Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses
Abstract
The pineal hormone melatonin regulates seasonal reproductive function and modulates circadian rhythms in mammals. We now report the cloning and characterization of a high affinity receptor for melatonin from the sheep and human. The receptor cDNAs encode proteins that are members of a newly discovered group within the G protein-coupled receptor family. Expression of the sheep and human receptors in COS-7 cells results in high affinity 2-[125I]iodomelatonin binding and pharmacological characteristics similar to endogenous high affinity receptors. Functional studies of NIH 3T3 cells stably expressing the sheep receptor show that the mammalian melatonin receptor is coupled to inhibition of adenylyl cyclase through a pertussis toxin-sensitive mechanism. In situ hybridization studies of melatonin receptor mRNA in several mammals reveal hybridization signals in the hypophyseal pars tuberalis and hypothalamic suprachiasmatic nucleus. The cloned high affinity receptor likely mediates the reproductive and circadian actions of melatonin in mammals.
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The sequence of the MT1 PCR product from human adrenal was identical to bases 477-912 of human MT1 melatonin receptor mRNA.
“La secuencia de este producto fue idéntica a la secuencia entre las bases 477-912 del mARN del receptor MT1 de melatonina correspondiente a los dominios transmembrana 3-6 de la proteína”
From La melatonina reduce la respuesta de cortisol al ACTH en humanos (2008) · cites this paper as [29]
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- Authors
- Reppert, S. M., Weaver, D. R., & Ebisawa, T.
- Affiliations
- Harvard University (US)
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1994-11
- Volume
- 13
- Issue
- 5
- Pages
- 1177-1185
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2034348289
- Cited by
- 1,096
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 24 · 2023: 16 · 2022: 30 · 2021: 31 · 2020: 18 · 2019: 24 · 2018: 37 · 2017: 27 · 2016: 32 · 2015: 31 · 2014: 39 · 2013: 39 · 2012: 29
- FWCI
- 31.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk042125-08)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 42125)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- melatonin receptors, G protein-coupled receptors, sheep, human, adenylate cyclase inhibition, pertussis toxin-sensitive G proteins, circadian rhythm, reproductive function, pineal gland, suprachiasmatic nucleus, pars tuberalis, receptor cloning
- MeSH terms
- Cyclic AMP, Animals, Cloning, Molecular, Female, Cricetinae, Humans, Male, Melatonin, Molecular Sequence Data, Pituitary Gland, Receptors, Cell Surface, RNA, Messenger, Sheep, Suprachiasmatic Nucleus, Xenopus laevis, Signal Transduction, Gene Expression, Consensus Sequence, Sequence Alignment, Sequence Homology, Amino Acid, In Situ Hybridization, DNA, Complementary, GTP-Binding Proteins, Receptors, Melatonin, Rats
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