Melatonin: Identification of Sites of Antigonadal Action in Mouse Brain

Glass, John D.; Lynch, G. Robert

doi:10.1126/science.7292016

Cited by 112 publications

(43 citation statements)

References 33 publications

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“…Studies using intracerebral melatonin implants have however indicated that the photoperiodic effects of melatonin are mediated via a site in or near the hypothalamus (10)(11)(12). The results of the present study show discretely localized high-affinity melatonin receptors restricted to the hypothalamus and epithalamus of the brain and the purs tuberalis of the pituitary.…”

Section: Discussionsupporting

confidence: 55%

“…The localization of these low-affinity receptors within the brain, pituitary and other tissues is remarkably ubiquitous and, as yet, their physiological significance is unknown (4)(5)(6)(7)(8)(9). The widespread distribution found for the low-affinity melatonin receptor contrasts with reports that the photoperiodic effects of melatonin can only be induced by very localized intracerebral administration of the compound (10)(11)(12).…”

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confidence: 39%

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Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

Williams¹,

Morgan²,

Hastings³

et al. 1989

J Neuroendocrinology

121

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A high-affinity, discretely localized melatonin receptor has been characterized and mapped within the brain and pituitary of the Syrian hamster using the high specific activity ligand [ '251] In mammals, the pineal hormone melatonin is synthesized and secreted into the circulation with a precise nocturnal rhythm (I). The melatonin signal thus acts as an endocrine representation of the dark-phase (2). Melatonin has been shown to influence a variety of processes, including circadian cycles of activity in the rat (3) and seasonal reproductive cyclicity in photoperiodic species such as the sheep and the hamster (1). The mode of action of melatonin is, however, obscure due to the fact that the sites of action of the hormone have remained unidentified. A number of studies have documented relatively lowaffinity melatonin receptors (K, within the nanomolar range) using membrane homogenate receptor assays. The localization of these low-affinity receptors within the brain, pituitary and other tissues is remarkably ubiquitous and, as yet, their physiological significance is unknown (4-9). The widespread distribution found for the low-affinity melatonin receptor contrasts with reports that the photoperiodic effects of melatonin can only be induced by very localized intracerebral administration of the compound (10-12).The use of in vitro receptor-site autoradiography in conjunction with membrane homogenate receptor assays, utilizing the high specific activity ligand [1251]iodomelatonin, has led to the identification of discretely localized melatonin receptors in the brain and pituitary of the foetal and adult hamster (13,14), the adult rat (15-19) and the ovine pituitary (20). Using the same combined approach, we have investigated the distribution and characteristics of a high-affinity melatonin receptor in the brain and pituitary of the adult Syrian hamster, an animal used extensively to study the influence of melatonin on circadian rhythmicity and seasonal reproduction.

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Section: Discussionsupporting

confidence: 55%

contrasting

confidence: 39%

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

Williams¹,

Morgan²,

Hastings³

et al. 1989

J Neuroendocrinology

121

View full text Add to dashboard Cite

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“…Simple SD exposure (Pyter et al 2005a) or administration of melatonin in LD via timed injections (Hall et al 1985) or subcutaneous (Johnston et al 1980a) or central (i.e., anterior hypothalamus) implants (Glass et al 1987) induce gonad regression in white-footed mice (Johnston et al 1980a;Johnston et al 1980b). As with other seasonal breeders, melatonin-induced gonad regression occurs when GnRH release from the hypothalamus is down-regulated (Glass et al 1981;Glass et al 1987), eliminating tonic LH stimulation of the gonads (Glass et al 1988) and ultimately apoptosis of the testes (Young et al 2000). It is surprising that others species do not respond to 6-MBOA as white-footed mice given the similarity in chemical structure between 6-MBOA and melatonin.…”

Section: Discussionmentioning

confidence: 99%

6-MBOA affects testis size, but not delayed-type hypersensitivity, in white-footed mice (Peromyscus leucopus)

Martin

Johnson

Hutch

et al. 2008

Comparative Biochemistry and Physiology Part A: Molecular &

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Many rodents use day length to time reproduction to occur when resources are abundant, but some species also use supplementary environmental cues. One supplementary cue is the plant-derived compound, 6-methoxy-2-benzoxazolinone (6-MBOA). Most rodents grow their gonads in response to 6-MBOA in their diets, but it is presently unknown whether they also use 6-MBOA to adjust other aspects of physiology, specifically their immune systems. 6-MBOA is structurally similar to melatonin, and seasonal changes in rodent immune activities are often mediated by melatonin. We therefore predicted that white-footed mice (Peromyscus leucopus), which breed seasonally and are reproductively sensitive to melatonin, would adjust their immune systems when fed 6-MBOA. 6-MBOA treated mice in long day lengths regressed their testes to a greater extent than mice fed a standard diet, or mice kept in short day lengths and fed 6-MBOA or a standard diet. One type of immune activity (delayed-type hypersensitivity) was not affected by 6-MBOA, however, although responses were greater in short versus long day mice. In sum, P. leucopus responded reproductively to 6-MBOA, although differently than other species; immune activity was unaffected. Other aspects of the immune system, especially in herbivorous rodents, may be affected by 6-MBOA and thus warrant further study.

