Seasonal affective disorder and phototherapy.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
L Tamarkin
Publications and source records attributed to L Tamarkin.
Plasma melatonin and the hormone-dependency of human breast cancer.
We studied the 24-hour plasma melatonin profile in three groups of women: normal individuals, women with breast cancer, and women at high risk for breast cancer, to determine the relationship of plasma melatonin to this malignancy. The mean daytime (nadir) and mean nighttime (peak) plasma levels for the normal subjects were 9.1 pg/mL and 70.9 pg/mL, respectively. The mean daytime and nighttime plasma levels, and the range of melatonin day to night differences for women with breast cancer and women at high risk for breast cancer were comparable to each other and to the normal subjects, with no statistically significant differences noted. The patients with breast cancer demonstrated a striking correlation between the melatonin diurnal rhythm and the steroid receptor content of the primary tumor. Women with estrogen (ER) or progesterone (PR) receptor-positive tumors had a significantly lower mean plasma melatonin day to night difference than did patients with ER- or PR-negative tumors. Further, a strong inverse correlation was observed between the plasma melatonin concentration and the quantities of ER and PR in the primary tumor: the lower the plasma melatonin concentration the greater the amount of either receptor in the primary tumor. Plasma melatonin did not correlate with tumor glucocorticoid receptor content or stage of breast cancer among these patients, or with menopausal status, age, parity, or the plasma levels of estrone, estradiol, progesterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH) among all individuals studied. Plasma melatonin was also independent of the degree of risk for breast cancer among the high-risk patients. These findings suggest an important relationship between the plasma melatonin diurnal rhythm and the hormone dependency of human breast cancer, and may have implications for both the prognosis and treatment of this malignancy.
Adolescent↗
Two pools of beta-endorphin-like immunoreactivity in blood: plasma and erythrocytes.
While attempting to delineate the reason for the reported extreme variability of beta-endorphin-like immunoreactivity (beta-ir) in human plasma (eg., nondetectable to 1 ng/ml) by standard radioimmunoassay, we noted that a substantial portion of circulating beta-ir was associated with erythrocytes. That erythrocyte associated beta-ir is authentic beta-endorphin (beta-EP) was confirmed by high performance liquid chromatography (HPLC). Analysis of blood samples from rabbits, rats and mice revealed the presence of beta-ir in erythrocytes from these species as well. These results suggest that there are two pools of beta-endorphin-like immunoreactivity in blood: plasma and erythrocytes.
Animals↗
Plasma melatonin rhythms in euthermic marmots (Marmota flaviventris).
Plasma melatonin concentrations were measured in marmots (Marmota flaviventris) maintained under three short-day (4L:20D; 8L:10D; 10L:14D) and one long-day (14L:10D) photoperiod(s). Each animal had a daily rhythm of plasma melatonin with elevated plasma melatonin levels occurring during the dark period of the lighting cycle. There were no significant differences between any peak values during the night. The mean duration of elevated night melatonin concentrations was significantly different between long-day (16L:8D) and 8L:16D or 4L:20D animals (P less than 0.01). Daytime plasma melatonin levels were not significantly different among the photoperiods. These results characterize plasma melatonin rhythms in a sciurid rodent and demonstrate that this rhythm is modified by photoperiod. Therefore, the plasma melatonin profile could convey information about day length to the animal or, alternatively, the rhythm may be acting as a time-keeping mechanism for other physiological functions.
Animals↗
Plasma melatonin concentrations in hibernating marmots: absence of a plasma melatonin rhythm.
