Abstract:Using gas chromatography-negative ionization mass spectrometry, plasma melatonin levels in pinealectomized and sham-operated rats were assessed. The pinealectomized rats consistently demonstrated an absence of plasma melatonin while the intact animals showed detectable amounts. This suggests that although melatonin may be formed in tissues other than a pineal gland, the contribution to plasma is of pineal origin. Thus, plasma melatonin levels can be used as a marker of circadian melatonin secretion by the pine… Show more
“…In this simple preparation, responses to pharmacological agents applied directly to the SCN can be assessed unambiguously against the normally invariant basal rhythm. Application of 1 nM of melatonin, which is near physiological concentrations [19], directly to the SCN in this brain-slice preparation can reset the neuronal circadian rhythms [23]. When the medium in the brainslice chamber is replaced between CT 10 and CT i 1 by a warmed, oxygenated melatonin solution, the time-ofpeak, and thus the phase of the rhythm, on the next day in vitro is advanced by 4 h (Fig.…”
Section: Circadian Changes In the Sensitivity Of Scn Rhythms To Phasementioning
The biological clock in the suprachiasmatic nucleus (SCN) of the hypothalamus plays a well-defined role in regulating melatonin production by the pineal. Emerging evidence indicates that melatonin itself can feed back upon the SCN and thereby influence circadian functions. Melatonin administration has been shown to entrain activity rhythms in rodents and humans. Melatonin binds specifically within the SCN and alters SCN physiology by both acute and clock-resetting mechanisms. The circadian clock in the SCN appears to temporally restrict its own sensitivity to melatonin, such that physiological sensitivity is greatest in the subjective dusk period
“…In this simple preparation, responses to pharmacological agents applied directly to the SCN can be assessed unambiguously against the normally invariant basal rhythm. Application of 1 nM of melatonin, which is near physiological concentrations [19], directly to the SCN in this brain-slice preparation can reset the neuronal circadian rhythms [23]. When the medium in the brainslice chamber is replaced between CT 10 and CT i 1 by a warmed, oxygenated melatonin solution, the time-ofpeak, and thus the phase of the rhythm, on the next day in vitro is advanced by 4 h (Fig.…”
Section: Circadian Changes In the Sensitivity Of Scn Rhythms To Phasementioning
The biological clock in the suprachiasmatic nucleus (SCN) of the hypothalamus plays a well-defined role in regulating melatonin production by the pineal. Emerging evidence indicates that melatonin itself can feed back upon the SCN and thereby influence circadian functions. Melatonin administration has been shown to entrain activity rhythms in rodents and humans. Melatonin binds specifically within the SCN and alters SCN physiology by both acute and clock-resetting mechanisms. The circadian clock in the SCN appears to temporally restrict its own sensitivity to melatonin, such that physiological sensitivity is greatest in the subjective dusk period
“…Previous investigations of pinealectomized animals revealed substantial levels of an immunoreactive substance that was interpreted to be melatonin [reviewed by Lewy et al,13]. We further suggested that assay specificity in rats could be partially verified by demonstrating abolition of melatonin levels following pinealectomy and that circulating levels of melatonin could therefore be used to assess human pineal melatonin production, adrenergic tone in the pineal, light sensitivity and the phase of the endogenous circadian pacemaker (ECP) [15].…”
Section: Lewymentioning
confidence: 99%
“…Our assay was also instrumental in enabling us to demonstrate that virtually all measurable melatonin in the circulation of rats and humans is derived from the pineal gland [13,14]. Previous investigations of pinealectomized animals revealed substantial levels of an immunoreactive substance that was interpreted to be melatonin [reviewed by Lewy et al,13].…”
The most useful marker for human circadian phase position is the dim light melatonin onset (DLMO). This is optimally obtained by sampling blood or saliva in the evening at intervals of 30 min or less. Ambient light intensity should not exceed 30–50 lx. For many years, the DLMO was determined mainly with the ‘gold standard’ GCMS technique for measuring melatonin in human plasma. However, new and improved RIAs now provide the requisite sensitivity and accuracy (specificity) for detecting the time that low daytime levels begin to increase in the evening: the lower the operational threshold for the DLMO, the more reliable it is as a phase marker.
“…Animals were housed in groups of three to five, in clear plastic cages with food and water ad libitum. Rats were always sacrificed during the light phase of the light/dark cycle, between ZT6 and ZT8) (ZT, Zeitgeber time; ZT0 lights on), when the blood melatonin levels are the lowest (Lewy et al, 1980). All studies were carried out in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institutes of Health.…”
Section: Animalsmentioning
confidence: 99%
“…The effect of these ligands cannot be attributed to the presence of melatonin on the receptor, as at the time the animals were sacrificed, serum melatonin is very low (Lewy et al, 1980) and the effect was observed only during proestrus. The presence of MT 1 constitutively active receptors was previously demonstrated in rat arteries .…”
This study investigated the receptor mechanism(s) by which the hormone melatonin directly affects ovarian function. Expression of MT 1 and MT 2 melatonin receptor mRNA was detected in the rat ovaries both by reverse transcriptase-polymerase chain reaction and in situ hybridization with digoxigenin-labeled oligoprobes. Exposure of granulosa cells in culture to 17-estradiol seems to alter the state of melatonin receptor coupling. Indeed, the efficacy of 4P-PDOT on forskolin-stimulated cAMP formation was reversed from an MT 2 partial agonist in vehicle-treated cells to that of an MT 1 inverse agonist in 17-estradiol (0.1 M)-treated granulosa cells. We conclude that MT 1 and MT 2 melatonin receptors expressed in antral follicles and corpus luteum may affect steroidogenesis through cAMPmediated signaling. These results underscore the implications of the levels of ovarian estrogen when melatonin receptor ligands are used as therapeutic agents.
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