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“…Glass and Lynch (14) and Glass and Knotts (13) demonstrated that melatonin-containing pellets implanted in the medial preoptic area, AH, and supra-and retrochiasmatic areas elicit gonadal regression during LD to the same extent as SD exposure. Because melatonin from the pellets was found to diffuse to a distance of only 0.2 mm, and similar doses of melatonin delivered subcutaneously could not trigger testicular regression, it is likely that these neural sites mediate the antigonadal action of melatonin (13,14).…”

Section: Discussionmentioning

confidence: 99%

Response to selection for photoperiod responsiveness on the density and location of mature GnRH-releasing neurons

Avigdor¹,

Sullivan²,

Heideman³

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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-Natural variation in neuroendocrine traits is poorly understood, despite the importance of variation in brain function and evolution. Most rodents in the temperate zones inhibit reproduction and other nonessential functions in short winter photoperiods, but some have little or no reproductive response. We tested whether genetic variability in reproductive seasonality is related to individual differences in the neuronal function of the gonadotropin-releasing hormone network, as assessed by the number and location of mature gonadotropin-releasing hormonesecreting neurons under inhibitory and excitatory photoperiods. The experiments used lines of Peromyscus leucopus previously developed by selection from a wild population. One line contained individuals reproductively inhibited by short photoperiod, and the other line contained individuals nonresponsive to short photoperiod. Expression of mature gonadotropin-releasing hormone (GnRH) immunoreactivity in the brain was detected using SMI-41 antibody in the single-labeled avidin-biotin-peroxidase-complex method. Nonresponsive mice had 50% more immunoreactive GnRH neurons than reproductively inhibited mice in both short-and long-day photoperiods. The greatest differences were in the anterior hypothalamus and preoptic areas. In contrast, we detected no significant within-lines differences in the number or location of immunoreactive GnRH neurons between photoperiod treatments. Our data indicate that high levels of genetic variation in a single wild population for a specific neuronal trait are related to phenotypic variation in a life history trait, i.e., winter reproduction. Variation in GnRH neuronal activity may underlie some of the natural reproductive and life history variation observed in wild populations of P. leucopus. Similar genetic variation in neuronal traits may be present in humans and other species. genetic variation; artificial selection; seasonality; evolutionary physiology; brain variation; gonadotropin-releasing hormone WITHIN-POPULATION GENETIC VARIATION regulating the abundance, location, and connections of neurons must contribute to evolution of brain function. Similarly, natural genetic variation in neuronal traits is presumably responsible for some proportion of intraspecific functional variation in vertebrates. Because neural circuitry regulates reproductive physiology and behavior, neural variation is likely to explain some unknown proportion of life history variation within as well as among species. At present, almost nothing is known about natural levels of genetically based neuroendocrine physiological variation related to life history variation within species of mammals. The physiological link between genes and life history patterns is important because genes must act on life history traits through physiological mechanisms, and thus physiological variation may shape or constrain life history evolution (16). Understanding natural neuroendocrine variation related to life history traits might help us learn how rapidly brains adapt to current cha...

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Melatonin: Identification of Sites of Antigonadal Action in Mouse Brain

Cited by 112 publications

References 33 publications

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

6-MBOA affects testis size, but not delayed-type hypersensitivity, in white-footed mice (Peromyscus leucopus)

Response to selection for photoperiod responsiveness on the density and location of mature GnRH-releasing neurons

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Melatonin: Identification of Sites of Antigonadal Action in Mouse Brain

Cited by 112 publications

References 33 publications

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [125|]lodomelatonin*

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [125|]lodomelatonin*

6-MBOA affects testis size, but not delayed-type hypersensitivity, in white-footed mice (Peromyscus leucopus)

Response to selection for photoperiod responsiveness on the density and location of mature GnRH-releasing neurons

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Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*

Melatonin Receptor Sites in the Syrian Hamster Brain and Pituitary. Localization and Characterization Using [¹²⁵|]lodomelatonin*