Plasma melatonin concentrations were measured throughout bouts of hibernation in marmots maintained in a short photoperiod (light-dark 8:16) and ambient temperature of 5 or 15 degrees C. Melatonin concentration was also measured in two animals maintained in constant darkness. As an animal entered hibernation, plasma melatonin concentrations dropped to basal levels when body temperature reached 25 degrees C, and they remained low until arousal. During deep hibernation plasma melatonin values did not vary significantly (P greater than 0.05) with respect to time of day or different ambient temperatures. With nocturnal arousal plasma melatonin levels were similar to euthermic night values. Lack of a plasma melatonin rhythm during hibernation suggests that the pineal gland is not temperature compensated during hibernation, and due to the low tissue temperature of the pineal the circadian pacemaker driving melatonin secretion is incapable of stimulating a rhythm.
Animals↗
Regulation of luteinizing hormone release by pulsatile and continuous administration of gonadotropin-releasing hormone to superfused rat and hamster pituitary cells.
Regulation of LH release by GnRH was studied in superfused anterior pituitary cells from 30-day-old female rats or hamsters. Dispersed cells were cultured 4-6 days on Cytodex beads, then loaded into water-jacketed columns, and perfused with medium (0.5 ml/min) at 37 C. Three-minute fractions of effluent were assayed for LH by RIA. LH release was dose related between 10(-10) and 10(-7) M GnRH. Rat and hamster cells released LH at peak rates of 11.3 and 12.5 ng/(min X 10(6) cells), respectively, when first exposed to 10(-8) M GnRH. Short pulses (6 min) of 10(-8) M GnRH given at 30-min intervals had little effect on the rate of LH release by rat pituitary cells; however, if the interpulse interval was reduced to 12 min, release declined 72% by the fifth pulse. In contrast, pulses of 10(-6) M GnRH at 30-min intervals desensitized rat cells. Hamster cells were desensitized by 10(-8) M GnRH after a single pulse regardless of whether a second pulse was given 30 min or 2.5 h later. Similar desensitization also occurred at other doses (10(-9) and 10(-6) M). After five pulses at 30-min intervals, the LH release rate in hamster cells was depressed 65%. Release was depressed 80% by pulses at 12-min intervals. Thus, in rats, desensitization is both frequency and dose dependent, whereas in hamsters, it is independent of frequency and dose. Stimulation with 10(-6) M GnRH pulses completely overcame desensitization in both species. Continuous exposure of anterior pituitary cells to 10(-8) M GnRH caused an initial rapid LH release, followed by a steady decline in the rate of release from peak rates to baseline levels by 2.5 h in both species. A 6-min, 10(-6) M GnRH pulse given immediately after a 3-h 10(-8) M GnRH exposure rapidly stimulated the cells to release LH at rates up to 192% of initial rates. When these pulses were continued at 30-min intervals, additional desensitization occurred. This overcoming of desensitization shows that desensitized anterior pituitary cells are not refractory to GnRH and suggests that the GnRH regulation of LH release may involve more than one GnRH receptor-mediated phenomenon.
Animals↗
Decreased 6-hydroxymelatonin excretion in Korsakoff's psychosis.
Mean (+/- SEM) urinary excretion rate of the major melatonin metabolite 6-hydroxymelatonin (micrograms/day) was lower in 7 (2.8 +/- 1.0) of 8 men with Korsakoff's psychosis (KP) than in 15 healthy men (11.4 +/- 1.4). Treatment with the alpha 2-noradrenergic agonist clonidine decreased daily 6-hydroxymelatonin excretion (p less than 0.02). Reduced daily excretion of 6-hydroxymelatonin in KP reflects decreased melatonin synthesis in the pineal gland, perhaps as a residual effect of lesions due to past thiamine deficiency (Wernicke's encephalopathy).
Aged↗
Light and propranolol suppress the nocturnal elevation of serotonin in the cerebrospinal fluid of rhesus monkeys.
Markedly elevated nighttime concentrations of serotonin in rhesus monkey cerebrospinal fluid were reduced to daytime levels by exposing the monkeys to continuous light or to the beta-adrenergic antagonist propranolol. Nighttime elevations of melatonin in cerebrospinal fluid were also suppressed by propranolol and light. Serotonin released in large quantities at night appears to be regulated like melatonin, and may act as a cerebroventricular hormone to influence brain and pituitary function at night.
