal difference in mean melatonin concentration, mean pulse amplitude, mean pulse rate, mean minimum melatonin level, and mean maximum melatonin level in the confluens sinuum. In the bilaterally enucleated rats, with the exception of the mean pulse amplitude, diurnal rhythms were demonstrated in all the other parameters studied with, higher values in the dark period. This experimental model should be employed in future investigations on the regulation of secretory patterns of pineal melatonin. Results of these studies may provide important insight into the regulation of pulsatile release of neuroendocrine secretions in general.
TL;DR: It is concluded that the neuroendocrine‐reproductive system of the prepubertal F344 female rat is highly sensitive to light deprivation; light deprivation produces its antigonadotrophic effect through the pineal gland; and olfactory bulbectomy does not potentiate the effects of blinding in the F344 rat.
Abstract: 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 inbred 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 less than 0.01) reduction in uterine weight and a 25% (P less than 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.
TL;DR: The consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length.
Abstract: Experiments in minks, as in a number of other seasonal breeders, clearly demonstrate that the pineal gland is essential for the photoperiodic control of reproduction. While maintenance of pineal-intact minks under natural photoperiods results in a set of seasonally appropriate changes in testicular activity, pinealectomized minks undergo none of these changes but rather remain sexually inactive as under long-day conditions. Thus, the consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length.
Although the precise mechanism by which the pineal regulates hypothalamic-pituitary gonadal function remains unknown, the results of the present study indicate that, in the mink, luteinizing hormone-releasing hormone axonal transport is affected by pinealectomy.
Furthermore, our results suggest that the pineal does not act exclusively upon the neuroendocrine-gonadal system but also acts on other functions that are influenced by photoperiod. Pinealectomized minks left in natural conditions cannot adjust their prolactin secretion in response to either long or short photoperiods. Operated animals continued to have plasma prolactin variations but at irregular intervals and with no apparent relation to the time of the year. The data strengthen the hypothesis that melatonin may act at some point on the hypothalamic neuroendocrine systems, which regulate the two functions differently, and that melatonin is not an anti- or progonadal substance but rather a seasonal transducer.
TL;DR: In several animals episodic release of melatonin was apparent, and the episodes were most obvious in the cerebral venous blood at night, but were also apparent in 1 case in the jugular vein plasma and in 1 animal during the day.
Abstract: Blood was collected from the cerebral sinuses and from the jugular vein of 5 ewes during both the day and night. Cerebral sinus samples were collected by means of a permanently indwelling cannula (roughly every 5 min) while jugular vein samples were collected by venipuncture (roughly every 10 min). In each of the 5 animals mean nighttime melatonin concentrations were greater at night than during the day. In 2 animals, cerebral sinus plasma melatonin concentrations were greater than in the jugular vein; in 2 animals the sinus and jugular plasma had similar melatonin levels; in 1 ewe jugular vein blood melatonin levels exceeded those in the cerebral sinus plasma. These differences among animals are presumably due to slight positional differences in the cerebral venous cannula placement. In several animals episodic release of melatonin was apparent. Whereas the episodes were most obvious in the cerebral venous blood at night, they were also apparent in 1 case in the jugular vein plasma and in 1 animal during the day. When episodes appeared they occurred about every 15-20 min.
TL;DR: The results indicate that some aspects of benzodiazepine binding may be influenced by melatonin treatment during the prepubertal period in the rat.
Abstract: The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5more » methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted).« less
TL;DR: Comparisons of the effect of melatonin and 6‐MBOA on testis size in the golden hamster indicate that the consumption ofmelatonin (and presumably melatonin agonists) could serve as an environmental stimulus for reproductive activity.
