Brief report: melatonin-related hypogonadotropic hypogonadism.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R J Reiter
Publications and source records attributed to R J Reiter.
Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism.
In-vitro rat pineal glands stimulated with the beta-adrenergic receptor agonist isoproterenol to induce melatonin synthesis and exposed for 1 h to a pulsed 0.4-G static magnetic field demonstrated significant inhibition of serotonin-N-acetyltransferase activity and melatonin content. 2-h exposure to pulsed magnetic field also resulted in a significant reduction in isoproterenol-induced serotonin-N-acetyltransferase activity. These results support the idea that the cultured pineal gland can be affected directly by artificially generated weak magnetic fields.
Animals↗
Morphofunctional aspects of the mammalian pineal gland.
The primary aim of this review is to present the current state of knowledge of the ultrastructure of the mammalian pineal gland, with emphasis on its functional aspects. Basic ultrastructural features of the mammalian pinealocytes are presented with special attention paid to ultrastructural aspects of pineal secretion.
Animals↗
The ageing pineal gland and its physiological consequences.
Melatonin, the chief hormone of the pineal gland, is produced and secreted into the blood in a circadian manner with maximal production always occurring during the dark phase of the light:dark cycle. Whereas the 24h rhythm of melatonin production is very robust in young animals including humans, the cycle deteriorates during ageing. The rhythm of melatonin can be substantially preserved during ageing by restricting the food intake of experimental animals; this same treatment increases the life span of the animals. The exogenous administration of melatonin to non-food restricted animals also reportedly increases their survival. Moreover, melatonin has been shown to have immunoenhancing effects and oncostatic properties. The implication of these studies is that melatonin may have both direct and indirect beneficial effects in delaying ageing processes or it may retard the development of processes (e.g., immunodeficiency and tumor growth) which contribute to a reduced life span.
Aging↗
Iodothyronine 5'-deiodinating activity in the pineal gland.
1. The presence of an iodothyronine 5'-deiodinating activity has been described in the pineal gland of various rodents, and it has been identified as a type II 5'-deiodinase isoenzyme since it is relatively insensitive to inhibition by propylthiouracil and its activity increases during hypothyroidism. 2. 5'-Deiodinase activity in the rat pineal gland follows a nyctohemeral profile, exhibiting basal values during the day and maximal values at night. The nocturnal increase is dependent on the noradrenergic input from the superior cervical ganglia, and both in vivo and in vitro studies show that beta-adrenergic receptors are primarily involved in the activation of the enzyme. 3. Day-night differences in rat pineal 5'-deiodinase activity are found beginning at 2 weeks of age, with rhythms increasing in amplitude until maximal differences are reached in adult animals. During the maturation of the rhythm, changes in regulation of enzyme activation are observed. Thus, during the first 2-3 weeks of age, alpha-adrenergic receptors appear to be as important as beta-adrenergic receptors in regulating the deiodinating activity of the pineal. However, in adults, no role of alpha-adrenergic receptors has been described. 4. Although regulation of 5'-deiodinase activity in the pineal gland is well established, few data are available concerning the physiological significance of the enzyme in the gland. Of the studies that have been performed, those attempting to demonstrate a relationship between pineal 5'-deiodinase activity and other pineal rhythms, e.g. those of melatonin production and N-acetyltransferase activity, indicates that the latter rhythms do not rely on the cyclic production of T3. The alternate possibility that the 5'D rhythm depends on the cyclic production of melatonin remains to be examined.
Animals↗
Age and food restriction alter the porphyrin concentration and mRNA levels for 5-aminolevulinate synthase in rat Harderian gland.
The effects of age and food restriction on the porphyrin concentration in Harderian glands were studied in male Fisher 344 rats. Harderian gland porphyrin concentrations increased with age; this was statistically significant in 20 month old animals compared with 3 month old animals. Food restriction (by 40%) prevented the age-associated rise in porphyrins; thus, in 20 month old food restricted rats had porphyrin concentrations similar to those found in young animals. In a second experiment, we correlated the age-associated rise in Harderian gland porphyrin concentrations with an increase in mRNA levels for 5-aminolevulinate synthase (ALV-S). Both the porphyrin concentration and ALV-S mRNA rose at 12 and 18 months of age, but decreased by 24 months of age. It is concluded that, a) porphyrin biosynthesis in the Harderian glands increases up to 20 months of age but decreases in rats that are 24 months old, and b) food restriction prevents the porphyrin rise associated with age in the Harderian gland of male Fisher 344 rats.
