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M. D. Rollag

Bio: M. D. Rollag is an academic researcher from Colorado State University. The author has contributed to research in topics: Melatonin & Radioimmunoassay. The author has an hindex of 2, co-authored 2 publications receiving 751 citations.

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Journal ArticleDOI
TL;DR: A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light and returned to peak levels when the lights were turned off 3.5 h later.
Abstract: A specific and sensitive double-antibody radioimmunoassay for melatonin (N-acetyl-5-methoxytryptamine) has been developed utilizing rabbit antisera to a bovine serum albumin conjugate of N-succinyl-5-methoxytryptamine and utilizing N-3-(4-hydroxyphenl)-propionyl-5-methoxytryptamine for radioiodination. The least detectable concentration of melatonin standard was 10 pmolar (2.3 pg/tube) with 50% inhibition resultinhibition curves obtained with increasing quantities of melatonin or increasing quantities of chloroform extracts of ovine sera were parallel. The immunoreactivity found in ovine sera c-migrated with [3H]melatonin on silica gel G when developed with chloroform:methanol (9:1). N-Acetylserotonin, 5-methoxytryptamine, serotonin, tryptophan, 6-hydroxymelatonin, 6-methoxytetrahydroharmalan, and several other indole and beta-carboline compounds do not influence the estimation of melatonin in the radioimmunoassay. Concentrations of melatonin could be accurately determined when 31 to 1000 pg were added to 1 ml ovine serum. Serum samples with melatonin concentrations of 1000 pg/ml, 500 pg/ml and 75 pg/ml had intra-assay coefficients of variation of 9.1%, 8.6%, and 17.4%, respectively. The respective inter-assay coefficients of variation were 22.7%, 18.1%, and 37.1%. Ewes exposed to a 12 h light: 12 h dark lighting regimen demonstrated a circadian rhythm in serum concentrations of melatonin. Concentrations ranged from 10-30 pg/ml during periods of light to 100-300 pg/ml during periods of dark. During exposure to continuous light, the circadian rhythm was abolished and concentrations of melatonin were maintained at 10-50 pg/ml. When exposed to conditions of continuous dark the circadian rhythm persisted. A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light. Concentrations returned to peak levels when the lights were turned off 3.5 h later.

661 citations

Journal ArticleDOI
TL;DR: In this paper, the proportion of the total melatonin output which is secreted directly into the third ventricle of sheep, samples of blood from the jugular vein and of cerebrospinal fluid (CSF) from the cisterna magna were obtained during 128min intervals on three consecutive nights from four ewes.
Abstract: To determine the proportion of the total melatonin output which is secreted directly into the third ventricle of sheep, samples of blood from the jugular vein and of cerebrospinal fluid (CSF) from the cisterna magna were obtained during 128-min intervals on three consecutive nights from four ewes. Blood was withdrawn continuously at a rate of 3 ml/min and pooled into 1-min fractions. Simultaneously with the collection of blood, 0.5-ml samples of CSF were obtained from the cisterna magna every 4 min. Melatonin concentrations were quantified in all samples by radioimmunoassay. During the sampling interval of the first night, lights were left on for 32 min, turned off for 64 min, and then turned back on for an additional 32 min. These samples were utilized to obtain the concentration profiles of melatonin in jugular blood and cisternal CSF during an endogenous surge of melatonin secretion. Plasma concentrations of melatonin remained between 10 and 100 pg/ml in two Corriedale crossbred ewes and between 200 an...

96 citations


Cited by
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Journal ArticleDOI
TL;DR: The pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine, and since the mid 1960s, research on the gland has become a very active area of investigation.
Abstract: I Introduction UNTIL 35 yr ago, most scientists did not take research on the pineal gland seriously The decade beginning in 1956, however, provided several discoveries that laid the foundation for what has become a very active area of investigation These important early observations included the findings that, 1), the physiological activity of the pineal is influenced by the photoperiodic environment (1–5); 2), the gland contains a substance, N-acetyl-5-methoxytryptamine or melatonin, which has obvious endocrine capabilities (6, 7); 3), the function of the reproductive system in photoperiodically dependent rodents is inextricably linked to the physiology of the pineal gland (5, 8, 9); 4), the sympathetic innervation to the pineal is required for the gland to maintain its biosynthetic and endocrine activities (10, 11); and 5), the pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine (12) Since the mid 1960s, research on t

2,134 citations

Journal ArticleDOI
12 Dec 1980-Science
TL;DR: Findings establish that the human response to light is qualitatively similar to that of other mammals.
Abstract: Bright artificial light suppressed nocturnal secretion of melatonin in six normal human subjects. Room light of less intensity, which is sufficient to suppress melatonin secretion in other mammals, failed to do so in humans. In contrast to the results of previous experiments in which ordinary room light was used, these findings establish that the human response to light is qualitatively similar to that of other mammals.

1,776 citations

Journal ArticleDOI
TL;DR: The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cellphotopigments for vision.
Abstract: The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

1,708 citations

Journal ArticleDOI
19 Apr 1996-Science
TL;DR: Cultured neural retinas of the golden hamster exhibited circadian rhythms of melatonin synthesis for at least 5 days at 27°C, and retinas from hamsters homozygous for the circadian mutation tau showed a shortened free-running period ofmelatonin synthesis.
Abstract: Many retinal functions are circadian, but in most instances the location of the clock that drives the rhythm is not known. Cultured neural retinas of the golden hamster (Mesocricetus auratus) exhibited circadian rhythms of melatonin synthesis for at least 5 days at 27 degrees celsius. The rhythms were entrained by light cycles applied in vitro and were free-running in constant darkness. Retinas from hamsters homozygous for the circadian mutation tau, which shortens the free-running period of the circadian activity rhythm by 4 hours, showed a shortened free-running period of melatonin synthesis. The mammalian retina contains a genetically programmed circadian oscillator that regulates its synthesis of melatonin.

703 citations

Journal ArticleDOI
TL;DR: The aim of this review is to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis, which reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism.
Abstract: Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

672 citations