Animals↗
Tetrahydropterin therapy for hyperphenylalaninemia caused by defective synthesis of tetrahydrobiopterin.
A patient with hyperphenylalaninemia caused by a defect in the synthesis of tetrahydrobiopterin was treated with 6-methyltetrahydropterin. This synthetic analog of the naturally occurring hydroxylation cofactor tetrahydrobiopterin, when given orally at a daily dose of 20 mg per kilogram of body weight increased depressed plasma and cerebrospinal fluid levels of norepinephrine. At a daily dose of 8 mg/kg, this pterin increased depressed cerebrospinal fluid levels of the biogenic amine metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. At these doses of 6-methyltetrahydropterin, there was an improvement of the patient's neurological symptoms, including a pronounced decrease in eye rolling and drooling and a marked increase in muscle strength, coordination, and physical activity.
Biopterins↗
Effect of clorgyline (a MAO type A inhibitor) on locomotor activity in the Syrian hamster.
Syrian hamsters in a lighting schedule of 14 h of light per day (LD 14:10) and housed in cages equipped with running wheels exhibited a clear onset of locomotor activity during the 1st h after lights off. Implantation of osmotic minipumps containing clorgyline (2 mg . kg-1 . day-1), an irreversible inhibitor of monoamine oxidase type A, caused a 1.5-h delay in the onset of wheel running by the 7th day of treatment. Increasing dosages of clorgyline (0.5, 1, 2, or 4 mg . kg-1 . day-1) caused increasing delays. Hamsters shifted from LD 14:10 to LD 10:14 underwent a 3-h advance in the onset of wheel running. Animals treated with clorgyline (2 mg . kg-1 . day-1) exhibited a markedly slowed rate of advance in activity onset, which did not prevent the short photoperiod from inhibiting reproductive function. Additionally, removal of the pineal gland did not affect wheel-running onset and did not prevent the delay in activity onset during clorgyline treatment. Hamsters in LD 14:10 were "released" into constant darkness (DD) for 3 days to prevent masking of activity onsets and offsets by light. Delays in activity onset in LD 14:10 caused by clorgyline (2 mg . kg-1 . day-1) persisted when these animals were released into DD. Activity offset in LD 14:10 occurred at lights on before and during clorgyline treatment but was delayed when the treated animals were maintained in DD. Drug-induced delays in both activity onset and offset suggest that clorgyline is not simply shortening the duration of activity or changing the expression of activity relative to the light-dark cycle, but is delaying the phase position of the circadian rhythm in locomotor activity. Clorgyline may act directly on the central oscillatory mechanism that drives the rhythm.
Animals↗
Melatonin-induced increase in cytoplasmic estrogen receptor activity in hamster uteri.