5-Aminolevulinate Synthetase↗
Testosterone sensitive dihydropyridine binding in the Harderian gland of the male hamster.
It is well known that in different tissues, dihydropyridines bind at nanomolar concentrations to a receptor and block voltage-operated Ca2+ channels. In studies reported here, Harderian gland tissue homogenates from intact male hamsters exhibited significant dihydropyridine binding (Bmax = 1700 fmoles/mg protein) of high affinity (Kd = 1.1 nM). Tissue homogenates from female animals exhibited a similar Kd value (1.35 nM) but receptor density per mg protein was significantly reduced (Bmax = 270 fmoles). Dihydropyridine binding of Harderian gland tissue homogenates from castrated males was reduced greater than 80% (Bmax = 225 fmoles/mg protein). Treatment of castrated males with subcutaneous testosterone pellets resulted in significant restoration of dihydropyridine binding activity (approximately 80%, Bmax = 1630 fmoles/mg protein) with a comparable binding constant (Kd = 1.50 nM) as observed for noncastrated, control animals. Addition of testosterone (ex vivo) to homogenates from castrated hamsters did not restore dihydropyridine binding to control levels. These data indicate: (a) the Harderian gland from male hamsters exhibits significant dihydropyridine binding; (b) ligand binding is abolished following castration; and (c) significant restoration of dihydropyridine binding occurs following in vivo testosterone treatment. The dependence of dihydropyridine binding restoration upon in vivo steroid hormone administration suggests probable involvement of the steroid at the transcriptional level although non-genomic mechanisms such as the binding of testosterone to a receptor resident in the plasma membrane and subsequent activation of Ca2+ channels can not be ruled out.
Animals↗
Alterations of the circadian melatonin rhythm by the electromagnetic spectrum: a study in environmental toxicology.
The nightly production and secretion of melatonin by the pineal gland, an endocrine organ near the anatomical center of the brain, provides important time-of-day and time-of-year information to the remainder of the body. In mammals, the circadian rhythm of melatonin (low levels during the day and high levels at night) is synchronized by the prevailing light:dark environment with the retinas of the eyes doing the photoreception required for the induction of this rhythm. The advent of artificial light sources has allowed animals or humans to be exposed to light at unusual times, i.e., during the night. Light falling on the retinas at night leads to a rapid depression in the production and secretion of melatonin by the pineal gland. The magnitude of the drop in circulating melatonin due to light exposure at night is related to the brightness (intensity) as well as the wavelength (color) of light to which humans are exposed. The lowered melatonin values following unusual light exposure at night provide erroneous information to a number of organs that respond to the melatonin message since the signal implies it is day when, in fact, it is still night. Besides visible light, certain ultraviolet wavelengths as well as extremely low frequency electric and magnetic fields may also disturb the melatonin rhythm. These nonvisible wavelengths may influence the circadian melatonin rhythm by mechanisms similar to those by which light causes disturbances of melatonin production and release.
Animals↗
Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics.
The 24-h profiles of plasma melatonin and cortisol were evaluated in 7 drug-free male paranoid schizophrenics and in 7 healthy subjects matched to the patients for age, sex, body weight, height and season of testing. Blood samples were obtained at 20.00, 22.00, 24.00, 01.00, 02.00, 06.00, 08.00 and 12.00 h. Light was turned off from 21.00 to 07.00 h. Compared with that of the normal controls, the circadian rhythm of plasma melatonin was absent in paranoid schizophrenics (F7.84 = 7.30, p less than 0.0001; two-way ANOVA with repeated measures) whereas the 24-h profile of plasma cortisol was preserved, although at a slightly higher level (F1.12 = 26.810, p less than 0.0002). The melatonin/cortisol ratio was significantly higher in healthy subjects than in the schizophrenic patients. A functional relationship between disturbances in the melatonin rhythm especially and schizophrenia may be proposed, although the significance of this relationship remains to be elucidated.
Adult↗
Breast cancer, blindness and melatonin.
The hypothesis is advanced that blindness from an early age may lead to a reduced risk of breast cancer through altered patterns of melatonin secretion by the pineal gland. The available experimental evidence in animals and in vitro is consistent with this hypothesis. The hypothesis can be tested in humans by a simple observational study in which the breast cancer risk in blind women is compared with that of all women. The effect of age at onset, duration and degree of blindness could also be assessed, after adjustment for known risk factors for breast cancer. Melatonin might prove to be a natural oncostatic agent of practical value in cancer prevention.
Blindness↗
A brief survey of pineal gland-immune system interrelationships.