Abstract: Consumption of young plants containing 6-methoxybenzoxazolinone (6-MBOA) appears to play an important role in the initiation of reproduction each spring in wild populations of the montane vole. Following its identification, 6-MBOA has been found to stimulate the reproductive system in a number of rodent species, but the mechanism of action remains unknown. The chemical structure of 6-MBOA is similar to melatonin, which, in addition to its well-known antigonadal effects, can exert a progonadal influence under certain experimental conditions. To determine if 6-MBOA might act as a melatonin agonist, four experiments were conducted to compare the effect of these two compounds on testis size in the golden hamster, a rodent whose responses to melatonin are well characterized. 1) Hamsters exposed to 14 h light per day (14L:10D) received a daily injection of melatonin (25.0 micrograms) or 6-MBOA (17.8 micrograms). 2) Hamsters exposed to 6L:18D received Silastic capsules (50 or 200 mm) containing melatonin or 6-MBOA. 3) Hamsters exposed to 6L:18D received chow containing melatonin (21.1 or 42.2 micrograms/gm chow) or 6-MBOA (15.0 or 30.0 micrograms/gm). 4) Hamsters exposed to 6L:18D received drinking water containing melatonin (15.5 micrograms/ml) or 6-MBOA (11.0 micrograms/ml). Testis widths were determined at 2--3 week intervals, and after 66-73 days testes were removed and weighed. Melatonin significantly influenced testis size in each experiment, but treatment with 6-MBOA had no effect in any of these experimental paradigms, indicating that 6-MBOA does not act as a melatonin agonist in the hamster. However, these results indicate that the consumption of melatonin (and presumably melatonin agonists) could serve as an environmental stimulus for reproductive activity.
TL;DR: 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.
Abstract: 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.
TL;DR: The fate of 3H‐melatonin after its intracerebroventricular administration was studied both in different brain regions and in subcellular fractions and the rate of disappearance from the brain was found to be multiphasic.
Abstract: 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 (t1/2 = 3.04 min) a slower one (t1/2 = 36 min). We also found a much slower component (t1/2 = 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 KCl 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.
TL;DR: Following pineal removal, melatonin did not augment the pinealectomy‐induced decrease of vasopressin and oxytocin in the neurohypophysis; the hypothalamic storage of both neurohormones was even higher when compared with vehicle‐treated animals.
Abstract: The effect of melatonin on hypothalamic and neurohypophysial vasopressin and oxytocin was investigated in normal and pinealectomized rats. Pinealectomy was followed by a decrease of both vasopressin and oxytocin content in the hypothalamus and neurohypophysis. In unpinealectomized rats, melatonin decreased vasopressin and oxytocin storage in the hypothalamo-neurohypophysial system. Following pineal removal, melatonin did not augment the pinealectomy-induced decrease of vasopressin and oxytocin in the neurohypophysis; the hypothalamic storage of both neurohormones was even higher when compared with vehicle-treated animals.
TL;DR: Catfish subjected to pinealectomy, blinding, or both were exposed to continuous light or continuous darkness during the different phases of the annual reproductive cycle, indicating the involvement of extrapineal and extraocular photoreception in the regulation of reproductive activity in the catfish.
Abstract: To investigate the relative importance of pineal and eyes in ovarian activity, catfish subjected to pinealectomy, blinding, or both were exposed to continuous light (LL) or continuous darkness (DD) during the different phases of the annual reproductive cycle. Pineal or eyes have no influence on ovarian activity during the preparatory, prespawning, and spawning periods of the annual reproductive cycle under these photoregimes. However, the pineal accelerated ovarian activity under LL and DD during the postspawning period. Blinding alone has no effect on ovarian recrudescence under these regimes. However, combined surgery (blinded-pinealectomy) inhibited ovarian development under both these conditions, indicating that the pineal organ is more important than the eyes. Ovarian recrudescence occurred even in the absence of both pineal and eyes, indicating the involvement of extrapineal and extraocular photoreception in the regulation of reproductive activity in the catfish.
TL;DR: In this species the pineal gland during the annual reproductive cycle appears to have either inhibitory, stimulatory, or no effect on gonadal physiology depending upon the sexual conditions.
Abstract: The present study examines the relationship of the pincal gland to gonadal activity during the annual reproductive cycle in the freshwater catfish Clarias batracbus. The hormonal profiles of testosterone, estradiol-17β, estrone, and 17α-hydroxyprogesterone along with the gonadosomatic index (GSI) were monitored to assess the effect of pinealectomy. Pinealectomy appeared to accelerate the gonadal development from January to May. Removal of pineal prior to the start of gonadal recrudescence (January and February), induced initiation of ovarian recrudescence earlier than scheduled in nature. On the other hand pinealectomy during the vitellogenic phase (May to June) reduced the gonadal activity, suggesting the stimulatory role of pineal on gonads. During the remaining period of July to December (postvitellogenic and early resting phase) pinealectomy had no effect on gonadal activity. Thus, in this species the pineal gland during the annual reproductive cycle appears to have either inhibitory, stimulatory, or no effect on gonadal physiology depending upon the sexual conditions.