The pineal gland hormone, melatonin, has been shown to influence the growth and metabolism of uterine tissue in the Syrian hamster. Because the uterus is an estrogen-responsive target tissue, we studied the effect of melatonin on the unoccupied estrogen receptor (ER) activity of immature hamster uteri in vivo and in vitro. A single sc injection of 2.5 micrograms melatonin increased the ER activity of uterine cytosol (Rc) 30% within 60 min [from 147.4 +/- 14.1 (SE), to 191.8 +/- 18.5 fmol/mg protein]. Scatchard analysis showed the induced population of receptor to be homogeneous and of high affinity, with an equilibrium dissociation constant (Kd = 0.08 nM) similar to that for uteri for vehicle-treated animals. The induction of Rc by melatonin persisted for 90 min, but Rc returned to control levels by 2 h after injection. Scatchard analysis of unoccupied nuclear receptor showed no significant differences either in the quantity of receptor (vehicle = 379.7 +/- 46.7, melatonin = 396.9 +/- 76.7 fmol/mg protein) or in the Kd (vehicle = 0.75 nM, melatonin = 0.60 nM) between these two groups. In vitro incubation of fresh whole uteri for 60 min in media containing 10(-5) M melatonin increased Rc by 83% (from 41.3 +/- 10.7 to 75.4 +/- 11.0 fmol/mg protein), supporting a direct effect of melatonin on uterine tissue. The Rc induced by melatonin both in vivo and in vitro was sensitive to the degree of homogenization used in preparation of the cytosol. Whereas conservative homogenization (two 10-sec bursts with an intermittent 40-sec cooling period) of uteri from melatonin-treated animals was associated with a significant increase in Rc, homogenization for 60 sec without intermittent cooling showed a significant decrease (from 251.1 +/- 17.4 to 182.7 +/- 5.8 fmol/mg protein) as compared with uteri from vehicle-treated animals. Whole organ analysis of uteri from animals injected with melatonin followed by [3H]estradiol, in which no homogenization was used, demonstrated a 26% increase in Rc specific binding, confirming induction as the primary response to melatonin. These findings demonstrate the ability of melatonin to modulate ER activity in hamster uteri, and may help explain the effects of melatonin on uterine growth and metabolism.
Animals↗
Diurnal rhythms of serotonin in monkey cerebrospinal fluid.
Explore the source record for details and available documents.
Animals↗
Clorgyline delays the phase-position of circadian neurotransmitter receptor rhythms.
The number of alpha- and beta-adrenergic, muscarinic cholinergic, opiate, and benzodiazepine receptors in rat forebrain, and dopamine and benzodiazepine receptors in striatum, change throughout the day. The diurnal rhythms of these receptors were altered by treatment with the monoamine-oxidase inhibitor clorgyline: following treatment some or all rhythm characteristics of wave form, amplitude, 24-h mean, and phase, were affected. One common effect of treatment was a delay in phase-position of binding to alpha- and beta-adrenergic, opiate and benzodiazepine receptors. Additionally, the nocturnal elevation in pineal melatonin which normally returns to baseline at light onset, persisted 3 h into the light period after clorgyline administration. These biochemical observations extend behavioural findings that clorgyline can delay the phase-position of rodent nocturnal activity onset, and does so by slowing the central circadian pacemaker.
Animals↗
Decreased nocturnal plasma melatonin peak in patients with estrogen receptor positive breast cancer.
Plasma melatonin concentrations were determined over a period of 24 hours in 20 women with clinical stage I or II breast cancer. In ten of the patients, whose tumors were estrogen receptor positive, the nocturnal increase in plasma melatonin was much lower than that observed in eight control subjects. Women with the lowest peak concentration of melatonin had tumors with the highest concentrations of estrogen receptors. A significant correlation was found between the peak plasma melatonin concentration and the tumor estrogen receptor concentration in 19 of the patients. These data suggest that low nocturnal melatonin concentrations may indicate the presence of estrogen receptor positive breast cancer and could conceivably have etiologic significance.
Adult↗
Pineal melatonin in the Djungarian hamster: photoperiodic regulation of a circadian rhythm.
The pineal melatonin rhythm has been proposed to represent a physiological signal which mediates the effects of photoperiod in a variety of seasonal breeding mammals. Studies in other species have led to the hypothesis that an endogenous circadian mechanism controls pineal melatonin content and can adapt the melatonin rhythm to reflect shifts in the prevailing light-dark schedule. In this report, photoperiodic regulation of the pineal melatonin content was investigated in the male Djungarian hamster, a species that is a long day breeder and photo-periodic from early life. In the first study, a daily pineal melatonin rhythm persisted after 6-8 weeks of constant dark conditions in a specific phase relationship to the onset of wheel running activity. Pineal melatonin levels increased around the time of activity onset, and high values persisted for 14-17 h. In subsequent studies, adult males [previously maintained under long days (16 h of light and 8 h of darkness)] were subjected to one of three conditions: 1) a 3-h advance in the onset of darkness, 2) a delay in the time of light onset, or 3) both alterations in the photoperiod. The acute 3-h advance in onset of the dark period caused an earlier rise in pineal melatonin production by approximately 1.5 h compared to that in controls. In contrast, the falling phase of the pineal melatonin rhythm was not altered by extension of the dark period. Therefore, aspects of the pineal melatonin pattern, i.e. the rising phase and peak duration, reflected changes in the photoperiod, while the falling phase anticipated the onset of the light period predicted by the previous light-dark schedule. These observations support the hypothesis that melatonin production by the pineal is an endogenous circadian rhythm and, as a physiological signal, may convey information about the daylength.
