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H J Lynch

Publications and source records attributed to H J Lynch.

At least 19 recordsLinked to original sources
PubMed1991

Melatonin and its precursors in Y79 human retinoblastoma cells: effect of sodium butyrate.

We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for 3 days. This protocol dramatically increased the release of melatonin and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine (10 microM) or L-DOPA (100 microM) markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation (e.g. treatment with sodium butyrate) can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 cells. The inhibition of melatonin release by dopamine supports the hypothesis that in these cells, melatonin and dopamine are components of a retinal feedback loop.

5-Hydroxytryptophan↗
PubMed1990

Melatonin concentrations in the sudden infant death syndrome.

To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean +/- S.E.M., 2.6 +/- 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 +/- 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 +/- 29 pmol/l; n = 32) than among those dying of other causes (180 +/- 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 +/- 23, n = 30 vs. 144 +/- 22 pmol/l, n = 33) and vitreous humor (68 +/- 21, n = 10 vs. 81 +/- 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Age Factors↗
PubMed1988

The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women.

Plasma melatonin, PRL, and LH levels were measured in samples collected every 2 h for 24 h from 14 normally cycling women during the early follicular, periovulatory, and luteal phases of their menstrual cycles. Plasma melatonin levels also were measured in samples collected at the same interval from 7 patients with hypothalamic amenorrhea. A distinct daily rhythm in plasma melatonin was evident in all subjects, with peaks occurring around 0300 h. Each woman's rhythm was remarkably consistent throughout the menstrual cycle (in terms of the phase, amplitude, and total melatonin secreted). Plasma PRL levels also exhibited daily rhythms which did not change during the menstrual cycle; the nocturnal peak plasma PRL level tended to occur 1-2 h after that for melatonin. Among the amenorrheic women, both daytime and nighttime melatonin levels were significantly higher (P less than 0.005) than in the normal women. Their plasma PRL levels were similar to those in the normal women. We conclude that, as for PRL, the circadian rhythm of melatonin secretion does not change significantly during the normal menstrual cycle. The elevated plasma melatonin levels in women with hypothalamic amenorrhea suggest that the hormone may be involved in the neuroendocrine pathology underlying this disorder.

Adult↗
PubMed1987

A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol.

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.

Adult↗
PubMed1987

Melatonin in human preovulatory follicular fluid.

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCH to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations [36.5 +/- 4.8 (+/- SEM) pg/mL] substantially higher than those in the corresponding serum (10.0 +/- 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Chromatography, Thin Layer↗
PubMed1986

Plasma and pineal melatonin levels in female ferrets housed under long or short photoperiods.

Ovohysterectomized female ferrets were housed in controlled environment rooms in which the daily lighting schedule was either 15L:9D (long days) or 9L:15D (short days). After 2 weeks some ferrets in each group were given an intrajugular catheter: beginning 1 week later, a blood sample was taken daily at one of eight different clock times over an 8 to 10 day period. One additional blood sample plus the pineal gland were collected from these animals and from uncathetarized animals in each group after decapitation at different clock times. Both plasma melatonin concentrations and pineal melatonin content were elevated in a square-wave pattern during the dark hours, with the duration of elevation being longer in ferrets kept under the short days. These results suggest that differences in the duration of nocturnal increments in melatonin secretion may mediate the stimulatory and inhibitory effects of long and short days, respectively, on ovarian activity in female ferrets.

Animals↗
PubMed1986

Pineal responses to stress.

When laboratory rats are sensitized by appropriate environmental manipulations (e.g., protracted exposure to light, fasting), significant increases in melatonin synthesis and secretion can be induced by the acute imposition of stress (e.g., physical immobilization). In the absence of such priming pre-treatment, however, a stress-induced increment in melatonin levels may not be detectable. The mechanisms responsible may involve concurrent changes in the sensitivity of the pineal to catecholamines, sympathetic neural input to the gland, and circulating levels of catecholamines. The experimental use of stress-induced changes in pineal function may enhance the utility of the laboratory rat's pineal gland as a model for studying changes in the rhythmic secretion of melatonin in humans as a consequence of endogenous processes.

Animals↗
PubMed1985

Possible behavioral consequences of light-induced changes in melatonin availability.

Melatonin is a hormone secreted at night, in the dark, by the human pineal organ. This nocturnal release of melatonin, in humans and other species, is rapidly suppressed by exposure to sufficiently bright light. In humans, the function, if any, of this circadian pattern of melatonin release has not been determined. In fact, no function has been definitively attributed to the hormone melatonin in humans. In one study, conducted in our laboratory, pharmacologic doses of oral melatonin (240 mg over two hours) were administered to volunteers, and various behavioral parameters were assessed. Melatonin had substantial, but brief, sedative-like effects on mood and performance. Thus it appears that a mechanism exists, whereby light, of sufficient intensity to affect melatonin release in humans, can affect behavior. It can be hypothesized that sufficiently bright light, acting by way of the suppression of melatonin release, can acutely increase alertness or act as a zeitgeber (synchronizer of circadian cycles). The light intensity necessary to suppress melatonin secretion in humans is well above typical indoor lighting conditions, but well below normal outdoor daytime levels of illumination. Therefore, the hypothesis that light may affect behavior or circadian patterns of sleep and waking, if found to be true, could have considerable impact on the design of interior lighting.