The present paper summarizes evidence that support the hypothesis of the existence of bilateral interactions between pineal gland and the immune system. Both in vivo and in vitro experiments show that the pineal gland, via its hormone melatonin, enhances immune function. Mechanisms involved in this immunostimulatory effect are not well understood, but some evidence suggests the existence of specific binding sites for melatonin on immune cells. Moreover, the release of opioid peptides and interleukin-2 by T-helper cells may also participate in this mechanism by activating, at least natural killer activity and antibody-dependent cellular cytotoxicity. Some immune signals, i.e., gamma-interferon, may be involved in regulating pineal function, thereby representing a regulatory mechanism in the opposite direction. The physiological and clinical significance of these data remains to be studied.
Animals↗
Magnetic field effects on pineal indoleamine metabolism and possible biological consequences.
In recent years, there has been a great deal of publicity concerning the possible health effects of electric and/or magnetic field exposure. One of the most frequently reported observations after the exposure of animals to either electric or magnetic fields relates to alterations in the metabolism of serotonin (5HT) to melatonin within the pineal gland. This review summarizes these results particularly in animals exposed to intermittently inverted, non-time varying magnetic fields, i.e., pulsed static magnetic fields. When exposure occurs at night, the conversation of 5HT to melatonin is typically depressed, not unlike that after light exposure at night. The mechanisms by which pulsed magnetic fields alter the ability of the pineal to convert 5HT to the chief pineal hormone melatonin remains unknown but may involve effects on any or all of the following: the retinas, the suprachiasmatic nuclei, the peripheral sympathetic nervous system, and the pinealocytes. Results to date suggest that induced electrical currents (eddy currents) produced by the pulsed magnetic fields are particularly detrimental to pineal indoleamine metabolism and may be an important causative factor in the metabolic changes measured. The physiological consequences of perturbations in the melatonin rhythm induced by magnetic field exposure remain unknown.
Animals↗
Vasoactive intestinal peptide stimulates N-acetyltransferase and hydroxyindole-O-methyltransferase activities and melatonin production in cultured rat but not in Syrian hamster pineal glands.
The purpose of this study was to compare the responses of the Syrian hamster and rat pineal glands in organ culture to vasoactive intestinal peptide (VIP). The endpoints in these studies were the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as pineal and medium melatonin levels. When rat pineal glands were incubated with either VIP (1 microM) or isoproterenol (1 microM), a beta-adrenergic agonist, a significant increase in NAT and HIOMT activities and melatonin levels were observed within 3 hr. Conversely, during the day, VIP (1 microM) was ineffective in stimulating these parameters in hamster pineal gland after incubation times of either 2, 4, 6, or 8 hr. In another experiment, hamster pineal glands were collected from animals killed in the late dark period (after 30 min light exposure). In these glands, isoproterenol promoted NAT activity and melatonin production; however, VIP was ineffective in stimulating either NAT or HIOMT activities; likewise, VIP had no stimulatory effect on pineal melatonin levels at night. Finally, when hamster pineal glands at night were incubated with either 0, 10 nM, 100 nM, 10 microM, or 100 microM VIP, no changes in any parameter of melatonin synthesis were measured. The results indicate that the hamster pineal gland, unlike that of the rat, may not respond to VIP with an increased melatonin production.
Acetylserotonin O-Methyltransferase↗
Adrenergic regulation of type II 5'-deiodinase circadian rhythm in rat harderian gland.
This paper reports on the regulation of the nyctohemeral profile of type II thyroxine 5'-deiodinase (T45'D) activity in the rat harderian gland. Harderian gland T45'D activity exhibits a nighttime increase with maximal values late in the dark period (0200-0400 h) and basal values during the daytime. The nocturnal rise of the deiodinating activity was prevented by either exposure of animals to light at night, injecting the animals with both alpha- and beta-adrenergic receptor blockers, or bilateral superior cervical ganglionectomy (SCGx). However, adrenalectomy did not affet the enzyme activity in the harderian gland. In brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1-adrenergic stimulation by blood-circulating catecholamines, adrenalectomy significantly decreased T45'D activity. Deiodinating activities in brain frontal cortex (BFC) and pituitary gland were unaffected by adrenalectomy. Unlike in the harderian gland, SCGx did not modify the T45'D activity in either BAT, BFC, or the pituitary gland. The results suggest that elevated plasma catecholamines are not required for harderian gland T45'D activation and that the nyctohemeral profile of the enzyme activity in the harderian gland is dependent on the noradrenergic input from the superior cervical ganglia.
Adrenalectomy↗
Beta-adrenergic and peptide N-terminal histidine and C-terminal isoleucine stimulation of N-acetyl-transferase activity and melatonin production in the cultured rat pineal gland.