Animals↗
Pineal is required for testicular maintenance in the turkish hamster (mesocricetus brandti).
The effect of pinealectomy on reproductive function was examined in the Turkish hamster, Mesocricetus brandti. Pinealectomy resulted in testicular regression in this species. This result was unexpected since pinealectomy prevents short day-induced regression of the gonads in the closely related Syrian hamster, Mesocricetus auratus. Decentralization of the superior cervical ganglia and exposure to continuous illumination also caused testicular regression in the Turkish hamster. These manipulations are believed to block pineal melatonin synthesis. In each case (i.e. pinealectomy, decentralization of the superior cervical ganglia, exposure to continuous illumination), the testes regressed after approximately 3--9 weeks and underwent recrudescence after approximately 16--28 weeks. This cycle of testicular regression and recrudescence was similar to that observed in Turkish hamsters exposed to a short day photoperiod. In further experiments, the effects of exogenous melatonin were studied in Turkish and Syrian hamsters. The results of these studies suggest that, in Turkish hamsters, pineal melatonin may be involved in both the maintenance of testis function during exposure to a long day photoperiod and also in the suppression of reproductive function in short days. This is in contrast to the Syrian hamster, in which melatonin appears to be important only for inhibition of gonadal function in short days.
Animals↗
Daily rhythm of plasma melatonin in normal and precocious puberty.
A previous study of normal humans has shown a decrease in plasma melatonin at the onset of puberty, suggesting that melatonin may act to restrain pubertal onset. We have measured plasma melatonin throughout a 24-h period in normal and constitutionally short males at different pubertal stages and in patients with idiopathic true precocious puberty and familial male isosexual precocity. The 24-h profile of plasma melatonin was similar for the prepubertal, pubertal, and adult males studied, with all subjects having low levels (20-50 pg/ml) during the day and high levels (80-100 pg/ml) at night between 0100-0500 h. The 24-h profiles of the patients with isosexual precocity were similar to the profiles observed throughout normal puberty. These data do not support a role for melatonin in the initiation of normal or precocious puberty in man.
Adolescent↗
The daily profile of plasma melatonin in obese and Prader-Willi syndrome children.
Daily plasma melatonin profiles were determined by RIA in exogenously obese and Prader-Willi syndrome children. The melatonin RIA was validated for use in human plasma by evaluating melatonin immunoreactivity in the resultant eluate fractions of a high performance liquid chromatogram of a chloroform-extracted pooled human plasma sample. Melatonin immunoreactivity in the plasma profile occurred only in the fraction that corresponded to the chromatographic position of authentic melatonin. Exogenously obese patients had plasma melatonin profiles characterized by low levels during the day (20-30 pg/ml plasma) and high levels at night (65-130 pg/ml plasma). The plasma melatonin profile did not vary as a function of weight or pubertal status. Prader-Willi syndrome patients had similar melatonin profiles to those of exogenously obese patients. Although the Prader-Willi children had a delayed onset of puberty, the plasma melatonin profile was unaltered. These data indicate that plasma melatonin may not play a role in the onset of puberty. However, the daily melatonin profile is a temporally precise hormonal rhythm in humans.
Child↗