Double-Blind Method↗
PubMed1984

Effects of melatonin on human mood and performance.

The function of melatonin, a hormone secreted by the pineal gland primarily at night, has not been definitively established in humans. To determine if pharmacologic doses of melatonin had any behavioral effects it was administered acutely to 14 healthy men. Their mood, performance, memory and visual sensitivity were assessed. Plasma melatonin concentration was assayed as well. Melatonin significantly decreased self-reported alertness and increased sleepiness as measured by the Profile of Mood States and the Stanford Sleepiness Scale self-report mood questionnaires. The effects were brief. Melatonin also affected performance, slowing choice-reaction time but concurrently decreasing errors of commission. Sustained fine motor performance was not impaired after melatonin administration nor were the tests of memory and visual sensitivity that were administered. It is concluded that melatonin, administered orally in pharmacological quantities, has significant but short acting sedative-like properties.

Adolescent↗
PubMed1984

Light intensities required to suppress nocturnal melatonin secretion in albino and pigmented rats.

Sprague-Dawley albino rats or Long-Evans pigmented rats were exposed during the dark phase of the daily light:dark cycle to various intensities of a sunlight-stimulating white fluorescent light (0.022, 0.044, 0.110, 0.220, 0.440 or 2.200 microW/cm2) for 30 min; pineal glands and trunk blood samples were then collected and assayed for melatonin by radioimmunoassay. Albino rats exposed to irradiances of 0.110 microW/cm2 or less had pineal melatonin levels that were not significantly different from those of unexposed animals; higher irradiances significantly (P less than 0.001) reduced melatonin levels. In contrast, as little as 0.022 microW/cm2 significantly (P less than 0.02) reduced pineal and serum melatonin levels in the pigmented rats. These results suggest that something other than the simple presence or absence of eye pigmentation is the critical factor in determining the sensitivity of the rat's pineal to retinal-mediated photic suppression of melatonin synthesis.

Albinism↗
PubMed1984

Bioavailability of oral melatonin in humans.

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Administration, Oral↗
PubMed1981

Light intensity and the control of melatonin secretion in rats.

The effect of varying ambient light intensity on the phase and amplitude of urinary melatonin rhythms was studied in rats housed individually in metabolism cages. For 17 days one group (D) was exposed to alternating 12-hour periods of dim light (0.1-0.3 micro/cm2) and total darkness; a second group (L) was exposed alternately to dim light and bright ligh (45-110 micro/cm2). All animals were then exposed to constant dim light for 15 days, after which they were returned to their original lighting regimens (D or L). 18 days later, half of each group was killed at the midpoint of the dim light phase, and the other half 12 h later. Both groups excreted melatonin rhythmically when exposed to daily cycles in light intensity; the L animals excreted 69% of the total daily melatonin output during the dim light phase and the D group of rats excreted 70% during the dark phase. When placed under continuous dim light, L animals continued to excrete melatonin as before, but D rats excreted significantly less, and the melatonin rhythm was dampened. When returned to a diurnal light cycle, both groups again exhibited rhythms in melatonin excretion that were entrained to the light cycle. Animals killed at the time of day coinciding with diminished melatonin excretion had lower pineal and serum melatonin levels (0.2 +/- 0.1 ng/pineal; 30 +/- 8 pg/ml serum) than those killed 12 h later (2.0 +/- 0.4 ng/pineal; 57 +/- 20 pg/ml serum). These observations provide additional evidence that measurement of urinary melatonin levels gives an accurate index of melatonin secretion from the rat pineal. They also show that a given light intensity presented for a part of the 24-hour day (e.g., dim light; 0.1-0.3 micro/cm2) can be interpreted by the mammalian pineal as light or dark, depending on the light intensity available during the rest of the day.

Animals↗
PubMed1979

Effect of cyclic changes in environmental lighting and ambient temperature on the daily rhythm in melatonin excretion by rats.

Melatonin excretion was measured by radioimmunoassay in 6 h or 12 h urine specimens from individual control rats and from animals previously blinded by bilateral orbital enucleation. Among sighted rats, the rate of melatonin excretion was greatest during the daily 12 h of darkness (1.44 +/- 0.06 ng/12 h dark period vs. 0.53 +/- 0.07 ng/12 h light period; P less than 0.001). Moreover, greater quantities of melatonin were excreted in the latter half of the dark period than in the first half (e.g. 0.55 +/- 0.08 ng/first 6 h vs 0.97 +/- 0.05 ng/second 6 h; P less than 0.001). When the onset of the daily light period was shifted forward by 12 h, 5--7 days were needed for the daily rhythm in melatonin excretion to become re-entrained to the new light--dark cycle. Among blinded rats, the rate of melatonin excretion also varied rhythmically; however, the rhythm was neither synchronized with the light-dark cycle nor influenced by alterations in the lighting schedule. Similarly, artificial cycles in environmental temperature were not effective in entraining the daily rhythm in melatonin excretion among blinded rats.

Animals↗