The purpose of this investigation was to compare the effect of peptide N-terminal histidine and C-terminal isoleucine (PHI) with that of the beta-adrenergic agonist isoproterenol (ISO) on N-acetyltransferase (NAT) activity and melatonin production in the cultured rat pineal gland. Pineal glands were removed and placed in organ culture containing PHI, ISO, or PHI plus ISO at different dosages, and subsequent changes in NAT activity and melatonin levels were measured. PHI stimulated these parameters in both a time- and dose-dependent manner. Combined treatment with PHI (10(-6) M) and high doses of ISO (either 10(-7) or 10(-8) M) did not potentiate the effect of the peptide in terms of either NAT activity or melatonin levels in the pineal gland. However, at a lower concentration, ISO (10(-9) M) had additive effects to those of PHI in both cultured pineals and medium. The results suggest that PHI modulates melatonin synthesis in the rat pineal gland. Furthermore, stimulation of the pineal with both PHI and ISO demonstrates an additive effect rather than a synergistic action of these compounds. It is presumed that ISO and PHI stimulate pineal melatonin production via separate receptors, but they probably use the same intracellular second messenger, cAMP, to do so. This is the first study showing an effect of the peptide PHI on pineal melatonin production in any vertebrate.
Acetyltransferases↗
Remembrance: growing up with the pineal gland: early recollections.
Explore the source record for details and available documents.
Animals↗
Hypophysectomy prevents the castration-induced increase in porphyrin concentrations in the harderian glands of the male golden hamster: a possible role for prolactin.
The Harderian glands of golden hamsters contain high concentrations of porphyrin pigments, with female hamsters having considerably higher porphyrin concentrations than males. Castration of male hamsters leads to a rapid increase in porphyrin concentrations; testosterone treatment of females has the opposite effect, suggesting a central role for androgens in inhibiting the realization of high porphyrin concentrations by this organ. Previous studies in our laboratories have shown, however, that administration of a dopamine agonist to castrated hamsters prevents the normal increase in Harderian porphyrins from occurring. This suggests that prolactin is necessary for low androgen levels to lead to maximal increases in Harderian porphyrin concentrations. The present study tested the hypothesis that prolactin is involved in the control of Harderian porphyrin levels in the golden hamster. Although hypophysectomy of male hamsters reduced serum testosterone to levels in castrated hamsters, the resultant increase in Harderian porphyrin concentrations was much less than that seen after a similar period of castration. Furthermore, combining the two procedures (castration and hypophysectomy) also led to a blunted increase in Harderian porphyrin, suggesting that a pituitary hormone is necessary for low testosterone levels to lead to increased porphyrins. Evidence that this pituitary hormone is prolactin comes from the observations that eliminating all pituitary hormones except prolactin, by severing the connection of the pituitary with the hypothalamus or transplanting the pituitary to a distant site (beneath the kidney capsule) led to greatly augmented Harderian porphyrin levels, in intact or castrated male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
N-methyl-D-aspartate does not prevent effects of melatonin on the reproductive and thyroid axes of male Syrian hamsters.
The reproductive and thyroid status of male Syrian hamsters maintained on long days (14 h light, 10 h darkness) were assessed after 10 weeks of daily injections of pharmacological doses of melatonin (25 micrograms s.c.) and/or N-methyl-DL-aspartic acid (NMDA, 0.025-6 mg i.p.), a compound with receptor sites in the central nervous system which are known to affect reproduction. Melatonin given during the late light phase decreased reproductive organ weights and levels of serum and pituitary prolactin and serum thyroxine (T4); these results are similar to published reports on the effects of chronic short photoperiod treatment of this species. Reproductive organ weights, T4 levels and values for prolactin did not differ significantly between groups receiving only melatonin and those receiving NMDA in addition to melatonin; likewise these variables did not differ significantly between groups receiving only either NMDA or saline. NMDA alone and in combination with melatonin increased serum tri-iodothyronine (T3). The brown adipose tissue enzyme T4 5'-deiodinase demonstrated an increased activity in the presence of NMDA, with the lowest dosage eliciting the most significant effect. Previous studies have demonstrated that NMDA reverses the reproductive effects of short photoperiod. The results of this study show that NMDA is incapable of preventing the inhibitory reproductive effects of exogenously administered melatonin. These observations are consistent with the proposal for a site of action for NMDA on neural regions more proximal than those altered by melatonin; alternatively, NMDA may interfere with neurotransmitter actions in the pathway controlling melatonin production.
Animals↗